Risk of Secondary Pelvic Cancers Following Radiotherapy for Prostate Cancer

Area of Science:

• Oncology
• Radiation Oncology
• Epidemiology

Background:

• The risk of secondary pelvic cancer (SC) following radiotherapy (RT) for prostate cancer (PC) requires updated evaluation.
• Existing data synthesis is limited by potential detection bias from RT-related bleeding.

Purpose of the Study:

• To synthesize observational studies and randomized trials to clarify the association between RT for PC and SC risk.
• To evaluate the primary outcome of relative risk (RR) of death, accounting for potential detection bias.

Main Methods:

• Systematic review and meta-analysis of studies published between 2001-2025.
• Inclusion of systematic reviews, meta-analyses, and randomized trials comparing RT for PC with radical prostatectomy (RP) or mixed cohorts.
• Primary outcome: relative risk (RR) of death, with secondary analysis of SC incidence.

Main Results:

• In randomized trials with >10 years follow-up, SC occurred in 25.3% of RT patients vs. 20.8% in RP/hormone therapy groups.
• Deaths from other cancers were 8.5% (RT) vs. 7.2% (RP/hormone therapy).
• Median converted RR of death from SC was 1.05; absolute excess incidence of SC was 4.5% over >10 years.

Conclusions:

• Radiotherapy for prostate cancer is associated with a small but consistent increase in secondary pelvic cancer risk.
• The excess risk observed in randomized trials is smaller than in retrospective studies, suggesting confounding factors like lifestyle and comorbidities may play a role.
• The findings suggest that much of the apparent risk in prior reports may reflect confounding and/or detection bias rather than a direct radiation effect.