1. Moyer VA. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(2):120-134. |
Review/Other-Tx |
N/A |
USPSTF reviewed new evidence on the benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer, as well as the benefits and harms of treatment of localized prostate cancer. |
The USPSTF recommends against PSA-based screening for prostate cancer (grade D recommendation). This recommendation applies to men in the general U.S. population, regardless of age. This recommendation does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer; the use of the PSA test for this indication is outside the scope of the USPSTF. |
4 |
2. Whitmore WF, Jr. Natural history of low-stage prostatic cancer and the impact of early detection. Urol Clin North Am. 1990;17(4):689-697. |
Review/Other-Dx |
N/A |
An expanding and increasingly older population, a rising incidence of prostate cancer, and uncertainties regarding treatment effectiveness have made this disease a target of special concern. The natural history of the cancer must be a consequence of host-tumor interactions, but little is known for sure about this subject. The growth rate of the tumor is determined by many factors, including genetic instability. At present, tumor grade, volume, and ploidy are the most useful techniques for judging the growth rate and metastatic potential. Stage A1 tumors generally are indolent, whereas stage A2 tumors are more aggressive. The natural history of stage B lesions is not well documented. The author asks two questions (Is cure necessary in those in whom it may be possible? Is cure possible in those in whom it may be necessary?) and reviews the problems inherent in screening for prostate cancer at this time. |
No results reported in abstract. |
4 |
3. Ciezki JP, Hsu IC, Abdel-Wahab M, et al. American College of Radiology Appropriateness Criteria((R))--locally advanced (high-risk) prostate cancer. Clin Oncol (R Coll Radiol). 2012;24(1):43-51. |
Review/Other-Tx |
N/A |
Evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for a specific clinical condition. |
n/a |
4 |
4. Bolla M, van Poppel H, Tombal B, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet. 2012;380(9858):2018-2027. |
Experimental-Tx |
1,005 patients |
To report the long-term results of a trial of immediate postoperative irradiation versus a wait-and-see policy in patients with prostate cancer extending beyond the prostate, to confirm whether previously reported progression-free survival was sustained. |
1005 patients were randomly assigned to a wait-and-see policy (n=503) or postoperative irradiation (n=502) and were followed up for a median of 10.6 years (range 2 months to 16.6 years). Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait-and-see policy (198 [39.4%] of 502 patients in postoperative irradiation group vs 311 [61.8%] of 503 patients in wait-and-see group had biochemical or clinical progression or died; HR 0.49 [95% CI 0.41-0.59]; p<0.0001). Late adverse effects (any type of any grade) were more frequent in the postoperative irradiation group than in the wait-and-see group (10 year cumulative incidence 70.8% [66.6-75.0] vs 59.7% [55.3-64.1]; p=0.001). |
1 |
5. Wiegel T, Bottke D, Steiner U, et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol. 2009;27(18):2924-2930. |
Experimental-Tx |
388 patients |
Randomized phase III results of ART vs “wait and see” in patients with pT3 prostate cancer following RP. |
Biochemical control at 5 years increased to 72% for RT arm compared with 54% for wait and see (P=.0015, hazard ratio 0.53). The rate of late grade 3-4 side effects was 0.3%. ART for pT3 prostate cancer significantly reduces the risk of biochemical progression after RP. The rate of side effects is very low. |
1 |
6. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol. 2009;181(3):956-962. |
Experimental-Tx |
425 patients |
Long-term follow-up of a randomized clinical trial of RT to reduce the risk of subsequent metastatic disease and death. 211 men were randomized to observation and 214 to ART. |
Metastasis-free survival was significantly greater with RT (93/214 events on the RT arm vs 114/211 events on observation). Survival improved significantly with ART (88 deaths of 214 on the RT arm vs 110 deaths of 211 on observation). ART after RP for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival. |
1 |
7. Barrett T, Gill AB, Kataoka MY, et al. DCE and DW MRI in monitoring response to androgen deprivation therapy in patients with prostate cancer: a feasibility study. Magn Reson Med. 2012;67(3):778-785. |
Observational-Dx |
23 consecutive patients |
To evaluate 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. |
Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 x 10(-3) mm(2) /s to 1.561 x 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. |
3 |
8. Boorjian SA, Karnes RJ, Viterbo R, et al. Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer. 2011;117(13):2883-2891. |
Observational-Tx |
1238 patients underwent RRP, and 609 patients received with EBRT |
To compare the outcomes after RRP and EBRT for patients who were classified with high-risk prostate cancer according to NCCN criteria |
The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P = .0002). |
2 |
9. Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011;378(9809):2104-2111. |
Experimental-Tx |
1,205 patients assigned (602 in the ADT only group and 603 in the ADT and RT group) |
To assess the role of local RT in addition to ADT in patients with locally advanced prostate cancer. |
Median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small eff ect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). |
1 |
10. Widmark A, Klepp O, Solberg A, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009;373(9660):301-308. |
Experimental-Tx |
875 patients |
Open phase III study comparing endocrine therapy with and without local radiotherapy, followed by castration on progression to assess the effect of radiotherapy. |
After a median follow-up of 7.6 years, 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer. The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9% in the endocrine alone group and 11.9% in the endocrine plus radiotherapy group (difference 12.0%, 95% CI 4.9-19.1%), for a relative risk of 0.44 (0.30-0.66). At 10 years, the cumulative incidence for overall mortality was 39.4% in the endocrine alone group and 29.6% in the endocrine plus radiotherapy group (difference 9.8%, 0.8-18.8%), for a relative risk of 0.68 (0.52-0.89). Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group (74.7%vs 25.9%, p<0.0001; HR 0.16; 0.12-0.20). After 5 years, urinary, rectal, and sexual problems were slightly more frequent in the endocrine plus radiotherapy group. |
1 |
11. The NCCN Clinical Practice Guidelines in Oncology™ Prostate Cancer V.1.2015 © 2015 National Comprehensive Cancer Network, Inc. Available at: http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. |
Review/Other-Tx |
N/A |
To provide guidelines in prostate cancer. |
No abstract available. |
4 |
12. Pilepich MV, Winter K, Lawton CA, et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005;61(5):1285-1290. |
Experimental-Tx |
977 patients; 488 adjuvant arm (Arm I), 489 observation arm (Arm II) |
Randomized phase III trial to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive RT. |
At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs 39%, respectively (P=0.002). The 10-year local failure rate for the adjuvant arm was 23% vs 38% for the control arm (P<0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs 39% (P<0.001) and 16% vs 22% (P=0.0052), respectively, both in favor of the adjuvant arm. |
1 |
13. Roach M, 3rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008;26(4):585-591. |
Experimental-Tx |
456 patients; 224 ADT and EBRT, 232 EBRT alone |
To summarize long-term follow-up results; update the long-term results of RTOG 8610 and confirm the important clinical benefits of adding short-term ADT to EBRT in patients with high-risk, locally advanced disease. |
Ten-year OS estimates (43% vs 34%) and median survival times (8.7 vs 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P=.12). There was a statistically significant improvement in 10-year disease-specific mortality (23% vs 36%; P=.01), distant metastasis (35% vs 47%; P=.006), DFS (11% vs 3%; P<.0001), and biochemical failure (65% v 80%; P<.0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events. The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events. |
1 |
14. Bolla M, Van Tienhoven G, Warde P, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010;11(11):1066-1073. |
