Bosveld Jikke, Nguyen Tri Q, Boormans Joost L, Witjes J Alfred, van der Heijden Antoine G, Mehra Niven, Kiemeney Lambertus A, Aben Katja K H, Meijer Richard P, Richters Anke
Department of Oncological Urology, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Research, The Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands.
BJU Int. 2025 May;135(5):766-774. doi: 10.1111/bju.16611. Epub 2024 Dec 4.
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).
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.
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).
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.
评估手术切缘状态与现有的术后风险指标一起，是否能更好地识别出在根治性膀胱切除术（RC）后可能从辅助治疗中获益的膀胱癌患者。
在这项全国性队列研究中，从荷兰癌症登记处选取了2017年11月至2020年12月期间年龄≥18岁、诊断为肌层浸润性膀胱癌（MIBC）且无淋巴结或远处转移（cT2-4aN0/xM0）并接受了RC的患者。通过与荷兰中央病理学数据库Palga建立联系，获取了关于手术切缘状态的详细信息。采用Kaplan-Meier方法评估总生存期（OS）和无进展生存期（PFS）。进行多变量Cox回归分析，以评估手术切缘阳性（仅原位癌（CIS）或浸润性癌）对PFS和OS的独立预后影响。
我们确定了1445例接受RC治疗的MIBC患者（53%为开放手术，47%为机器人辅助手术），其中135例（9.3%）手术切缘阳性（开放手术组为10.7%，机器人辅助手术组为7.7%）。在整个队列中，RC术后12个月和48个月时的OS分别为79%和60%。PFS在12个月和24个月时分别为70%和61%。多变量Cox回归显示，与切缘阴性的患者相比，手术切缘有浸润性癌的患者PFS更差（风险比（HR）2.13，95%置信区间（CI）1.67-2.72），OS也更差（HR 2.02，95%CI 1.58-2.58）。切缘仅为CIS的患者PFS似乎也较差（HR 1.60，95%CI 1.00-2.58），但这些结果无统计学意义。OS方面未发现差异（HR 1.30，95%CI 0.80-2.12）。
切缘阳性应被视为一种“高风险特征”，因为它们会导致疾病进展风险增加和生存结果受损。这些发现支持进一步研究辅助治疗（即放疗和全身治疗）对手术切缘阳性患者的潜在疗效。
