ASCO GU 2021: Uncertainties in the Optimal Delivery of Trimodality Therapy

( In a plenary presentation in the Navigating Uncertain Times in Muscle-Invasive and Advanced Bladder Cancer session at the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Hoskin discussed uncertainties in trimodality therapy (TMT) for muscle invasive bladder cancer (MIBC).

Dr. Hoskin began by discussing the approach to TMT. TMT is a treatment approach to bladder cancer treatment using TURBT, radiotherapy, and chemotherapy to provide bladder preserving treatment. In general, the elderly, the frail and infirm, those with poor performance status, and those with comorbidities receive TMT in his view though he emphasized that we don’t really know the population-level characteristics of patients who receive this approach. He emphasized that, despite NCCN and EAU endorsement, there is a perception of urologic incredulity with respect to radiotherapy in MIBC. In part, the failure of biomarkers to identify patients who are suitable for particular MIBC treatment approaches has furthered this issue in Dr. Hoskin’s view.

Dr. Hoskin then discussed the role of neoadjuvant chemotherapy (NAC) for patients undergoing TMT. While there is a clear and established role for among patients opting for radical cystectomy, it is somewhat less clear that this is beneficial in patients undergoing radiotherapy. However, in the BA06 30984 trial demonstrated similar improvements in NAC for patients undergoing radiotherapy though the RTOG 8903 study, while small, failed to find a benefit.

Moving forward, Dr. Hoskin discussed the need for maximal debulking with TURBT as a component of TMT. While this is often cited, there is relatively poor evidence to support this. In the BC2001, only 50% of patients actually had complete TURBT. Thus, whether it is important or not, it is not routinely performed. A post hoc analysis of the BCON trial demonstrated no difference in overall survival whether patients received complete resection or simply biopsy.

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Finally, Dr. Hoskin discussed the optimal approach to delivering radiotherapy. A recent assessment of fractionation based on the BC2001 and BCON trials demonstrated that there is an advantage to the use of a moderately hypofractionated 55 Gy regime compared to conventionally fractionated 64 Gy regimes. Further, there was no excess toxicity with this hypofractionated schedule. 

Further, TMT typically utilizes radio-sensitizing chemotherapy based on data from BC2001 though data from BCON suggested that hypoxia modification may confer a similar benefit. Notably, there are markers which may allow identification of patients who are most likely to derive benefit from hypoxia modification. Finally, there is an ongoing interest in the role of immunomodulation in the context of TMT with at least 25 ongoing clinical trials on the basis that radiotherapy may induce immunogenic cell death and active the innate immune system. However, there are concerns related to bowel-related toxicity with this combined approach.

Presented by: Peter Hoskin, MD, FCRP, FRCR, Professor, Urologist, Mount Vernon Cancer Centre, Universirty College of London, Machester, United Kingdom

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Contact: @WallisCJD on Twitter during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021