Experimental-Tx |
415 total patients; 208 RT alone, 207 combined treatment |
Randomized phase III trial to assess the benefit of the addition of long-term androgen suppression with a luteinizing-hormone-releasing hormone agonist to EBRT in patients with prostate cancer with high metastatic risk. |
Median follow-up was 9·1 years (IQR 5.1-12.6). 10-year clinical DFS was 22.7% (95% CI, 16.3-29.7) in the RT-alone group and 47.7% (39.0-56.0) in the combined treatment group (HR 0.42, 95% CI, 0·33-0·55, P<0.0001). 10-year OS was 39.·8% (95% CI, 31.9-47.5) in patients receiving RT alone and 58.1% (49.2-66.·0) in those allocated combined treatment (HR 0.60, 95% CI, 0.45-0.80, P=0.·0004), and 10-year prostate-cancer mortality was 30.4% (95% CI, 23.2-37.5) and 10.3% (5.1-15.4), respectively (HR 0.38, 95% CI, 0.24-0.60, P<0.0001). In patients with prostate cancer with high metastatic risk, immediate androgen suppression with a luteinizing-hormone-releasing hormone agonist given during and for 3 years after EBRT improves 10-year DFS and OS without increasing late cardiovascular toxicity. |
1 |
15. Zelefsky MJ, Eastham JA, Cronin AM, et al. Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: a comparison of clinical cohorts adjusted for case mix. J Clin Oncol. 2010;28(9):1508-1513. |
Observational-Tx |
2380 patients |
To assess the effect of radical prostatectomy (RP) and external beam radiotherapy (EBRT) on distant metastases (DM) rates in patients with localized prostate cancer treated with RP or EBRT at a single specialized cancer center. |
The 8-year probability of freedom from metastatic progression was 97% for RP patients and 93% for EBRT patients. After adjustment for case mix, surgery was associated with a reduced risk of metastasis (hazard ratio, 0.35; 95% CI, 0.19 to 0.65; P < .001). Results were similar for prostate cancer-specific mortality (hazard ratio, 0.32; 95% CI, 0.13 to 0.80; P = .015). Rates of metastatic progression were similar for favorable-risk disease (1.9% difference in 8-year metastasis-free survival), somewhat reduced for intermediate-risk disease (3.3%), and more substantially reduced in unfavorable-risk disease (7.8% in 8-year metastatic progression). |
2 |
16. Taira AV, Merrick GS, Galbreath RW, et al. Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy. Brachytherapy. 2013;12(5):408-414. |
Observational-Tx |
329 patients |
To report outcomes of men with Gleason grade 5 treated with brachytherapy to help determine the efficacy of brachytherapy in this patient population. |
At 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p=0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p=0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p=0.14). |
2 |
17. Bittner N, Merrick GS, Butler WM, et al. Long-term outcome for very high-risk prostate cancer treated primarily with a triple modality approach to include permanent interstitial brachytherapy. Brachytherapy. 2012;11(4):250-255. |
Observational-Tx |
131 patients |
To evaluate outcome in the most unfavorable subset of high-risk prostate cancer patients treated with a combination of supplemental external beam radiation therapy (EBRT) and brachytherapy. |
The median pretreatment PSA and Gleason score were 11.0ng/mL and 8. One hundred ten (84%) patients had a Gleason score >/=8. At 9 and 12 years, the cause-specific survival, biochemical progression-free survival, and overall survival were 91.0% and 86.5%, 87.3% and 87.3%, and 70.5% and 60.5%, respectively. The most common cause of death was heart disease (22.2%) with deaths from nonprostate cancer (12.7%) and prostate cancer (8.3%) being less likely. |
2 |
18. Stock RG, Cesaretti JA, Hall SJ, Stone NN. Outcomes for patients with high-grade prostate cancer treated with a combination of brachytherapy, external beam radiotherapy and hormonal therapy. BJU Int. 2009;104(11):1631-1636. |
Observational-Tx |
181 patients |
To assess the outcomes for patients with GS 8-10 prostate cancer treated with brachytherapy, EBRT and HT. |
The 8-year actuarial FFbF, freedom from DM, prostate-cancer specific survival and OS were 73%, 80%, 87% and 79%, respectively. The pretreatment PSA level significantly affected FFbF, with 8-year rates of 72%, 82% and 58% for patients with PSA level of =10, >10–20 and >20 ng/mL, respectively (P=0.006). The PSA level had no significant effect on rates of DM. The GS had the most significant affect on FFbF in a multivariate analysis, and was the only factor to significantly affect rates of DM; the 8-year FFbF rates were 84%, 55% and 30% for scores of 8, 9 and 10, respectively (P=0.003). The corresponding freedom from DM and prostate-cancer specific survival rates were 86%, 76%, 30% (P<0.001) and 92%, 80%, 62.5% (P=0.003), respectively. |
2 |
19. Feng FY, Qian Y, Stenmark MH, et al. Perineural invasion predicts increased recurrence, metastasis, and death from prostate cancer following treatment with dose-escalated radiation therapy. Int J Radiat Oncol Biol Phys. 2011;81(4):e361-367. |
Observational-Tx |
651 men |
To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. |
PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. |
2 |
20. Huang J, Vicini FA, Williams SG, et al. Percentage of positive biopsy cores: a better risk stratification model for prostate cancer? Int J Radiat Oncol Biol Phys. 2012;83(4):1141-1148 |
Observational-Tx |
1,056 patients |
To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. |
On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC (</=50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. |
2 |
21. Yamoah K, Stone N, Stock R. Impact of race on biochemical disease recurrence after prostate brachytherapy. Cancer. 2011;117(24):5589-5600. |
Observational-Tx |
2,268 patients |
To examine the influence of race on biochemical disease-free survival (BDFS) among men who received prostate brachytherapy. |
In this series, a total of 2268 patients included 81% Caucasians, 12% African Americans, 6% Hispanics, and 1% Asians. The 10-year actuarial FFbF rate was 70% for AA men and 84% for all others (P = .002). Between Caucasian men and AA men, the 10-year FFbF rate was 83% versus 70%, respectively (P = .001).There was no significant difference in 10-year FFbF between Caucasian men and Hispanic men (83% vs 86%, respectively; P = .6). The 10-year FFbF rate for Hispanic men and AA men was 86% versus 70%, respectively (P = .062). A greater percentage of AA men presented with higher prostate-specific antigen levels (PSA) (>10 ng/mL; 44% vs 21%; P < .001) and, thus, with higher risk disease (24% vs 15%; P < .001) compared with Caucasian men. Among the men with low-risk disease, the 10-year FFbF rate was 90% for Caucasian men and 76% for AA men (P = .041). The 10-year BDFS rate for patients who received brachytherapy alone was 86% for Caucasian men and 61% for AA men (P = .001); however, this difference was not observed when brachytherapy was combined with androgen-deprivation therapy(ADT) with or without supplemental external-beam radiotherapy (EBRT). Multivariate analysis revealed that PSA (P = .024), Gleason score (P < .001), the biologic effective dose (P < .001), EBRT (P = .002), ADT (P = .03), and AA race (P = .037) were significant predictors of 10-year FFbF. No significant differences was observed in overall survival, cause-specific survival, or distant metastasis-free survival between racial groups. |
2 |
22. Jackson W, Hamstra DA, Johnson S, et al. Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy. Cancer. 2013;119(18):3287-3294. |
Observational-Tx |
575 patients |
To review patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution. |
On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001). |
2 |
23. Sabolch A, Feng FY, Daignault-Newton S, et al. Gleason pattern 5 is the greatest risk factor for clinical failure and death from prostate cancer after dose-escalated radiation therapy and hormonal ablation. Int J Radiat Oncol Biol Phys. 2011;81(4):e351-360. |
Observational-Tx |
718 men |
To analyze the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. |
At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. |
2 |
24. Mason MD, Parulekar WR, Sydes MR, et al. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer. J Clin Oncol. 2015:[E-pub ahead of print]. |
Experimental-Tx |
1,205 patients |
To report on the longer-term survival outcomes and toxicity of a randomized trial comparing ADT alone to ADT plut RT. |
One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. |
1 |
