de Angelis Mario, Siech Carolin, Di Bello Francesco, Rodriguez Peñaranda Natali, Goyal Jordan A, Tian Zhe, Longo Nicola, Chun Felix K H, Puliatti Stefano, Saad Fred, Shariat Shahrokh F, Gandaglia Giorgio, Moschini Marco, Stabile Armando, Montorsi Francesco, Briganti Alberto, Karakiewicz Pierre I
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Frankfurt, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
Eur Urol Focus. 2024 Oct 3. doi: 10.1016/j.euf.2024.09.013.
Trimodal therapy (TMT) provided significant survival advantage relative to external beam radiation therapy (EBRT) alone in prospective trials. However, the magnitude of survival benefit has not been validated in population-based studies. The objective of this study is to determine whether TMT is associated with lower cancer-specific mortality (CSM) rates relative to EBRT.
Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4aN0M0 urothelial carcinoma of urinary bladder (UCUB) treated with either TMT or EBRT. Cumulative incidence plots and multivariable competing risk regression (CRR) models addressed CSM after additional adjustment for other-cause mortality and standard covariates. The same methodology was repeated according to stage and age categories.
Of 4471 patients, 3391 (76%) underwent TMT versus 1080 (24%) EBRT. TMT rates increased over time in the overall cohort (estimated annual percent change [EAPC]: 1.8%, p < 0.001) as well as in organ-confined (OC) stage (EAPC: 1.7%, p < 0.001), but not in non-organ-confined (NOC) stage (p = 0.051). In the overall cohort, 5-yr CSM rates were 43.6% in TMT versus 52.7% in EBRT. In multivariable CRR models, TMT was an independent predictor of lower CSM (hazard ratio [HR]: 0.76, p < 0.001). In OC patients, 5-yr CSM rates were 42.0% in TMT versus 51.9% in EBRT (p < 0.001). In multivariable CRR models, TMT was an independent predictor of lower CSM (HR: 0.74, p < 0.001). Conversely, in NOC patients, TMT did not achieve independent predictor status (p = 0.3).
In this population-based study, relative to EBRT, TMT is associated with lower CSM in OC stage, but not in NOC UCUB patients.
In this report, we investigated the survival benefit of administering systemic chemotherapy in addition to radiotherapy in patients who are candidates for bladder-sparing strategies. We found that the combination of systemic chemotherapy and radiotherapy leads to improved cancer-specific survival compared with radiotherapy alone in patients with organ-confined urothelial carcinoma. We conclude that among patients who are candidates for bladder-sparing strategies, following transurethral resection, the combination of radiotherapy and chemotherapy (namely, trimodal therapy) should always be offered in those with organ-confined urothelial carcinoma.
在前瞻性试验中，三联疗法（TMT）相对于单纯外照射放疗（EBRT）具有显著的生存优势。然而，生存获益的程度尚未在基于人群的研究中得到验证。本研究的目的是确定相对于EBRT，TMT是否与更低的癌症特异性死亡率（CSM）相关。
在监测、流行病学和最终结果数据库（2004 - 2020年）中，我们识别出接受TMT或EBRT治疗的cT2 - T4aN0M0膀胱尿路上皮癌（UCUB）患者。累积发病率图和多变量竞争风险回归（CRR）模型在对其他原因死亡率和标准协变量进行额外调整后分析CSM。根据分期和年龄类别重复相同的方法。
4471例患者中，3391例（76%）接受了TMT，1080例（24%）接受了EBRT。TMT率在整个队列中随时间增加（估计年变化百分比[EAPC]：1.8%，p < 0.001），在器官局限（OC）期也是如此（EAPC：1.7%，p < 0.001），但在非器官局限（NOC）期并非如此（p = 0.051）。在整个队列中，TMT组5年CSM率为43.6%，EBRT组为52.7%。在多变量CRR模型中，TMT是较低CSM的独立预测因素（风险比[HR]：0.76，p < 0.001）。在OC患者中，TMT组5年CSM率为42.0%，EBRT组为51.9%（p < 0.001）。在多变量CRR模型中，TMT是较低CSM的独立预测因素（HR：0.74，p < 0.001）。相反，在NOC患者中，TMT未达到独立预测因素的地位（p = 0.3）。
在这项基于人群的研究中，相对于EBRT，TMT在OC期与较低的CSM相关，但在NOC期UCUB患者中并非如此。
在本报告中，我们研究了对于适合保膀胱策略的患者，在放疗基础上给予全身化疗的生存获益。我们发现，对于器官局限的尿路上皮癌患者，全身化疗与放疗联合可提高癌症特异性生存率，与单纯放疗相比。我们得出结论，在适合保膀胱策略的患者中，经尿道切除术后，对于器官局限的尿路上皮癌患者应始终提供放疗与化疗联合（即三联疗法）。
