Following Dr. Feldman’s introduction regarding the rationale for TMT, Dr. Efstathiou presented the Massachusetts General Hospital (MGH) TMT paradigm and outcomes. He began by discussing the two standard approaches to TMT for bladder preservation including split-course radiation or single-course radiation. He highlighted, as Dr. Feldman had done, that all approaches begin with maximal TUBRT. Regardless of the approach selected, he emphasized that (as shown in the figure below with yellow “U”s) the urologist remains the quarterback of care of these patients, even when patients opt for TMT.
While TMT has been employed for decades now, he described the evolution of this approach including changes in radiotherapy approaches and the concurrent chemotherapy prescribed.
The approach to bladder conservation has evolved over time with changes in both radiotherapy and chemotherapy approaches.
He then began to discuss the MGH TMT cohort and the outcomes. To date, this cohort comprises 475 patients accrued between 1986 and 2013. The majority (two-thirds) of patients have cT2 disease and the minority have either hydronephrosis (12%) or carcinoma in situ (24%). Due in large part to improving patient selection, but also attributable to improvements in radiotherapy delivery and chemotherapy efficacy, he showed that complete response rates have improved over time. In the most recent era, we can expect that 85-90% of patients may have a complete response to TMT. Improvements in the proportion of patients with a complete TURBT may also contribute to the improved outcomes seen.
Examining long-term survival outcomes he highlighted 5 and 10-year overall survival of 57% and 39%, respectively, with disease-specific survival of 66% and 59% over the same time frames. These rates, as expected, are significant modified by patient and tumor factors. In particular, patients with cT2 disease do somewhat better with disease-specific survival of 74% at 5-years and 66% at 10-years. In addition to these outcomes, utilization of salvage cystectomy has been declining over time such that it is now 15% or less, from more than 30% initially.
Clearly, patient selection forms a key aspect of ensuring good results. He showed data from the MGH series demonstrating that clinical T stage, hydronephrosis, tumor-associated CIS as well as treatment factors such as complete TURBT and response to chemoradiation predict long-term outcomes.
Presenting data from large cystectomy series, he suggested that the TMT data compare favourably to the outcomes observed following surgery. He presented population-based data published by Steve Williams and colleagues which showed improved survival for patients undergoing surgery but cautioned against interpreting these population-based studies on the basis of an inability to exclude patients medically unfit for surgery, the inadequacy of radiotherapy administered, and residual confounding. However, he highlighted other observational data including that from the Veterans Affairs dataset and a single-center propensity score-matched cohort from Toronto which showed equivalent outcomes for patients treated with TMT and radical cystectomy. Given that prior attempts at randomized controlled trials assessing this question have failed, he emphasized that he considers the Toronto data the best study available to guide treatment counseling.
Again using the MGH cohort, he presented data to suggest that the presence of variant histology doesn’t appear to change outcomes for patients receiving TMT. However, these data are limited as this is mostly based on urothelial carcinoma with squamous differentiation so may not be entirely generalizable to other variant histologies, including micropapillary, small cell, and others.
Beyond the comparison with cystectomy, Dr. Efstathiou emphasized that there is a huge unmet need for curative-intent treatment in MIBC as cystectomy is not being performed in up to 50% of older patients with MIBC. He suggested that TMT could fill that gap and be offered to patients who are currently not receiving curative-intent treatments. This is particularly notable as he showed data suggesting that increasing age does not appear to change the outcomes of patients undergoing TMT.
Dr. Efstathiou then discussed advances and evolutions in the techniques of radiotherapy delivery as they relate to TMT. In particular, the move from twice daily to daily radiotherapy has decreased patient burden. Further, more recently, many are now omitting the mid-treatment break for cystoscopic re-evaluation. However, there remain many relevant questions including that of the appropriate radiotherapy field (pelvic including nodes, bladder only, or tumor-focussed), the role for bladder filling, the role for hypofractionation, and the use of image-guided radiotherapy to facilitate tumor dose escalation.
Dr. Efstathiou then transitioned to Dr. Lee to discuss chemotherapeutic considerations in TMT.
Presented by: Jason Efstathiou, MD, DPhil, Director, Genitourinary Service, Department of Radiation Oncology, Clinical Co-Director, The Claire and John Bertucci Center for Genitourinary Cancers Multidisciplinary Clinic
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter during the AUA2021 May Kick-off Weekend, May 21-23, 2021