25. Lawton CA, DeSilvio M, Roach M, 3rd, et al. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007;69(3):646-655. |
Experimental-Tx |
1,292 patients |
Analysis of the results of the RTOG 94-13 trial. The trial was multicenter prospective randomized and was designed to: 1. Test the hypothesis that total androgen suppression and WPRT followed by a prostate boost improves PFS by =10% compared with total androgen suppression and prostate only RT. 2.Test the hypothesis that NHT followed by concurrent total androgen suppression and RT improves PFS compared with RT followed by AHT by =10%. |
The difference in OS for the four arms was statistically significant (P=0.027). However, no statistically significant differences were found in PFS or OS between NHT vs AHT and WPRT compared with prostate-only RT. A trend towards a difference was found in PFS (P=0.065) in favor of the WPRT + NHT arm compared with the prostate-only RT + NHT and WPRT + AHT arms. |
1 |
26. Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009;360(24):2516-2527. |
Experimental-Tx |
970 randomized to short-term suppression (483) and long term suppression (487) |
Randomized trial to compare the use of RT plus short-term androgen suppression with the use of RT plus long-term androgen suppression in the treatment of locally advanced prostate cancer. |
Median follow-up of 6.4 years. 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed HR was 1.42 (upper 95.71% CI, 1.79; P=0.65 for noninferiority). Combination of RT plus 6 months of androgen suppression provides inferior survival as compared with RT plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. |
1 |
27. D'Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. Jama. 2008;299(3):289-295. |
Experimental-Tx |
206 men |
Randomized trial to compare 6 months of androgen suppression therapy and RT to RT alone and to assess the interaction between level of comorbidity and all-cause mortality. |
Median follow-up was 7.6 years. Addition of 6 months of AST to RT resulted in increased OS in men with localized but unfavorable-risk prostate cancer. |
1 |
28. Denham JW, Steigler A, Lamb DS, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011;12(5):451-459. |
Experimental-Tx |
818 men |
To report results of the TROG 96.01 trial, which assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. |
802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10.6 years (IQR 6.9-11.6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0.72, 95% CI 0.57-0.90; p=0.003) and local progression (0.49, 0.33-0.73; p=0.0005), and improved event-free survival (0.63, 0.52-0.77; p<0.0001). 6 months of NADT further reduced PSA progression (0.57, 0.46-0.72; p<0.0001) and local progression (0.45, 0.30-0.66; p=0.0001), and led to a greater improvement in event-free survival (0.51, 0.42-0.61, p<0.0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0.89, 0.60-1.31; p=0.550), prostate cancer-specific mortality (0.86, 0.60-1.23; p=0.398), or all-cause mortality (0.84, 0.65-1.08; p=0.180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0.49, 0.31-0.76; p=0.001), prostate cancer-specific mortality (0.49, 0.32-0.74; p=0.0008), and all-cause mortality (0.63, 0.48-0.83; p=0.0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation. |
1 |
29. Horwitz EM, Bae K, Hanks GE, et al. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008;26(15):2497-2504. |
Experimental-Tx |
1,554 patients |
To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT). |
Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms. At 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P |
1 |
30. Zapatero A, Guerrero A, Maldonado X, et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16(3):320-327. |
Experimental-Tx |
355 patients |
To determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. |
Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1.88 [95% CI 1.12-3.15]; p=0.01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2.48 [95% CI 1.31-4.68]; p=0.009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2.31 [95% CI 1.23-3.85]; p=0.01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. |
1 |
31. Pisansky TM, Suman VJ, Roach M, 3rd, Sandler HM. Reporting of results in DART01/05 GICOR. Lancet Oncol. 2015;16(6):e258. |
Review/Other-Tx |
N/A |
No abstract available. |
No abstract available. |
4 |
32. Nabid A, Carrier N, Martin A-G, et al. High-risk prostate cancer treated with pelvic radiotherapy and 36 versus 18 months of androgen blockade: Results of a phase III randomized study. ASCO Meeting Abstracts. 2013;31(6_suppl):3. |
Experimental-Tx |
630 patients |
To compare outcomes between 36 vs. 18 months of AB in high risk prostate cancer treated with RT. |
From October 2000 to January 2008, 310 patients were randomized to arm 1 and 320 to arm 2. Patients’ characteristics were well balanced between the two arms (median age 71 years, median PSA 16 ng/ml, median Gleason score 8). Most patients had T2-3 disease. At a median follow-up of 77 months, 71/310 patients (22.9%) in arm 1 and 76/320 (23.8%) in arm 2 had died (p=0.802). Overall, 116 patients died of causes other than prostate cancer. Overall and cancer specific survival hazard ratios were 1.15 (0.83-1.59), p=0.398 and 1.13 (0.61-2.08), p=0.153, respectively. 5 year overall and disease specific survival rates were 92.1% (89.1-95.1) vs. 86.8% (83.0-90.6), p=0.052 and 97.6% (95.9-99.4) vs. 96.4% (94.2-98.6), p=0.473 and 10 year overall and disease specific survival rates were 63.6% (55.7-71.5) vs. 63.2% (54.7-71.7), p=0.429 and 87.2% (81.0-93.3) vs. 87.2% (80.9-93.6), p=0.838 for arm 1 and arm 2, respectively. There were no significant differences in the rates of biochemical, regional or distant failure between arms. |
1 |
33. Pommier P, Chabaud S, Lagrange JL, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol. 2007;25(34):5366-5373. |
Experimental-Tx |
446 patients |
Review of a randomized multicenter open phase III trial to assess the benefit and toxicity and QoL outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients. Patients were randomly assigned to either pelvic and prostate RT or prostate RT only. |
With a 42.1-month median follow-up time, the 5-year PFS and OS were similar in the two treatment arms for the whole series and for each stratified group. On multivariate analysis, low LNI risk and hormonal therapy were statistically associated with increased PFS. However, subgroup analyses based on these factors did not show any benefit for pelvic irradiation. There were no significant differences in acute and late digestive toxicities and in QoL outcomes. |
1 |
34. Rusthoven CG, Carlson JA, Waxweiler TV, et al. The impact of definitive local therapy for lymph node-positive prostate cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2014;88(5):1064-1073. |
Observational-Tx |
796 cN+ and 2,991 pN+ patients |
To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (RP, EBRT, or both) vs no local therapy in the U.S. population in the modern PSA era. |
A total of 796 cN+ and 2,991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had no local therapy. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% vs 29% (P<.001) and prostate cancer-specific survival rates of 67% vs 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had no local therapy. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% vs 42% (P<.001) and prostate cancer-specific survival rates of 78% vs 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and prostate cancer-specific survival (all P<.001). Local therapy was associated with favorable HRs across subgroups, including patients aged =70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP vs EBRT and RP with or without adjuvant EBRT. |
2 |
35. Johnstone PA, Assikis V, Goodman M, Ward KC, Riffenburgh RH, Master V. Lack of survival benefit of post-operative radiation therapy in prostate cancer patients with positive lymph nodes. Prostate Cancer Prostatic Dis. 2007;10(2):185-188. |
Observational-Tx |
1,921 patients |
To provide for informed decisions as to whether RT post-RP benefits the +LN patient. |
Specifically analyzed were data for 1921 patients with nonmetastatic prostate cancer who underwent surgery alone, or surgery followed by RT, and who had +LNs documented. SEER does not code the interval between surgery and RT, so the ratio of patients receiving salvage versus adjuvant therapy is unknown. Using follow-up data through 2002, post-diagnosis survival was examined by number of +LNs. There was no significant relative survival benefit for +LN patients receiving post-operative RT (chi(2)P=0.270). |
