Ernandez John, Kaul Sumedh, Fleishman Aaron, Korets Ruslan, Chang Peter, Wagner Andrew, Kim Simon, Bellmunt Joaquim, Kaplan Irving, Olumi Aria F, Gershman Boris
Harvard Medical School, Boston, MA, USA.
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Bladder Cancer. 2022 Dec 14;8(4):405-417. doi: 10.3233/BLC-220031. eCollection 2022.
Survival with locally advanced bladder cancer (LABC) following radical cystectomy (RC) remains poor. Although adjuvant chemotherapy (AC) is standard of care, one small, randomized trial has suggested a potential survival benefit when combined with post-operative radiotherapy (PORT).
We examined the association of AC + PORT with overall survival (OS) in patients with LABC after RC.
Using a prior phase 2 trial to inform design, we conducted observational analyses to emulate a hypothetical target trial of patients aged 18-79 years with pT3-4 Nany M0 or pTany N1-3 M0 urothelial bladder carcinoma following RC who were treated with AC (multiagent chemotherapy within 3 months of RC) with or without PORT (≥45 Gy to the pelvis) from 2006-2015 in the NCDB. Patients who received preoperative chemotherapy or radiotherapy were excluded. The associations of treatment with OS were evaluated using multivariable Cox regression.
1,684 patients were included, with 66 receiving AC + PORT and 1,618 AC alone. Compared to patients treated with AC alone, those treated with AC + PORT were more likely to have pT4 disease (52% vs 26%; < 0.01), positive surgical margins (44% vs 17%; < 0.01), and be treated at a non-academic facility (75% vs 53%; < 0.01). Crude 5-year OS was 19% for AC + PORT versus 36% for AC alone ( = 0.01). Adjusted 5-year OS was 33% for AC + PORT versus 36% for AC alone ( = 0.49). After adjusting for baseline characteristics including pathologic features, AC + PORT was not associated with improved OS compared to AC alone (HR 1.11; 95% CI 0.82-1.51).
Although infrequently utilized, the addition of radiotherapy to AC is not associated with improved OS in LABC. These results highlight the need for prospective trials to better define the potential benefits from PORT with regard to symptomatic progression and oncologic outcomes.
根治性膀胱切除术后局部晚期膀胱癌（LABC）患者的生存率仍然很低。尽管辅助化疗（AC）是标准治疗方案，但一项小型随机试验表明，术后放疗（PORT）联合AC可能具有生存获益。
我们研究了LABC患者根治性膀胱切除术后AC + PORT与总生存期（OS）的相关性。
利用之前的一项2期试验指导设计，我们进行了观察性分析，以模拟一项假设的目标试验，该试验纳入了2006年至2015年在国家癌症数据库（NCDB）中接受AC（根治性膀胱切除术后3个月内进行多药化疗）联合或不联合PORT（盆腔放疗剂量≥45 Gy）治疗的18至79岁的pT3-4 Nany M0或pTany N1-3 M0尿路上皮膀胱癌患者。排除接受术前化疗或放疗的患者。使用多变量Cox回归评估治疗与OS的相关性。
共纳入1684例患者，其中66例接受AC + PORT治疗，1618例仅接受AC治疗。与仅接受AC治疗的患者相比，接受AC + PORT治疗的患者更有可能患有pT4疾病（52%对26%；P < 0.01）、手术切缘阳性（44%对17%；P < 0.01），并且在非学术机构接受治疗（75%对53%；P < 0.01）。AC + PORT组的5年粗生存率为19%，而AC单独治疗组为36%（P = 0.01）。AC + PORT组的调整后5年生存率为33%，AC单独治疗组为36%（P = 0.49）。在调整包括病理特征在内的基线特征后，与单独使用AC相比，AC + PORT与OS改善无关（风险比1.11；95%置信区间0.82 - 1.51）。
尽管AC联合PORT的应用并不常见，但在LABC患者中，AC联合放疗与OS改善无关。这些结果凸显了开展前瞻性试验以更好地明确PORT在症状进展和肿瘤学结局方面潜在获益的必要性。
