The impact of positive surgical margins after cystectomy on oncological outcomes: a nationwide study

Abstract

Objective: To evaluate whether surgical margin status, alongside existing postoperative risk indicators, improves the identification of bladder cancer patients who may benefit from adjuvant therapy following radical cystectomy (RC).

Methods: In this nationwide cohort study, patients aged ≥18 years diagnosed with muscle-invasive bladder cancer (MIBC) without nodal or distant metastasis (cT2-4aN0/xM0) between November 2017 and December 2020 who underwent RC were selected from the Netherlands Cancer Registry. Detailed information on surgical margin status was obtained through linkage with the Dutch central pathology database, Palga. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to assess the independent prognostic effect of positive surgical margins (carcinoma in situ (CIS) only or invasive carcinoma) on PFS and OS.

Results: We identified 1445 MIBC patients treated by RC (53% open, 47% robot-assisted), of whom 135 (9.3%) had positive surgical margins (10.7% in the open and 7.7% in the robot-assisted cohort). In the entire cohort, OS was 79% and 60% at 12 and 48 months after RC, respectively. PFS was 70% and 61% at 12 and 24 months, respectively. Multivariable Cox regression showed worse PFS (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.67-2.72) and OS (HR 2.02, 95% CI 1.58-2.58) in patients with surgical margins with invasive carcinoma vs patients with negative margins. Patients with only CIS in the margins also appeared to have worse PFS (HR 1.60, 95% CI 1.00-2.58) but these results were not statistically significant. No difference was found for OS (HR 1.30, 95% CI 0.80-2.12).

Conclusion: Positive margins should be considered a 'high risk feature', as they result in increased risk of disease progression and impaired survival outcomes. These findings support further investigation of the potential efficacy of adjuvant therapy (i.e., radiotherapy and systemic therapy) among patients with positive surgical margins.

Keywords: adjuvant therapy; muscle‐invasive bladder cancer; overall survival; radical cystectomy; surgical margins.

Fig. 1

Flowchart of cohort selection. Neoadjuvant radiotherapy for the following reasons: previous chemotherapy for another malignancy, histological variant, treatment of haematuria while cystectomy postponed due to COVID‐19 limitations. NMIBC, non‐muscle‐invasive bladder cancer.

Fig. 2

Observed progression‐free and overall survival of patients stratified by pathological TNM and surgical margin status after radical cystectomy. (A) Observed 24‐month progression‐free survival and (B) 48‐month overall survival stratified by surgical margin status. (C) Observed 24‐month progression‐free survival and (D) 48‐month overall survival stratified by (y)pTN‐stage* and surgical margin status. Four patients had the combination of (y)pTN low risk and positive invasive margins and were omitted from parts C and D because of small group size. *(y)pTN high‐risk: pT3‐4 and/or pN+ without neoadjuvant chemotherapy (NAC) or ypT2‐4 and/or ypN+ following NAC; (y)pTN low‐risk: all other stages. CIS, carcinoma in situ.