ASCO GU 2021: Role of Definitive Local Therapy After Complete Clinical Response to Neoadjuvant Chemotherapy

(UroToday.com) In a plenary presentation in the Navigating Uncertain Times in Muscle-Invasive and Advanced Bladder Cancer session at the 2021 ASCO GU Cancers Symposium, Dr. Chad Ritch discussed the role of definitive, consolidative therapy following complete response to neoadjuvant chemotherapy.

Dr. Ritch emphasized that the opportunity for cure seldom comes twice. Thus, patient selection is key. He highlighted that the majority of patients with MIBC do not achieve complete response and that some patients with an apparent complete clinical response will have residual disease on final pathology. Current tools are insufficient to allow for accurate identification of complete clinical response. As a result, pathologic complete response is the best marker of long-term survival available.

Dr. Ritch cited SWOG data from Grossman and colleagues showing pathological complete response rates of 38% for neoadjuvant chemotherapy followed by cystectomy. In this seminal trial, those with a pathologic complete response had prolonged survival. However, Dr. Ritch emphasized that clinical trials may not reflect the “real world” given differences in patient characteristics, disease characteristics, and the time and nature of interventions and assessment which are standardized in trials. As a result, trial results may not be generalizable. