Impact of positive surgical margins on biochemical recurrence and metastases after radical prostatectomy: 5-year follow-up of a nationwide real-world cohort

Background While overall survival following radical prostatectomy (RP) for localised prostate cancer (PCa) is generally good, biochemical recurrence (BCR) and development of metastases remain challenges, often requiring salvage or palliative therapies. This study examines the impact of the presence, extent, and location of positive surgical margins (PSMs) on the risk of BCR and metastases in a nationwide cohort of PCa patients with five-years of follow-up. Methods All patients diagnosed with PCa in the Netherlands between October 2015 and April 2016 who underwent a RP were included in a prospective cohort. Data of these patients from the Netherlands Cancer Registry and PALGA pathology registry were analysed. BCR was defined as PSA ≥0.1 ng/ml >28 days post-RP. Exclusion criteria were (neo)adjuvant treatment, pN1 disease, and salvage therapy initiated at PSA <0.1 µg/l. Multivariable Cox regression analyses evaluated the impact of PSM presence, extent, and location on the risk of BCR and metastases. Results Of 998 patients, 311 (31%) had PSMs (median length 5.0 mm). Over 5 years of follow-up, 36% of patients experienced BCR and 11% developed metastases. PSMs ≥3 mm were associated with a significantly increased risk of BCR (HR 2.04, 95% CI 1.58-2.64, p<0.001) and metastases (HR 2.12, 95% CI 1.21-3.74, p=0.009) compared to negative surgical margins (NSMs). In contrast, PSMs <3 mm or PSM location did not significantly increase the risk of BCR or metastases. Conclusions PSMs ≥3 mm appear to be independently associated with an increased risk of BCR and metastases following RP. Therefore, avoiding or limiting the extent of PSMs during RP remains essential.