2 |
36. Briganti A, Karnes RJ, Da Pozzo LF, et al. Combination of adjuvant hormonal and radiation therapy significantly prolongs survival of patients with pT2-4 pN+ prostate cancer: results of a matched analysis. Eur Urol. 2011;59(5):832-840. |
Observational-Tx |
703 patients |
To assess the impact of combination adjuvant HT and RT on the survival of patients with prostate cancer and histologically documented lymph node metastases (pN+). |
Following the matching process, 117 pT2-4 pN1 patients of 171 (68.4%) treated with adjuvant HT plus RT (group 1) were compared with 247 pT2-4 pN1 patients of 532 (46.4%) receiving adjuvant HT alone (group 2). After matching, the 2 groups of patients were comparable in terms of pre- and postoperative characteristics (all P=0.07). Mean follow-up was 100.8 mo (median: 95.1 mo; range: 3.5–229.3 mo). Overall, prostate CSS and OS rates at 5, 8, and 10 years were 90%, 82%, and 75%, and 85%, 70%, and 60%, respectively. Patients treated with adjuvant RT plus HT had significantly higher CSS and OS rates compared with patients treated with HT alone at 5, 8, and 10 years after surgery (95%, 91%, and 86% vs 88%, 78%, and 70%, and 90%, 84%, and 74% vs 82%, 65%, and 55%, respectively; P=0.004 and P<0.001, respectively). Similarly, higher survival rates associated with the combination of HT plus RT were found when patients were stratified according to the extent of nodal invasion (namely, 2 or fewer vs more than 2 positive nodes; all P= 0.006). Lack of standardized HT and RT protocols represents the main limitations of our retrospective study. |
2 |
37. Abdollah F, Karnes RJ, Suardi N, et al. Impact of adjuvant radiotherapy on survival of patients with node-positive prostate cancer. J Clin Oncol. 2014;32(35):3939-3947. |
Observational-Tx |
1,107 patients |
To test the hypothesis that the impact of adjuvant RT on cancer-specific mortality in patients with pN1 prostate cancer is related to tumor characteristics. |
Overall, 35% of patients received adjuvant RT. At multivariable analysis, adjuvant RT was associated with more favorable cancer-specific mortality rate (HR, 0.37; P<.001). However, when patients were stratified into risk groups, only 2 groups of men benefited from adjuvant RT: (1) patients with positive lymph node count =2, Gleason score 7 to 10, pT3b/pT4 stage, or positive surgical margins (HR, 0.30; P=.002); and (2) patients with positive lymph node count of 3 to 4 (HR, 0.21; P=.02), regardless of other tumor characteristics. These results were confirmed when overall mortalitywas examined as an end point. |
2 |
38. Kuban DA, Tucker SL, Dong L, et al. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70(1):67-74. |
Experimental-Tx |
301 patients |
To report the long-term results of a randomized RT dose escalation trial for prostate cancer. |
For all patients, freedom from biochemical or clinical failure was superior for the 78 Gy arm, 78%, as compared with 59% for the 70 Gy arm (P=0.004, and an even greater benefit was seen in patients with initial PSA >10 ng/ml (78% vs 39%, P=0.001). Clinical failure rate was significantly reduced in the 78 Gy arm as well (7% vs 15%, P=0.014). |
1 |
39. Spratt DE, Pei X, Yamada J, Kollmeier MA, Cox B, Zelefsky MJ. Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2013;85(3):686-692. |
Experimental-Tx |
1,002 patients; 587 patients treated with neoadjuvant and concurrent androgen-deprivation therapy. |
To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. |
For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up |
2 |
40. Arcangeli S, Strigari L, Gomellini S, et al. Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1172-1178. |
Experimental-Tx |
168 patients |
To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high-risk prostate cancer. |
In a median follow-up of 70 months, biochemical failure (BF) occurred in 35 of the 168 patients (21%) in the study. Among these 35 patients, local failure (LF) only was detected in 11 (31%), distant failure (DF) only in 16 (46%), and both LF and DF in 6 (17%). In 2 patients (6%) BF has not yet been clinically detected. The risk reduction by hypofractionation was significant in BF (10.3%) but not in LF and DF. We found that hypofractionation, with respect to conventional fractionation, determined only an insignificant increase in the actuarial FFBF but no difference in FFLF and FFDF, when considering the entire group of patients. However, an increase in the 5-year rates in all 3 endpoints-FFBF, FFLF, and FFDF-was observed in the subgroup of patients with a pretreatment prostate-specific antigen (iPSA) level of 20 ng/mL or less. On multivariate analysis, the type of fractionation, iPSA level, Gleason score of 4+3 or higher, and T stage of 2c or higher have been confirmed as independent prognostic factors for BF. High iPSA levels and Gleason score of 4+3 or higher were also significantly associated with an increased risk of DF, whereas T stage of 2c or higher was the only independent variable for LF. |
1 |
41. Patel AR, Sandler HM, Pienta KJ. Radiation Therapy Oncology Group 0521: a phase III randomized trial of androgen suppression and radiation therapy versus androgen suppression and radiation therapy followed by chemotherapy with docetaxel/prednisone for localized, high-risk prostate cancer. Clin Genitourin Cancer. 2005;4(3):212-214. |
Review/Other-Tx |
N/A |
To assess the relative efficacy of the combination of AS with RT followed by AS versus AS with RT followed by docetaxel/prednisone along with AS in a population of patients with clinically localized prostate cancer with unfavorable prognostic factors. |
No results reported in abstract. |
4 |
42. Rosenthal SA, Bae K, Pienta KJ, et al. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02. Int J Radiat Oncol Biol Phys. 2009;73(3):672-678. |
Experimental-Tx |
381 patients: 192 – Arm 1; 189 – Arm 2 |
To determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide plus AST + RT would improve disease outcomes with acceptable toxicity. |
136 Arm 2 patients (71%) had RTOG Grade 3 or greater toxicity compared with 70 Arm 1 patient (37%). Statistically significant increases in hematologic toxicity (P<0.0001) and gastrointestinal toxicity (P=0.017) but not genitourinary toxicity (P=0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. Paclitaxel, estramustine, and etoposide were associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer. |
1 |
43. Kupelian PA, Potters L, Khuntia D, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys. 2004;58(1):25-33. |
Observational-Tx |
2,991 patients |
To review the biochemical relapse-free survival (bRFS) rates after treatment with permanent seed implantation (PI), external beam radiotherapy (EBRT) <72 Gy (EBRT <72), EBRT > or =72 Gy (EBRT > or =72), combined seeds and EBRT (COMB), or radical prostatectomy (RP) for clinical Stage T1-T2 localized prostate cancer treated between 1990 and 1998. |
The 5-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 81%, 51%, 81%, 83%, and 77%, respectively (p <0.001). The 7-year bRFS rate for RP, EBRT <72, EBRT > or =72, PI, and COMB was 76%, 48%, 81%, 75%, and 77%, respectively. Multivariate analysis, including all cases, showed iPSA (p <0.001), bGS (p <0.001), year of therapy (p <0.001), and treatment modality (p <0.001) to be independent predictors of relapse. Because EBRT <72 cases had distinctly worse outcomes, the analysis was repeated after excluding these cases to discern any differences among the other modalities. The multivariate analysis excluding the EBRT <72 cases revealed iPSA (p <0.001), bGS (p <0.001), and year of therapy (p = 0.001) to be the only independent predictors of relapse. Treatment modality (p = 0.95), clinical T stage (p = 0.09), and androgen deprivation (p = 0.56) were not independent predictors for failure. |
2 |
44. Westover K, Chen MH, Moul J, et al. Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer. BJU Int. 2012;110(8):1116-1121. |
Observational-Tx |
657 patients |
To assess the risk of prostate cancer-specific mortality after therapy with radical prostatectomy (RP) or combined-modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen-suppression therapy (AST) in men with Gleason score 8-10 prostate cancer. |
As of January 2009, with a median (interquartile range) follow-up of 4.62 (2.4-8.2) years, there were 21 prostate cancer-specific deaths. Treatment with RP was not associated with an increased risk of prostate cancer-specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6-5.6, P = 0.3). Factors associated with an increased risk of prostate cancer-specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3-16, P < 0.001) as compared with >/=4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1-7.2; P = 0.03) as compared with T1c, 2a. |
