A total of 1,700 patients were included in the study, among whom 805 underwent RC without any perioperative chemotherapy (NC), 761 received chemotherapy followed by RC (RC), and 134 underwent RC followed by chemotherapy (AC). Among RC patients, 98 also received adjuvant chemotherapy. Presurgical chemotherapy regimens included gemcitabine/cisplatin (58.1%), MVAC/dose-dense MVAC (16.6%), and gemcitabine/carboplatin (8.8%). In the adjuvant setting, 41.8% of patients received gemcitabine/cisplatin, 25.4% received gemcitabine/carboplatin, and 19.4% received other regimens. The median follow-up was 24.2 months, after which 472 patients exhibited disease recurrence after RC, 135 underwent salvage treatment, and 797 patients died. Most patients had cT2 tumors at diagnosis (55.1%). Pathologic complete response (pCR) occurred in 15.2% of all patients. The median number of dissected lymph nodes was 18, and nodal metastasis was present in 23.3% of patients. The 5-year recurrence-free survival (RFS) rate was 38.6% for NC, 34.3% for PC, and 31.2% for AC. The 5-year overall survival (OS) rate was 44.9% for NC, 44.6% for PC, and 35.4% for AC.
To identify the specific effects of presurgical chemotherapy, the investigators compared survival in patients in the PC versus NC groups. A higher proportion of patients in the PC group achieved pathologic downstaging (41.1% vs. 28.5%) and pCR (22.1% vs. 8.9%) than those in the NC group (p < 0.00001). Median OS was significantly higher in the RC group (49.9 months) than in the NC group (35.3 months, p = 0.018). When stratified by clinical T-stage, only cT2 patients exhibited benefits in RFS and OS from presurgical chemotherapy. Next, the investigators characterized the clinical benefit from adjuvant chemotherapy by comparing outcomes among AC versus NC patients. AC was associated with RFS and OS benefits (p < 0.0001), particularly among patients with pT3, pT4, or pN+ disease.
This study sheds light on how practice patterns based on clinical trials perform in the ‘real world” setting. While the study showed that pathologic response rates to neoadjuvant chemotherapy were modest, the relationship between complete pathologic response and micro-metastatic disease needs to be understood better. The findings from this study highlight the potential value of a personalized approach to neoadjuvant and adjuvant chemotherapy. Emerging biomarkers, including circulating tumor DNA, have potential value in this space.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References
- Li R, Naidu S, Fan W, et al. Effectiveness of perioperative chemotherapy and radical cystectomy in treating bladder cancer [published online ahead of print, 2023 Oct 23]. Urol Oncol. 2023;S1078-1439(23)00332-0. doi:10.1016/j.urolonc.2023.09.017
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