Alberto Martini1, Giorgio Gandaglia2, Nicola Fossati3, Simone Scuderi4, Carlo Andrea Bravi4, Elio Mazzone4, Armando Stabile4, Simone Scarcella3, Daniele Robesti4, Francesco Barletta4, Vito Cucchiara5, Vincenzo Mirone5, Francesco Montorsi4, Alberto Briganti4. 1. Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: a.martini.md@gmail.com. 2. Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: gandaglia.giorgio@hsr.it. 3. Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. 4. Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. 5. Department of Urology, Università Federico II, Naples, Italy.
Abstract
BACKGROUND: 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. OBJECTIVE: To identify PSM features associated with recurrence in a stage-by-stage analysis. DESIGN, SETTING, AND PARTICIPANTS: 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 <3mm) versus unfavourable (≥3mm or multifocal margin) PSMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Predictors of biochemical recurrence (BCR) and clinical recurrence (CR) were assessed using semiparametric Cox proportional hazard models. RESULTS AND LIMITATIONS: 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 1mm. 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). CONCLUSIONS: 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 3mm. PATIENT SUMMARY: In this study, we defined a new category of unfavourable positive surgical margins (namely, ≥3mm and/or multifocal), which confers a higher risk of developing metastasis in men with more aggressive pathologic features.
BACKGROUND: 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. OBJECTIVE: To identify PSM features associated with recurrence in a stage-by-stage analysis. DESIGN, SETTING, AND PARTICIPANTS: 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 <3mm) versus unfavourable (≥3mm or multifocal margin) PSMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Predictors of biochemical recurrence (BCR) and clinical recurrence (CR) were assessed using semiparametric Cox proportional hazard models. RESULTS AND LIMITATIONS: 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 1mm. 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). CONCLUSIONS: 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 3mm. PATIENT SUMMARY: In this study, we defined a new category of unfavourable positive surgical margins (namely, ≥3mm and/or multifocal), which confers a higher risk of developing metastasis in men with more aggressive pathologic features.
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