2 |
45. Aizer AA, Yu JB, Colberg JW, McKeon AM, Decker RH, Peschel RE. Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma. Radiother Oncol. 2009;93(2):185-191. |
Observational-Tx |
556 patients RP (n=204) or IMRT (n=352) |
To determine whether RP or IMRT to =72 Gy, plus hormonal therapy if indicated, results in improved BDFS in localized prostate adenocarcinoma. |
IMRT patients had more advanced disease at baseline (p<.001). There was no difference in five-year BDFS rates between RP and IMRT in the favorable (92.8% vs. 85.3%, p=.20) or intermediate prognosis (86.7% vs. 82.2%, p=.46) subsets. A difference favoring IMRT plus hormonal therapy was seen in the poor prognosis (38.4% vs. 62.2%, p<.001) subset. Within the entire cohort, after adjustment for confounding variables, Gleason score (p<.001) and clinical stage (p<.001) predicted BDFS, but treatment modality (p=.06) did not. Within the poor prognosis subset, treatment modality (p=.006) predicted BDFS. |
2 |
46. Ellis CL, Partin AW, Han M, Epstein JI. Adenocarcinoma of the prostate with Gleason score 9-10 on core biopsy: correlation with findings at radical prostatectomy and prognosis. J Urol. 2013;190(6):2068-2073. |
Observational-Tx |
259 men |
To report the largest study to date to specifically analyze the correlation of Gleason score 9-10 on needle core biopsy with radical prostatectomy outcomes. |
Statistically significant predictors of radical prostatectomy outcome were organ confinement (total cores with Gleason score 9-10, maximum percent overall and perineural invasion), margin status (preoperative prostate specific antigen and clinical stage), seminal vesicle invasion (maximum percent overall, perineural invasion and clinical stage), lymph node metastasis (total number of cores with Gleason score 9-10 and clinical stage) and biochemical-free survival (maximum percent of Gleason score 9-10, maximum percent overall and clinical stage) (each p<0.05). |
2 |
47. Cooperberg MR, Vickers AJ, Broering JM, Carroll PR. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. Cancer. 2010;116(22):5226-5234. |
Observational-Tx |
7,538 patients |
To analyze risk-adjusted, cancer-specific mortality outcomes among men who underwent radical prostatectomy, men who received external-beam radiation therapy, and men who received primary androgen-deprivation therapy. |
In total, 266 men died of prostate cancer during follow-up. Adjusting for age and risk, the hazard ratio for cancer-specific mortality relative to prostatectomy was 2.21 (95% confidence interval [CI], 1.50-3.24) for radiation therapy and 3.22 (95% CI, 2.16-4.81) for androgen deprivation. Absolute differences between prostatectomy and radiation therapy were small for men at low risk but increased substantially for men at intermediate and high risk. These results were robust to a variety of different analytic techniques, including competing risks regression analysis, adjustment by CAPRA score rather than Kattan score, and examination of overall survival as the endpoint. |
2 |
48. Hoffman RM, Koyama T, Fan KH, et al. Mortality after radical prostatectomy or external beam radiotherapy for localized prostate cancer. J Natl Cancer Inst. 2013;105(10):711-718. |
Observational-Tx |
1,164 RP patients; 491 EBRT patients |
To estimate the association of radical prostatectomy (compared with EBRT) with overall and prostate cancer mortality |
After 15 years of follow-up, there were 568 deaths, including 104 from PC. RP was associated with statistically significant advantages for overall (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.53 to 0.70, P <.0001.) and disease-specific mortality (HR = 0.35, 95% CI = 0.26 to 0.49, P <.0001.). Mortality benefits for RP were also observed within treatment propensity quintiles, when subjects were pair-matched on propensity scores, and in subgroup analyses based on age, tumor characteristics, and comorbidity. |
2 |
49. Kibel AS, Ciezki JP, Klein EA, et al. Survival among men with clinically localized prostate cancer treated with radical prostatectomy or radiation therapy in the prostate specific antigen era. J Urol. 2012;187(4):1259-1265. |
Observational-Tx |
10,429 patients |
To analyze the survival of patients treated with radical prostatectomy, external beam radiotherapy and brachytherapy according to contemporary standards |
The adjusted 10-year overall survival after radical prostatectomy, external beam radiotherapy and brachytherapy was 88.9%, 82.6% and 81.7%, respectively. Adjusted 10-year prostate cancer specific mortality was 1.8%, 2.9% and 2.3%, respectively. Using propensity score analysis, external beam radiotherapy was associated with decreased overall survival (HR 1.6, 95% CI 1.4-1.9, p<0.001) and increased prostate cancer specific mortality (HR 1.5, 95% CI 1.0-2.3, p=0.041) compared to radical prostatectomy. Brachytherapy was associated with decreased overall survival (HR 1.7, 95% CI 1.4-2.1, p<0.001) but not prostate cancer specific mortality (HR 1.3, 95% CI 0.7-2.4, p=0.5) compared to radical prostatectomy. |
2 |
50. Nepple KG, Stephenson AJ, Kallogjeri D, et al. Mortality after prostate cancer treatment with radical prostatectomy, external-beam radiation therapy, or brachytherapy in men without comorbidity. Eur Urol. 2013;64(3):372-378. |
Observational-Tx |
6,692 patients |
To evaluate PCM and OM in men with no recorded comorbidity treated with radical prostatectomy (RP), external-beam radiation therapy (EBRT), or brachytherapy (BT). |
Using Cox analysis, EBRT was associated with an increase in PCM compared with RP (hazard ratio [HR]: 1.66; 95% confidence interval [CI], 1.05-2.63), while there was no statistically significant increase with BT (HR: 1.83; 95% CI, 0.88-3.82). Using competing risks analysis, the benefit of RP remained but was no longer statistically significant for EBRT (HR: 1.55; 95% CI, 0.92-2.60) or BT (HR: 1.66; 95% CI, 0.79-3.46). In comparison with RP, both EBRT (HR: 1.71; 95% CI, 1.40-2.08) and BT (HR: 1.78; 95% CI, 1.37-2.31) were associated with increased OM. |
2 |
51. Sooriakumaran P, Nyberg T, Akre O, et al. Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes. BMJ. 2014;348:g1502. |
Observational-Tx |
34,515 patients |
To compare the survival outcomes of patients treated with surgery or radiotherapy for prostate cancer. |
Prostate cancer mortality became a larger proportion of overall mortality as risk group increased for both the surgery and the radiotherapy cohorts. Among patients with non-metastatic prostate cancer the adjusted subdistribution hazard ratio for prostate cancer mortality favoured surgery (1.76, 95% confidence interval 1.49 to 2.08, for radiotherapy v prostatectomy), whereas there was no discernible difference in treatment effect among men with metastatic disease. Subgroup analyses indicated more clear benefits of surgery among younger and fitter men with intermediate and high risk disease. Sensitivity analyses confirmed the main findings. |
2 |
52. Briganti A, Joniau S, Gontero P, et al. Identifying the best candidate for radical prostatectomy among patients with high-risk prostate cancer. Eur Urol. 2012;61(3):584-592. |
Observational-Tx |
1,366 patients |
To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. |
Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p |
2 |
53. Gustafson GS, Nguyen PL, Assimos DG, et al. ACR Appropriateness Criteria(R) Postradical Prostatectomy Irradiation in Prostate Cancer. Oncology (Williston Park). 2014;28(12). |
Review/Other-Tx |
N/A |
Evidence-based guidelines to assist referring physicians and other providers in making the most appropriate treatment decisions for postradical prostatectomy irradiation in prostate cancer. |
N/A |
4 |
54. Grimm P, Billiet I, Bostwick D, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int. 2012;109 Suppl 1:22-29. |
Review/Other-Tx |
N/A |
A comprehensive review of the literature comparing risk stratified patients by treatment option and with long-term follow-up. |
A statistical analysis (standard deviational ellipse) of the study outcomes suggested that, in terms of biochemical-free progression, brachytherapy provides superior outcome in patients with low-risk disease. For intermediate-risk disease, the combination of EBRT and brachytherapy appears equivalent to brachytherapy alone. For high-risk patients, combination therapies involving EBRT and brachytherapy plus or minus androgen deprivation therapy appear superior to more localized treatments such as seed implant alone, surgery alone or EBRT. |
