When selecting between radical prostatectomy (RP) and curative-intent radiotherapy (RT) for non-metastatic prostate cancer, long-term treatment-related morbidity is a crucial consideration. Yet, population-level data comparing organ-specific side effects over extended follow-up remain limited. We examine the incidence, distribution, and 18-year risk difference of bladder, urethral, and rectal-specific side effects following curative-intent treatment for prostate cancer.
All men residing in Stockholm who underwent curative-intent therapy for non-metastatic prostate cancer between July 2005 and December 2023 were identified from the Stockholm Prostate Cancer Diagnostics Register (STHLM0) and its linked registers. Follow-up continued until the occurrence of organ-specific side effect, salvage therapy, death, or study end. Organ-specific side effect was defined using ICD-10 codes capturing bladder-neck obstruction, irradiation cystitis, urethral strictures, fecal incontinence, rectal stenosis, radiation proctitis, and related other conditions, complemented by procedure codes reflecting clinical management. Only hospital admissions or specialist care records were included, to allow comparison of severe cases. Flexible parametric survival models estimated the cumulative incidence and absolute risk difference (aRD), accounting for death as a competing event. Comprehensive adjustments were made for demographic, socioeconomic, clinical, and tumor characteristics, as well as prior healthcare utilization and comorbidity burden.
Among 17,794 men treated with curative intent, 6,462 (63.7%) received radiotherapy and 11,332 (36.3%) underwent prostatectomy. During 18 years follow-up, 3,390 men (19.3%) experienced any severe organ-specific side effects requiring hospitalization or specialist management (RP 1,636; 15%, RT 1,1754; 27%). Colorectal injury was most frequent (1,862; 10.6%, RP 633; 6%, RT 1,229; 19%), followed by bladder (1,529; 8.7%, RP 905; 8%, RT 624; 10%) and urethral damage (544; 3.1%, RP 305; 3%, RT 239; 4%). After 18 years, the aRD for any organ-specific side effect was 8.9% (95% CI 5.6%–12.1%), favoring RP, while bladder-specific harm was lower in men treated with RT with aRD 3.1% (95% CI 0.5%–5.8%). A small short-term excess risk after RP (aRD 1.0%; 95% CI 0.5%–1.4%) was seen for urethral damage at 2-years, but at 18-years, it was higher among men treated with RT aRD 2.5% (95% CI 0.4%–4.6%). Colorectal-specific side effects were more frequent among men treated with RT, with an 18-year aRD of 20.3% (95% CI 17.3%–23.3%). Severe radiation proctitis accounted for the largest share of these cases in RT (n=838).
Severe organ-specific side effects following curative-intent therapy for prostate cancer is considerable. However, RT carries a higher long-term risk—mainly from colorectal complications such as radiation proctitis warranting specialist care or admission, and urethral damage at the long-term. RP is associated with a slightly higher short-term risk of urethral damage, and bladder-specific side effects risk at long follow-up. While the type and mechanism of organ-specific side effects differ substantially between radical treatment modalities, the findings underscore the importance of considering late toxicity profiles when counseling men on curative treatment options.
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