Defining Clinically Meaningful Positive Surgical Margins in Patients Undergoing Radical Prostatectomy for Localised Prostate Cancer

The impact of positive surgical margins (PSMs) on the risk of metastases in prostate cancer (PCa) patients treated with radical prostatectomy (RP) is still debated. To identify PSM features associated with recurrence in a stage-by-stage analysis. A total of 1757 PCa patients treated with RP without neoadjuvant or adjuvant treatments between 2011 and 2017 were identified. Patients were stratified according to the presence of PSM and to margins characteristics in three groups: no versus favourable (single margin <3 mm) versus unfavourable (≥3 mm or multifocal margin) PSMs. Predictors of biochemical recurrence (BCR) and clinical recurrence (CR) were assessed using semiparametric Cox proportional hazard models. Overall, 285 (16%) patients had PSMs; 146 (51%) had a unifocal PSM, while 139 (49%) had a multifocal PSM. The median length of a PSM was 1 mm. Overall, 120 (42%) versus 165 (58%) patients had favourable versus unfavourable PSMs. In patients with ≤pT3a and pathologic grade group ≤3 disease (n = 1351), favourable (hazard ratio [HR]: 2.24; 95% confidence interval [CI]: 1.19–4.22) and unfavourable (HR: 2.68; 95% CI: 1.49–4.84) PSMs significantly increased the risk of BCR (p < 0.01). However, they were not associated with CR (all p > 0.05). Conversely, in patients with pT3b/4 and/or pathologic grade group 4–5 and/or pN1 (n = 406), only an unfavourable PSM was associated with both BCR (HR: 2.96; 95% CI: 1.19–4.22) and CR (HR: 2.60; 95% CI: 1.07–6.30; all p ≤ 0.04). Although the presence of PSMs was associated with an increased risk of BCR in all stages, only men with adverse pathologic characteristics and an unfavourable PSM were at an increased risk of experiencing metastases as compared with their counterparts with no or a single margin shorter than 3 mm. In this study, we defined a new category of unfavourable positive surgical margins (namely, ≥3 mm and/or multifocal), which confers a higher risk of developing metastasis in men with more aggressive pathologic features.