4 |
55. Shilkrut M, Merrick GS, McLaughlin PW, et al. The addition of low-dose-rate brachytherapy and androgen-deprivation therapy decreases biochemical failure and prostate cancer death compared with dose-escalated external-beam radiation therapy for high-risk prostate cancer. Cancer. 2013;119(3):681-690. |
Observational-Tx |
958 patients |
To determine whether the addition of low-dose-rate brachytherapy or androgen-deprivation therapy (ADT) improves clinical outcome in patients with high-risk prostate cancer (HiRPCa) who received dose-escalated radiotherapy (RT). |
The median follow-up was 63.2 months (interquartile range, 35.4-99.0 months), and 250 patients were followed for >8 years. Compared with CMRT, patients who received EBRT had higher prostate-specific antigen levels, higher tumor classification, lower Gleason sum, and more frequent receipt of ADT for a longer duration. The 8-year incidence BF and PCSM among patients who received EBRT was 40% (standard error, 38%-44%) and 13% (standard error, 11%-15%) compared with 14% (standard error, 12%-16%; P < .0001) and 7% (standard error 6%-9%; P = .003) among patients who received CMRT. On multivariate analysis, the hazard ratios (HRs) for BF and PCSM were 0.35 (95% confidence interval [CI], 0.23-0.52; P < .0001) and 0.41 (95% CI, 0.23-0.75; P < .003), favoring CMRT. Increasing duration of ADT predicted decreased BF (P = .04) and PCSM (P = .001), which was greatest with long-term ADT (BF: HR, 0.33; P < .0001; 95% CI, 0.21-0.52; PCSM: HR, 0.30; P = .001; 95% CI, 0.15-0.6) even in the subgroup that received CMRT. |
2 |
56. Taira AV, Merrick GS, Galbreath RW, et al. Distant metastases following permanent interstitial brachytherapy for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):e225-232. |
Observational-Tx |
1,840 consecutive patients |
To compare metastases-free survival (MFS) or CSS between men treated with RP versus those treated with brachytherapy in a consecutive cohort of patients undergoing permanent interstitial brachytherapy. |
For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. |
2 |
57. Merrick GS, Butler WM, Galbreath RW, et al. Prostate cancer death is unlikely in high-risk patients following quality permanent interstitial brachytherapy. BJU Int. 2011;107(2):226-232. |
Observational-Tx |
284 patients |
To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in high-risk prostate cancer brachytherapy patients. |
Twelve-year CSS, bPFS and OS were 94.2%, 89.0% and 69.7%. On multivariate analysis, bPFS was best predicted by percent positive biopsies and ADT. The analysis failed to identify any predictors for CSS, while OS was highly correlated with patient age, percent positive biopsies and diabetes. Fourteen percent of patients died from diseases of the heart, while 8%, 8% and 6% of patients died from non-prostate cancer, other causes and prostate cancer, respectively. When OS was stratified by patients with 0-3 vs >/= 4 comorbidities, the 12-year OS was 73.0% and 52.7% (P = 0.036). |
2 |
58. Morris WJ, Tyldesley S, Pai HH, et al. ASCENDE-RT*: A multicenter, randomized trial of dose-escalated external beam radiation therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorable-risk localized prostate cancer. J Clin Oncol. 2015;33:(suppl 7; abstr 3). |
Experimental-Tx |
398 patients |
To compare the efficacy of DE-EBRT and LDR-B for National Comprehensive Cancer Network (NCCN) high and intermediate-risk disease. |
Between Dec 2002 and Sep 2011, 276 high-risk and 122 intermediate-risk patients were accrued at 6 cancer treatment centers. 200 men were assigned to DE-EBRT and 198 to LDR-B. The treatment arms were well balanced in terms of age and known prognostic factors. Median follow up (FU) is 6.5 years; 65 men have >9 years FU. There were 12 major protocol violations in each arm. By intent-to-treat analysis, the 3-, 5-, 7-, and 9-year Kaplan-Meier RFS estimates are 94% vs 94%, 77% vs 89%, 71% vs 86%, and 63% vs 83% for DE-EBRT and LDR-B respectively (hazard ratio = 0.473; 95% CI 0.292 – 0.765; P = 0.0022). Randomization (p<0.001), percent positive cores (p=0.005), initial PSA (p=0.006) and clinical T-stage (p=0.013) were predictive of RFS in a multivariable Cox model. The median PSA at latest FU for non-relapsing patients assigned to LDR-B is 0.02 vs 0.24 ng/mL for DE-EBRT. |
1 |
59. D'Amico AV, Moran BJ, Braccioforte MH, et al. Risk of death from prostate cancer after brachytherapy alone or with radiation, androgen suppression therapy, or both in men with high-risk disease. J Clin Oncol. 2009;27(24):3923-3928. |
Observational-Tx |
1,342 men |
To estimate the risk of prostate cancer (PC) -specific mortality (PCSM) after brachytherapy alone or in conjunction with androgen suppression therapy (AST), external-beam radiation therapy (EBRT), or both in men with high-risk PC. |
Despite higher baseline probabilities of PCSM after a median follow-up of 5.1 years, there was a significant reduction in the risk of PCSM (adjusted hazard ratio [AHR], 0.32; 95% CI, 0.14 to 0.73; P = .006) in men treated with brachytherapy and both AST and EBRT as compared with neither. When compared with brachytherapy alone, a significant decrease in the risk of PCSM was not observed in men treated with either supplemental AST (AHR, 0.63; 95% CI, 0.27 to 1.47; P = .28) or EBRT (AHR, 0.57; 95% CI, 0.21 to 1.52; P = .26). There was a near-significant reduction (AHR, 0.53; 95% CI, 0.27 to 1.07; P = .079) in the risk of PCSM in men treated with tri- as compared with bimodality therapy. |
2 |
60. Deutsch I, Zelefsky MJ, Zhang Z, et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy. 2010;9(4):313-318. |
Observational-Tx |
630 total patients |
To report on a retrospective comparison of biochemical outcomes using an ultra-high dose of conventionally fractionated intensity-modulated radiation therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR) brachytherapy to increase the biologically effective dose of IMRT. |
The 5-year actuarial PSA relapse-free survival (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%, and 93% vs. 71%, for National Comprehensive Cancer Network low- (p=0.71), intermediate- (p<0.001), and high-risk (p=0.23) groups, respectively. Treatment (p=0.0006), T stage (p<0.0001), Gleason score (p<0.0001), pretreatment PSA (p=0.0037), risk group (p<0.0001), and lack of androgen-deprivation therapy (p=0.0005) were significantly associated with improved PRFS on univariate analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p=0.0012, hazard ratio [HR]=0.184); age (p=0.0222, HR=0.965); and risk group (p<0.0001, HR=2.683) were associated with improved PRFS on multivariate analysis. |
2 |
61. Hoffman KE, Chen MH, Moran BJ, et al. Prostate cancer-specific mortality and the extent of therapy in healthy elderly men with high-risk prostate cancer. Cancer. 2010;116(11):2590-2595. |
Observational-Tx |
764 patients; 206 received brachytherapy alone; 558 received androgen-suppression therapy |
Compare the use of brachytherapy alone with combined brachytherapy, EBRT to the prostate and seminal vesicles, and androgen-suppression therapy in a population of healthy elderly men. |
After adjusting for age and prostate cancer prognostic factors, risk of prostate cancer-specific mortality was significantly less for men who received androgen-suppression therapy than those receiving brachytherapy alone. Other factors associated significantly with an increased risk of prostate cancer-specific mortality included GS of 8-10. Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had lower risk of prostate cancer-specific mortality when they received androgen-suppression therapy than brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. |
2 |
62. Cohen JK, Miller RJ, Jr., Ahmed S, Lotz MJ, Baust J. Ten-year biochemical disease control for patients with prostate cancer treated with cryosurgery as primary therapy. Urology. 2008;71(3):515-518. |
Observational-Tx |
370 patients |
To report the long-term biochemical and biopsy follow-up for a cohort of patients who had undergone prostate cryosurgery as primary treatment of prostate adenocarcinoma. |
The median follow-up was 12.55 years. Using a nadir plus 2 ng/dL definition, Kaplan-Meier analysis demonstrated a biochemical disease-free survival rate at 10 years of 80.56%, 74.16%, and 45.54% for low, moderate, and high-risk groups, respectively. The 10-year negative biopsy rate was 76.96%. |
