Combined Modality Bladder-Sparing Therapy for Muscle-Invasive Bladder Cancer: How (Should) We Do It? A Narrative Review

Abstract

Organ-sparing combined-modality treatment for muscle-invasive bladder cancer remains underutilized despite high-quality evidence regarding its efficacy, safety, and preservation of quality of life. It may be offered to patients unwilling to undergo radical cystectomy, as well as those unfit for neoadjuvant chemotherapy and surgery. The treatment plan should be tailored to each patient’s characteristics, with more intensive protocols offered to patients who are fit for surgery but opt for organ-sparing. After a thorough, debulking transurethral resection of the tumor and neoadjuvant chemotherapy, the response evaluation should trigger further management with either chemoradiation or early cystectomy in non-responders. A hypofractionated, continuous radiotherapy regimen of 55 Gy in 20 fractions with concurrent radiosensitizing chemotherapy with gemcitabine, cisplatin, or 5-fluorouracil and mitomycin C is currently preferred based on clinical trials. The response should be evaluated with repeated transurethral resections of the tumor bed and abdominopelvic-computed tomography after chemoradiation, with quarterly assessments during the first year. Salvage cystectomy should be offered to patients fit for surgery who failed to respond to treatment or developed a muscle-invasive recurrence. Non-muscle-invasive bladder recurrences and upper tract tumors should be treated in line with guidelines for respective primary tumors. Multiparametric magnetic resonance can be used for tumor staging and response monitoring, as it may distinguish disease recurrence from treatment-induced inflammation and fibrosis.

Prognostic Value of Postneoadjuvant Chemotherapy Neutrophil-to-Lymphocyte Ratio in Patients undergoing Radical Cystectomy

“…In terms of CRT, an advanced bladder cancer (ABC) meta-analysis including 2688 participants showed that the survival benefit of platinum-based NAC persisted irrespective of further treatment, including RC, radiotherapy, or CRT. The results of this meta-analysis are consistent with a previous randomised controlled trial (RCT) [3,5,6]. Regardless of treatment after NAC administration, the response mainly depends on the chemotherapy regimen offered.…”

Bladder Only Radiotherapy Concurrent with Chemotherapy Outcomes in Muscle Invasive Bladder Cancer Management: Our Institute Experience

“…Findings from previous studies reported LN relapse rate in patients receiving radical bladder RT to range between 4% and 14% regardless pelvic LN was included in RT field or not. Data from pooled RTOG analysis showing that the rate of 5-year distant metastasis is 32% while locoregional recurrence rate varies between 12 and 16% (10,11) .…”

“…Several radiosensitizing chemotherapy for trimodality therapy have been developed with lack of evidence to recommend an optimal choice of a radiosensitizer, as they have not been compared in randomized trial. Cisplatin is a reasonable option for patients fit for cisplatin (11) . Most of our patients (89%) received cisplatin concurrent with RT with the remaining (11%) received cisplatin with reduction due to toxicity.…”

Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes

“…This, in conjunction with a resection of the primary bladder cancer site, is vital. The absence of LN metastasis and downstaging to <ypT2 paves the way for the possible implementation of trimodal therapy (TMT) [17]. The decision between opting for the RC and TMT is a shared decision.…”