AUA 2023: Chemotherapy Vs Immunotherapy as Neoadjuvant Therapies in Cisplatin-Eligible Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer

(UroToday.com) The 2023 American Urological Association (AUA) annual meeting held in Chicago, IL between April 28 and May 1st, 2023, was host to a podium session of invasive bladder cancer studies. Dr. Luigi Nocera discussed the results of his group’s study evaluating neoadjuvant chemotherapy versus immunotherapy in cisplatin-eligible patients undergoing a radical cystectomy for muscle invasive bladder cancer.


Neoadjuvant cisplatin-based chemotherapy has long been established as standard of care treatment of cisplatin-eligible patients with muscle invasive bladder cancer (MIBC) undergoing a radical cystectomy, following results of the SWOG-8710 trial by Grossman et al. that demonstrated a 5-year OS benefit of 14% (57% versus 43%, p=0.06).1 More recently, the open-label, single-arm, phase II PURE-01 study of neoadjuvant pembrolizumab demonstrated pT0 rates of 42% in patients with ≤cT3bN0 disease undergoing a RC.2 To date, there are no studies prospectively comparing neoadjuvant chemotherapy and immunotherapy approaches in this setting. As such, the aim of this study was to compare neoadjuvant cisplatin-based chemotherapy and immunotherapy (i.e., pembrolizumab) treatment approaches in MIBC patients undergoing an RC.

This was a retrospective analysis of two prospectively maintained institutional datasets, based at the Moffit Cancer Center and Vita-Salute San Raffaele University in Milan. This study included cisplatin eligible MIBC patients, with patients with cN+ disease or having received adjuvant chemotherapy excluded from the analysis. The study endpoints were recurrence-free survival and the proportion of patients with pT0N0 at final pathology. Survival analysis using Kaplan Meier curves with inverse-probability treatment weighting adjustments and univariable/multivariable logistic regression analyses were employed.

This analysis included 346 patients, of whom 255 (74%) and 91 (26%) received chemotherapy and immunotherapy, respectively. pT0N0 disease was observed in 47% of patients in the immunotherapy group compared to 24% in the chemotherapy group (p<0.001). Unadjusted survival analysis using Kaplan Meier curves demonstrated superior recurrence-free survival outcomes in the immunotherapy group (24-month RFS: 87% versus 77%, p<0.01). This difference was even more pronounced after IPTW adjustment for age, gender, pathologic stage, CIS, variant histology, with 24-months RFS of 93% and 77%, respectively (p=0.01). 

RFS in MIBC

On multivariable analysis, as demonstrated below, odds of pT0N0 disease were significantly higher in the immunotherapy patients (OR: 3.8, 95% CI: 2.2 – 6.7).

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Based on these results, Dr. Nocera concluded that these findings suggest a potentially higher benefit of pembrolizumab with respect to the oncologic outcomes (both RFS and pathologic response), even after adjustment for potential confounders.

Presented by: Luigi Nocera, MD, Urology Resident Physician, Vita-Salute San Raffaele University, Milan, Italy

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023

References:
  1. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-66.
  2. Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol 2018 Dec 1;36(34):3353-3360.