2 |
63. Merrick GS, Wallner KE, Butler WM. Prostate cryotherapy: more questions than answers. Urology. 2005;66(1):9-15. |
Review/Other-Tx |
N/A |
No abstract available. |
No abstract available. |
4 |
64. Uchida T, Shoji S, Nakano M, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16(11):881-886. |
Observational-Tx |
517 patients |
To report on the long-term results of high-intensity focused US in the treatment of localized prostate cancer. |
Median follow-up period for all patients was 24 months. BDFR in all patients at 5 years was 72%. BDFR in patients with stage T1c, T2a, T2b, T2c and T3 groups at 5 years were 74%, 79%, 72%, 24% and 33%, respectively (P<0.0001). BDFR in patients in the low, intermediate and high-risk groups at 5 years were 84%, 64% and 45%, respectively (P<0.0001). BDFR in patients treated with or without NHT at 7 years were 73% and 53% (P<0.0001), respectively. Pretreatment PSA levels (HR 1.060; P<0.0001; 95% CI 1.040-1.080), NHT (HR 2.252; P<0.0001; 95% CI 1.530-3.315) and stage (P=0.0189) were demonstrated to be statistically significant variables. |
2 |
65. Thuroff S, Chaussy C. Evolution and outcomes of 3 MHz high intensity focused ultrasound therapy for localized prostate cancer during 15 years. J Urol. 2013;190(2):702-710. |
Observational-Tx |
704 patients |
To describe the long-term cancer control and morbidity of high intensity focused ultrasound with neoadjuvant transurethral resection of the prostate, the risk of metastatic induction by transurethral prostate resection, and the evolution of high intensity focused ultrasound application and technology with time. |
Of 704 study patients 78.5% had intermediate or high risk disease. Mean followup was 5.3 years (range 1.3 to 14). Cancer specific survival was 99%, metastasis-free survival was 95%, and 10-year salvage treatment-free rates were 98% in low risk, 72% in intermediate risk and 68% in high risk patients. Prostate specific antigen nadir and Gleason score predicted biochemical failure, and side effects were moderate. The high intensity focused ultrasound re-treatment rate has been 15% since 2005. |
1 |
66. Ellis DS, Manny TB, Jr., Rewcastle JC. Cryoablation as primary treatment for localized prostate cancer followed by penile rehabilitation. Urology. 2007;69(2):306-310. |
Observational-Tx |
416 patients |
To determine the medium term efficacy and morbidity of patients who underwent cryoablation as primary therapy for localized prostate cancer followed by a penile rehabilitation regimen. |
A total of 416 consecutive patients were treated. The mean patient age was 69.4 years, mean prostate-specific antigen level was 8.7 ng/mL, median Gleason score was 6, and median stage was T1c. The mean follow-up of the entire population was 20.4 +/- 14.7 months. Of those continent before treatment, 4.0% were incontinent at 6 months but only 2 (0.6%) used any absorbent pads. Kaplan-Meier analysis demonstrated progressive recovery of sexual function of preoperatively potent men, with 41.4% +/- 4.3% and 51.3% +/- 5.9% potent 1 and 4 years after treatment, respectively. No patients had rectal fistula. The actuarial probability of remaining biochemically disease free at 4 years was 79.6% +/- 2.4%, with a mean time to failure of 4.2 months. After therapy, 168 patients underwent biopsy; 17 had positive findings (10.1%). The positive biopsy rate for the entire population was 4.1% (17 of 416). |
2 |
67. Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011;365(2):107-118. |
Experimental-Tx |
1,979 patients |
To evaluate whether adding short-term ADT to radiotherapy would improve survival among patients with nonbulky localized prostate adenocarcinomas and an initial PSA level of 20 ng per milliliter or less. |
The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. |
1 |
68. Laverdiere J, Gomez JL, Cusan L, et al. Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys. 1997;37(2):247-252. |
Experimental-Tx |
120 patients |
To investigate whether combined androgen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of positive follow-up biopsies and serum PSA compared to radiation therapy alone. |
Ninety-two and 68 patients underwent biopsies at 12 and 24 months, respectively, after the end of radiation therapy. While 62% of control patients at 12 months in Group 1 disclosed residual neoplasm, only 30% and 4% showed residual disease in groups 2 and 3, respectively (p = 0.00005). When looking at 24 months, 65, 28, and 5% showed residual cancer for groups 1, 2, and 3, respectively (p = 0.00001). The PSA measurements indicate also at 12 months a difference between the three groups (p < 0.0001), except at 24 months, the difference between the group 2 and 3 is no longer significant. |
1 |
69. Gleave ME, Goldenberg SL, Chin JL, et al. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol. 2001;166(2):500-506; discussion 506-507. |
Experimental-Tx |
547 patients stratified for T stage, Gleason grade, and pretreatment PSA |
Prospective phase III, open label randomized controlled multicenter trial to determine whether 8-month compared with 3-month NHT reduces PSA recurrence rates after RP. Interim analysis shows secondary end points, including differences in biochemistry, pathology and adverse events between the 2 groups. |
Men in 8-month group noticed higher number of newly reported adverse events (4.5 vs 2.9, P<0.0001) and higher incidence of hot flushes than 3-month group (87% vs 72%, respectively, P<0.0001). Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of NHT, suggesting that the optimal duration of NHT is longer than 3 months. Longer follow-up is needed to determine whether longer therapy alters PSA recurrence rates. |
1 |
70. Zelefsky MJ, Reuter VE, Fuks Z, Scardino P, Shippy A. Influence of local tumor control on distant metastases and cancer related mortality after external beam radiotherapy for prostate cancer. J Urol. 2008;179(4):1368-1373; discussion 1373. |
Observational-Tx |
339 patients |
To report local control outcomes, as assessed by posttreatment biopsies in patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer and to report the influence of local tumor control on long-term distant metastases and cause specific survival outcomes. |
Overall biopsy outcomes in these patients were positive in 32%, severe treatment effect in 21% and negative in 47%. A higher radiation dose in the intermediate and high risk subgroups was associated with a lower incidence of positive biopsy. Of patients at intermediate risk who received a dose of 75.6 or greater 24% had a positive biopsy compared to 42% who received 70.2 Gy or less (p = 0.03). In the high risk group positive treatment biopsies were noted in 51% of patients who received 70.2 Gy or less, 33% of those who received 75.6 Gy and 15% of those who received 81 Gy or greater (70.2 or less vs 75.6 Gy p = 0.07 and 75.6 vs 81 Gy or greater p = 0.05). Short course neoadjuvant androgen deprivation therapy before 3-dimensional conformal radiotherapy had a significant impact on the posttreatment biopsy outcome. Of patients who did not receive androgen deprivation therapy 42% had a positive biopsy compared to 16% who received androgen deprivation therapy (p <0.0001). Patients with negative and severe treatment effect biopsies had similar 10-year prostate specific antigen relapse-free survival outcomes that were markedly different from outcomes in those with positive treatment biopsies. Multivariate analysis indicated that the strongest predictor of biochemical failure was posttreatment biopsy status (positive vs severe treatment effect or negative p <0.001), followed by pretreatment prostate specific antigen (p = 0.05) and clinical T stage (p = 0.09). Similarly multivariate analysis revealed that a positive posttreatment biopsy was one of the strongest predictors of distant metastasis and prostate cancer death in this cohort of patients. |
2 |
71. Pardo Y, Guedea F, Aguilo F, et al. Quality-of-life impact of primary treatments for localized prostate cancer in patients without hormonal treatment. J Clin Oncol. 2010;28(31):4687-4696. |
Observational-Tx |
435 patients |
To compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment. |
Compared with the brachytherapy group, the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results (-18.22, -13.19, and +6.38, respectively, at 3 years; P < .001). In patients with urinary irritative-obstructive symptoms at baseline, improvement was observed in 64% of those treated with nerve-sparing radical prostatectomy. Higher bowel worsening (-2.87, P = .04) was observed in the external radiotherapy group, with 20% of patients reporting bowel symptoms. |
