Table 1. Characteristics of included studies (N = 18).
| Study ID | study design | Sites/Time | Population/Median age(RP vs. RT or Alone vs. combination) | Median follow-up | Comparison of treatment/N | End-points | Definition of high-risk PCa |
|---|---|---|---|---|---|---|---|
| Studies without combined regimens (N = 6) | |||||||
| Zelefsky et al. 2010 [16] | R. cohort | New York, US 1993-2002 | Clinical stages T1c-T3b/60(55–65) vs. 69(64–73) | RP: 5 yr EBRT: 5.1 yr | RP vs. EBRT 1318 vs. 1062 | CSM, DMFS | T3, Gleason 8–10, or PSA>20ng/ml |
| Merino et al. 2013 [17] | R. cohort | Chile 1990–2010 | Localized PCa/63 (62.6–63.5) vs. 70(69–71) | RP: 91.7 mo IMRT: 76 mo | RP vs. IMRT 993 vs. 207 | OS, CSS, BDFS | D'Amico definition |
| Tewari et al. 2007 [18] | R. cohort | New York, US 1980–1997 | High-risk localized PCa 62.9 ± 6.2 vs. 68.1 ± 5.8 | RP vs. EBRT vs. WW 68 vs. 53 vs. 52 mo | RP vs. EBRT vs. WW 119 vs. 137 vs. 197 | OS,CSS | Poorly differentiated, Gleason 8–10 |
| Kibel et al. 2012 [19] | P. and R. cohort | Missouri/Ohio, US 1995–2005 | Localized PCa 60(56–65) vs. 69(63–73) | 67 mo | RP vs. EBRT vs. BT 6485vs. 2264 vs.1680 | OS, CSM | D'Amico definition |
| Stokes et al. 2000 [20] | R. cohort | Alabama, US 1988–2000 | Localized PCa 66(43–79) vs. 72(49–87) | RP vs. EBRT vs. SI 66 vs. 72 vs.74 mo | RP vs. EBRT vs. SI 222 vs. 132 vs. 186 | BDFS | T2c, T3, Gleason 7–10, or PSA>20 ng/ml |
| Cooperberg et al. 2010 [21] | P. and R. cohort | 40 community-based centers, US 1995–2008 | Localized PCa 62(56–67) vs. 72(67–75) | NA | RP vs. EBRT vs. ADT 5066 vs. 1143 vs. 1329 | CSM, ACM | CAPRA Score 6~10 |
| Studies with combined regimens(N = 12) | |||||||
| Siddiqui et al. 2011 [22] | Case-controlled study | Rochester, US 1987–2010 | Localized T3b PCa/66(48–78) vs. 65(48–79) | 10 yr | RP vs. RP+aADT 191 vs.191 | OS, CSS | No |
| Bastide et al. 2011 [23] | R. cohort | Aixen, France 1994–2008 | Localized T3b PCa/65.3 vs. 63.7 | 60.3 mo | RP vs. RP+aADT 82 vs. 41 | BCR | No |
| Koie et al. 2014 [24] | R. cohort | Hirosaki, Japan 2004–2012 | High-risk localized PCa/71 vs. 73.5 | RP+nADTvs.RT+nADT 37.6 vs.31.5 mo | RP+nADT vs. RT+nADT 216 vs. 81 | OS, BRFS | T2c/T3, Gleason 8–10,PSA>20 ng/ml |
| Lee et al. 2014 [25] | R. cohort | Seoul, Korea 1990–2009 | High-risk localized PCa/67.5 ± 7.0 vs. 68.6 ± 8.4 | 76 mo | RP vs. EBRT+(n+a)ADT 251 vs. 125 | CSM | NCCN definition |
| Hsu et al. 2006 [26] | R. cohort | Leuven, Belgium 1987–2004 | Unilateral cT3 PCa/63.3(41–79) vs.65.1(51–75) | 74.7 mo | RP vs. RT+nADT 200 vs. 35 | OS, CSS | No |
| Westover et al. 2012 [27] | R. cohort | Boston/Durham, US 1988–2009 | Localized PCa, and Gleason 8–10/65(58–69) vs.70(66–73) | 4.62 yr | RP vs. RT+BT+(n+c)ADT 285 vs. 372 | CSM | D'Amico definition |
| Bolla et al. 1997 [12] | RCT | France, Netherlands, Switzerland1987–1995 | High-grade localized and locally advanced PCa/70(51–80) vs. 71(54–80) | 45 mo | RT vs. RT+(c+a)ADT 198 vs. 203 | OS | No |
| D'Amico et al. 2004 [13] | RCT | Harvard outreach, US 1995–2001 | Intermediate and high-risk localized PCa/73(51–81) vs. 72(49–82) | 4.52 yr | CRT vs. CRT+(c+a)ADT 104 vs. 102 | Time to PSA failure, OS | Gleason 7–10, PSA>20 ng/ml |
| Pilepich et al. 1997 [14] | RCT | Scranton/Wisconsin,US, 1987–1992 | PCa with cT3 or regional node involved/ | 4.5 yr | RT vs. RT+aADT 468 vs. 477 | CSS | Gleason 8–10 |
| Pilepich et al. 2001 [15] | RCT | California/Sacramento, US, 1987–1991 | Bulky PCa (T2–T4) with/without pelvic node involvement/ | 6.7 yr | RT vs. RT+(n+c)ADT 230 vs. 226 | OS, CSM | Gleason 8–10 |
| Galalae et al. 2004 [28] | P. cohort | Germany; US 1986–2000 | Localized PCa/ | 5 yr | HDR-BT+ EBRT vs. HDR-BT +EBRT + (n+c)ADT: 434 vs. 177 | OS,CSS | NCCN definition |
| Demanes et al. 2009 [29] | P. cohort | Oakland, CA1991–2008 | Localized PCa/ | 6.4 yr | BT+EBRT vs. BT+EBRT+nADT 211 vs. 200 | OS, BC | NCCN definition |
P. and R. Cohort: prospective and retrospective cohort study. RCT: randomized controlled trial. EBRT: external beam radiotherapy. CRT: 3-dimensional conformal radiation therapy. ADT: androgen-deprivation therapy. nADT: neoadjuvant ADT. (n+a)ADT: neoadjuvant and adjuvant ADT. (n+c)ADT: neoadjuvant and concurrent ADT. IMRT: intensity-modulated radiation therapy. BT: brachytherapy. HDR-BT: High Dose Rate BT represented one form of BT. SI: Seed implantation represented the other form of BT. WW: watchful waiting. OS: Overall Survival. CSS: Cancer-Specific Survival. CSM: Cancer-Specific Mortality. ACM: All-Cause Mortality (To assess perioperative mortality and death from complicationsof radiation). DMFS: Distant Metastases-Free Survival. BDFS: Biochemical Disease-Free Survival. BRFS: biochemical recurrence-free survival. BC: Biochemical control of PSA testing. BCR: Biochemical recurrence of PSA testing. D'Amico definition: PSA >20ng/ml, Gleason score 8–10, or clinical stage ≥ T2c. NCCN definition: PSA >20ng/ml, Gleason score 8–10, or clinical stage ≥T3a. CAPRA Score: Ranging from 0–10, mainly based on PSA levels, biopsy Gleason grade, clinical T stage, age at diagnosis and percentage of positive biopsy cores; a score of 6–10 points was considered to be high-risk. Dates were not available. NA: not applicable.