Background
RTOG 9413, 4-arm 2×2 factorial phase III RCT. N=1,292, locally advanced prostate cancer (PSA ≤100 ng/mL, estimated nodal risk ≥15%), enrolled 1995–1999. Randomized to whole pelvis RT (WPRT) vs prostate-only RT (PORT), and neoadjuvant/concurrent ADT vs adjuvant ADT. Horwitz JCO 2008 reports 7-year follow-up.
Interventions and follow up
Arm A: WPRT + neoadjuvant/concurrent ADT
Arm B: WPRT + adjuvant ADT
Arm C: PORT + neoadjuvant/concurrent ADT
Arm D: PORT + adjuvant ADT
Primary endpoint: Progression-free survival (PFS)
mFollow up: Median 7 year
Arm B: WPRT + adjuvant ADT
Arm C: PORT + neoadjuvant/concurrent ADT
Arm D: PORT + adjuvant ADT
Primary endpoint: Progression-free survival (PFS)
mFollow up: Median 7 year
Results
4-year PFS (Roach 2003): WPRT + N/C ADT 54.0% vs best of other arms ~43% (superior; P=.022)
7-year PFS (Horwitz 2008): WPRT+N/C ADT 24.4% vs PORT+N/C ADT 22.6% vs WPRT+adj ADT 14.8% vs PORT+adj ADT 19.6% — NS (interaction P=.065)
7-year OS: No significant differences between arms
7-year PFS (Horwitz 2008): WPRT+N/C ADT 24.4% vs PORT+N/C ADT 22.6% vs WPRT+adj ADT 14.8% vs PORT+adj ADT 19.6% — NS (interaction P=.065)
7-year OS: No significant differences between arms
Adverse events
Acute: WPRT higher acute GI and GU toxicity vs PORT
Late GI grade 3+: Slightly higher with WPRT (~4% vs ~2%), NS
Note: Bowel toxicity the primary concern with whole pelvis RT
Late GI grade 3+: Slightly higher with WPRT (~4% vs ~2%), NS
Note: Bowel toxicity the primary concern with whole pelvis RT
Conclusions
The initial 4-year PFS advantage of WPRT + neoadjuvant/concurrent ADT was not sustained at 7 years (no significant between-arm difference). ADT timing showed a trend favoring neoadjuvant/concurrent. WPRT does not clearly improve outcomes over PORT in unselected patients at 7 years.
Key Limitations
The 4-year advantage attenuated by 7 years, questioning durability. Nodal risk used the Roach formula — now largely replaced by mpMRI/PSMA-PET staging. Mixed risk groups and pre-IMRT techniques.
Clinical Context
Remains controversial; the 4-year WPRT benefit was not maintained at 7 years, limiting guideline incorporation. Retrospective data (incl. SEER) suggest pelvic nodal RT benefit in node-positive/very high-risk patients. Modern practice uses IMRT with elective pelvic nodal irradiation for high nodal risk (>20% Roach or positive PSMA-PET); SPPORT (RTOG 0534) later showed benefit of adding whole pelvic RT with ADT post-prostatectomy.