1 |
72. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008;358(12):1250-1261. |
Observational-Tx |
1,201 patients and 625 spouses or partners |
To identify determinants of health-related quality of life after primary treatment of prostate cancer and to measure the effects of such determinants on satisfaction with the outcome of treatment in patients and their spouses or partners. |
Adjuvant hormone therapy was associated with worse outcomes across multiple quality-of-life domains among patients receiving brachytherapy or radiotherapy. Patients in the brachytherapy group reported having long-lasting urinary irritation, bowel and sexual symptoms, and transient problems with vitality or hormonal function. Adverse effects of prostatectomy on sexual function were mitigated by nerve-sparing procedures. After prostatectomy, urinary incontinence was observed, but urinary irritation and obstruction improved, particularly in patients with large prostates. No treatment-related deaths occurred; serious adverse events were rare. Treatment-related symptoms were exacerbated by obesity, a large prostate size, a high prostate-specific antigen score, and older age. Black patients reported lower satisfaction with the degree of overall treatment outcomes. Changes in quality of life were significantly associated with the degree of outcome satisfaction among patients and their spouses or partners. |
1 |
73. Ferrer M, Guedea F, Suarez JF, et al. Quality of life impact of treatments for localized prostate cancer: cohort study with a 5 year follow-up. Radiother Oncol. 2013;108(2):306-313. |
Observational-Tx |
704 participants |
To assess long-term quality of life (QoL) impact of treatments in localized prostate cancer patients treated with radical prostatectomy, external beam radiotherapy or brachytherapy. |
Brachytherapy's QoL impact was restricted to the urinary domain, Generalized Estimating Equation models showed score changes at five years of -12.0 (95% CI=-15.0, -9.0) in incontinence and -5.3 (95% CI=-7.5, -3.1) in irritative-obstructive scales. Compared to brachytherapy, radical prostatectomy fared +3.3 (95% CI=+0.0, +6.5) points better in irritative-obstructive but -17.1 (95% CI=-22.7, -11.5) worse in incontinence. Sexual deterioration was observed in radical prostatectomy (-19.1; 95% CI=-25.1, -13.1) and external radiotherapy groups (-7.5; 95% CI=-12.5, -2.5). |
1 |
74. Gay HA, Michalski JM, Hamstra DA, et al. Neoadjuvant androgen deprivation therapy leads to immediate impairment of vitality/hormonal and sexual quality of life: results of a multicenter prospective study. Urology. 2013;82(6):1363-1368. |
Experimental-Tx |
450 patients |
To evaluate the immediate effects of neoadjuvant androgen deprivation therapy (NADT) on health-related quality of life (HRQOL) among patients undergoing radiation therapy (RT) for newly diagnosed prostate cancer. |
From among 450 patients who completed the Expanded Prostate Cancer Index Composite-26 before and 2 months after NADT start, 71 received NADT before proceeding with definitive RT. Patients receiving NADT experienced significant impairment in vitality/hormonal (P <.0001) and sexual (P <.0001) HRQOL after NADT initiation. The mean +/- standard deviation vitality/hormonal score fell from an average of 94.1 +/- 9.7 before NADT to 78.7 +/- 16.3 two months after NADT initiation; and sexual HRQOL fell from a mean of 51.7 +/- 31.1 pretreatment to 32.3 +/- 26.1 after NADT initiation. Both these HRQOL domain changes exceeded the thresholds for clinical significance. Patients receiving NADT also experienced a significant impairment in urinary continence (P = .024), although this difference did not meet the criteria for clinical significance. |
1 |
75. Hamstra DA, Conlon AS, Daignault S, et al. Multi-institutional prospective evaluation of bowel quality of life after prostate external beam radiation therapy identifies patient and treatment factors associated with patient-reported outcomes: the PROSTQA experience. Int J Radiat Oncol Biol Phys. 2013;86(3):546-553. |
Observational-Tx |
292 men |
To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). |
Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/big problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum >/=25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P=.015) and predicted increased risks for moderate to big fecal incontinence (P=.0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 >/=25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P=.03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P=.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P=.026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P=.03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P=.018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. |
1 |
76. Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med. 2013;368(5):436-445. |
Observational-Tx |
3,533 men |
To compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy. |
Patients undergoing prostatectomy were more likely to have urinary incontinence than were those undergoing radiotherapy at 2 years (odds ratio, 6.22; 95% confidence interval [CI], 1.92 to 20.29) and 5 years (odds ratio, 5.10; 95% CI, 2.29 to 11.36). However, no significant between-group difference in the odds of urinary incontinence was noted at 15 years. Similarly, although patients undergoing prostatectomy were more likely to have erectile dysfunction at 2 years (odds ratio, 3.46; 95% CI, 1.93 to 6.17) and 5 years (odds ratio, 1.96; 95% CI, 1.05 to 3.63), no significant between-group difference was noted at 15 years. Patients undergoing prostatectomy were less likely to have bowel urgency at 2 years (odds ratio, 0.39; 95% CI, 0.22 to 0.68) and 5 years (odds ratio, 0.47; 95% CI, 0.26 to 0.84), again with no significant between-group difference in the odds of bowel urgency at 15 years. |
2 |
77. Nguyen PL, Je Y, Schutz FA, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. Jama 2011; 306(21):2359-2366. |
Meta-analysis |
4,141 patients |
To perform a systematic review and meta-analysis of randomized trials to determine whether ADT is associated with cardiovascular mortality, prostate cancer-specific mortality (PCSM), and all-cause mortality in men with unfavorable-risk, nonmetastatic prostate cancer. |
Among 4141 patients from 8 randomized trials, cardiovascular death in patients receiving ADT vs control was not significantly different (255/2200 vs 252/1941 events; incidence, 11.0%; 95% CI, 8.3%-14.5%; vs 11.2%; 95% CI, 8.3%-15.0%; RR, 0.93; 95% CI, 0.79-1.10; P = .41). ADT was not associated with excess cardiovascular death in trials of at least 3 years (long duration) of ADT (11.5%; 95% CI, 8.1%-16.0%; vs 11.5%; 95% CI, 7.5%-17.3%; RR, 0.91; 95% CI, 0.75-1.10; P = .34) or in trials of 6 months or less (short duration) of ADT (10.5%; 95% CI, 6.3%-17.0%; vs 10.3%; 95% CI, 8.2%-13.0%; RR, 1.00; 95% CI, 0.73-1.37; P = .99). Among 4805 patients from 11 trials with overall death data, ADT was associated with lower PCSM (443/2527 vs 552/2278 events; 13.5%; 95% CI, 8.8%-20.3%; vs 22.1%; 95% CI, 15.1%-31.1%; RR, 0.69; 95% CI, 0.56-0.84; P < .001) and lower all-cause mortality (1140/2527 vs 1213/2278 events; 37.7%; 95% CI, 27.3%-49.4%; vs 44.4%; 95% CI, 32.5%-57.0%; RR, 0.86; 95% CI, 0.80-0.93; P < .001). |
M |
78. Levine GN, D'Amico AV, Berger P, et al. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation. 2010;121(6):833-840. |
Review/Other-Tx |
N/A |
Advisory to review and summarize the metabolic effects of ADT, to evaluate the data regarding a possible relationship between ADT and cardiovascular events in patients with prostate cancer, and to generate suggestions regarding the evaluation and management of patients, both with and without known cardiac disease, in whom ADT is being initiated. |
There is substantial amount of data demonstrating that ADT adversely affects traditional cardiovascular risk factors, including serum lipoproteins, insulin sensitivity, and obesity. Given the metabolic effects of ADT, it is advisable that patients in whom ADT is initiated be referred to their primary care physician for periodic follow-up evaluation. |
4 |
79. Saylor PJ, Smith MR. Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol. 2013;189(1 Suppl):S34-42; discussion S43-34. |
Review/Other-Tx |
N/A |
A review focused on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease. |
Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol. |
4 |