A recent systematic review and meta-analysis of 19 studies and 12,380 subjects assessing radical cystectomy compared to combined modality treatment for MIBC showed no difference in OS at 5 years (HR 0.96, 95%CI 0.72-1.29) or 10 years (1.02, 95%CI 0.73-1.42) , thus solidifying bladder sparing, multi-modal therapy as a legitimate treatment option for MIBC.
Dr. Hoskin feels there are several challenges moving forward:
- Can we identify patients who may not do well with non-surgical treatment?
- Do poor responders to radiotherapy respond better to surgery?
- Do poor responders require specific modification of radiotherapy: chemoradiation or bladder carbogen nicotinamide (BCON)
MRE11 expression has also been used to predict patients that may do better with radical cystectomy when compared to radiotherapy. Specifically, patients with low MRE11 expression do better undergoing cystectomy compared to those undergoing radiotherapy, whereas patients with high MRE11 expression fair better with radiotherapy. Unfortunately, several small studies have not demonstrated a benefit for hypoxic tumors responding to radical cystectomy.
Whether poor responders require specific modification of radiotherapy has been assessed in a recent study looking at a benefit of hypoxia modification of radiotherapy for high risk bladder cancer patients . Among BCON high hypoxia patients, those receiving radiotherapy + BCON had significantly improved local relapse-free survival compared to radiotherapy alone, although these outcomes did not remain consistent in low-hypoxia patients. Similarly, there has been no benefit for adding BCON to radiotherapy for patients with basal vs luminal subtyped tumors.
Dr. Hoskin concluded with several take-home points:
- At this point we can in fact identify patients who may not do well with non-surgical treatment
- Poor responders to radiotherapy may benefit more from surgery when stratifying by MRE11 expression, although this not seen when assessing hypoxia
- Poor responders do in fact require specific modifications of radiotherapy, notably with the addition of BCON in the setting of hypoxia
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre @zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA
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