Dr. Feldman began by providing the rationale for trimodal therapy and bladder preservation in muscle-invasive bladder cancer (MIBC). He highlighted that organ conservation has become the standard of care for many malignancies including laryngeal carcinoma, anal carcinoma, breast carcinoma, esophageal carcinoma, and many limb sarcomas. However, in MIBC, radical cystectomy remains the most commonly used treatment approach. To date, while randomized controlled trials of radical cystectomy and trimodal therapy have been proposed and attempted, none have been successfully completed.
One of the strongest rationales for trimodal therapy is the burden associated with radical cystectomy. Dr. Feldman emphasized that nearly two-thirds of patients will experience a complication within 90 days of cystectomy, 26% will be readmitted, 13% will have a high-grade complication, and 2.7% will die. While there have been considerable efforts to reduce the burden of radical cystectomy through the use of enhanced recovery after surgery (ERAS) protocol and of minimally invasive surgical improvements, complications remain common. Further, cystectomy is associated with a decline in renal function in nearly three-quarters of patients with new-onset stage 3 CKD in approximately half.
In addition to the morbidity of radical cystectomy, population-based demonstrate that a large proportion of patients with MIBC do not receive curative-intent treatment. This effect is even larger among older patients. Thus, undertreatment of MIBC is common.
Dr. Feldman then highlighted guidelines from both the American Urological Association (AUA) and from the National Comprehensive Cancer Network (NCCN) which highlight that trimodal therapy is an accepted option in MIBC, with a category 1 recommendation in the NCCN guidelines for patients with cT2 disease and also those with cT3 and cT4a disease. Further, patient-facing resources from the AUA and BCAN highlight the potential for bladder preservation. Thus, it is important for urologists to understand the role of this treatment approach.
Dr. Feldman then emphasized that, when considering trimodal therapy, urologists play a critical role in terms of patient selection, TURBT and re-staging, and cystoscopic monitoring following treatment.
In terms of patient selection for TMT, he emphasized that the ideal candidate is completely resected following TURBT, has no hydronephrosis, no or minimal CIS, no prostatic urethral involvement, no high-grade tumor in diverticulae, and no upper tract involvement. However, he further pointed out that not everyone has to be the perfect candidate for TMT to be offered or to be suitable. Apart from these tumor factors, he highlights patient factors which are important including the ability to tolerate concurrent radio-sensitizing chemotherapy as well as being a suitable candidate for radiotherapy, including factors such as prior pelvic radiotherapy, inflammatory bowel disease, poor baseline bowel function, and poor baseline bladder function.
In offering TMT, Dr. Feldman emphasized the importance of coordinated, multi-disciplinary care involving urologists, radiation oncologists, and medical oncologists. In particular, he discussed the importance of communication between urologists and radiation oncologists with respect to tumor location and characteristics that may be only appreciable endoscopically. Indeed, this multi-disciplinary care has become the standard for patients with MIBC at most academic centers.
He further highlighted data from MGH which demonstrate the importance of TURBT in TMT outcomes: patients who have maximally complete TURBT as part of TMT had improved disease-specific survival compared to those who did not. This finding has since be corroborated in other datasets.
Dr. Feldman then highlighted technical aspects of TURBT, emphasizing that the goal is to remove all visible tumors. He further stressed the importance of performing repeat TURBT for cases of MIBC that have been referred following resection.
Following induction treatment, cystoscopy with repeat TURBT biopsy of the tumor site is advocated. This is the opportunity to ensure that no residual disease remains.
Following this talk, Dr. Efstathiou then presented the paradigm of TMT.
Presented by: Adam Feldman, MD, MPH, Urologist, Urologic Oncologist, Director, Combined Harvard Urologic Oncology Fellowship, Massachusetts General Hospital