The therapeutic efficacy of radical prostatectomy and external beam radiation therapy in patients with histologic variants of prostate cancer.

366 Background: To evaluate the prognostic value of histologic variants of prostate cancer (PCa) in men treated with radical prostatectomy (RP) and external beam radiation therapy (EBRT). Methods: We identified patients with localized PCa treated with EBRT (n=221) or RP (n=2,039) at West China Hospital between 2011 and 2023. 1:3 propensity score matching was performed to adjust the patients’ backgrounds. Histologic variants of PCa included intraductal carcinoma of the prostate (IDCP), ductal adenocarcinoma of the prostate (DA), and neuroendocrine differentiation (NED), all biopsy-confirmed. We compared the biochemical recurrence (BCR)-free survival using the Phoenix definition (prostate-specific antigen PSA nadir plus 2 ng/mL) for EBRT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free survival using the same PSA cut-off value of 0.2 ng/mL for both EBRT and RP. Results: Totally, 884 patients were included. Patients with histologic variants of PCa harbored the worst prognosis compared with adenocarcinoma of the prostate (PAC) in both RP and EBRT cohort (RP: 23-Mo vs 138-Mo, p < 0.001; EBRT: neither reached the median BCR-free survival, p < 0.001). Subsequent multivariate cox regression analysis further established histologic variants of PCa as an independent risk factor in RP and EBRT cohort (RP: HR: 2.00, 95%CI: 1.55-2.60, p < 0.001; EBRT: HR: 2.19, 95%CI: 1.03-4.66, p = 0.042;). Comparing the BCR-free survival using the above definitions for RP and EBRT showed that EBRT yielded a significantly better BCR-free survival than did RP whether in PAC or histologic variants of PCa (PAC: RP vs EBRT: 138-Mo vs not reached, p < 0.001; Histologic variants of PCa: RP vs EBRT: 23.3-Mo vs not reached, p < 0.001;). When the surgical definition was applied to both treatments, there was no significant difference between EBRT and RP in PAC (138 months vs not reached, p=0.062), whereas EBRT remained superior in histologic variants of PCa (23.3 months vs not reached, p=0.001). Conclusions: Histologic variants of PCa is associated with inferior prognosis after both RP and EBRT. EBRT was linked to longer BCR-free survival than RP, including under a uniform surgical definition, among patients with histologic variants of PCa. EBRT should be strongly considered when selecting definitive therapy for localized histologic variants of PCa.