Neoadjuvant chemotherapy with gemcitabine and cisplatin followed by selective bladder preservation chemoradiotherapy in muscle-invasive urothelial carcinoma of bladder

Abstract

Purpose To assess the safety and efficacy of gemcitabine and cisplatin as neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive bladder cancer (MIBC). Materials and Methods Patients with clinical T2-T4aN0M0 MIBC eligible for radical cystectomy and cisplatin-based chemotherapy were treated with gemcitabine 1,000 mg/m 2 on days 1, 8 and 15, and cisplatin 70 mg/m 2 on day 1 every 28 days for 3 cycles. After clinical re-staging with computed tomography scans and cystoscopy, patients with clinical complete response (CR) were eligible to proceed without cystectomy and receive bladder preservation chemoradiotherapy involving weekly cisplatin 10 mg/m 2 and up to 70.2 Gy of radiation. The primary endpoint of the present prospective phase II study was metastasis-free survival (MFS). Results Between Oct 2017 and Nov 2019, a total of 138 MIBC patients were enrolled and treated with neoadjuvant gemcitabine/cisplatin. Neoadjuvant chemotherapy was well-tolerated, with fatigue, nausea, and pruritus being the most commonly observed adverse events. After completion of planned neoadjuvant chemotherapy, 54 patients with a clinical CR and 10 patients who did not have CR but refused surgery received bladder preservation chemoradiotherapy. With a median follow-up duration of 34 months (95% confidence interval [CI], 32%–36%), the 3-year MFS rate in 64 chemoradiotherapy patients was calculated to be 70% (95% CI, 58%–82%). Conclusions Neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy based on the clinical CR was feasible and efficacious in the treatment of MIBC.

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder

“…Among 30 patients with cCR after nivolumab plus NAC, 12 refused surgery but were treated with chemoradiotherapy. A possible explanation for the dropout rate is our internal protocol in which MIBC patients with a cCR after NAC could be offered bladder preservation chemoradiotherapy instead of cystectomy [16]. We found the observed DFS was impressive according to the achievement of a cCR after NAC, irrespective of subsequent therapies.…”

“…In 30 patients with a cCR, 12 refused surgery and were treated with chemoradiotherapy. Before commencing the bladder preservation chemoradiotherapy, our institutional guidelines recommended a maximal transurethral resection [16]. As a result, five of 12 patients who were treated with chemoradiotherapy had pathologic results: ypT0 (n=2), ypTis (n=2) and ypTa (n=1).…”

“…If a patient refused surgery, alternative treatment strategies per our institutional guidelines including bladder preservation chemoradiotherapy was offered [16]. Pre-and postsurgical tumor samples were collected for biomarker analyses.…”

“…A pCR was defined as no evidence of disease both in bladder and regional lymph nodes removed (i.e., ypT0N0) and determined by pathologic report conducted after surgery. Secondary endpoints included safety, clinical complete response (cCR; no visible tumor on imaging studies as well as on urine cytology and cystoscopy) to NAC [16], downstaging rate (i.e., <ypT1N0), disease-free survival (DFS), and PD-L1 expression. On the basis of our previous data [17], we hypothesized that a pCR <20% would suggest lack of activity, and an improvement in the pCR rate to at least 40% was considered to be of clinical interest.…”

Bladder-sparing strategies in patients with clinically localized muscle-invasive bladder cancer

“…Although radical cystectomy was associated with better OS in patients with cT3 disease [hazard ratio 0.42, 95% confidence interval (95% CI) 0.21−0.82, P = 0.01], the study showed no significant difference in 10-year OS between the approaches (40 versus 33%, P = 0.42) in the overall population after propensity-score matching [11 ▪ ]. In a phase II study of neoadjuvant CHT with gemcitabine/cisplatin followed by selective bladder preservation chemoradiotherapy (CRT), 54 out of 138 (39.1%) patients achieved CR with 3-year metastasis-free survival reaching 65% of the cases [12 ▪ ]. Furthermore, pooled data analysis of phase II/III trials launched by the Radiation Therapy Oncology Group (RTOG) resulted in a 5-year and 10-year cancer-specific survival (CSS) of 71 and 65%, respectively, and clinical CR of 39%, almost overlapping to those achieved by radical cystectomy [13].…”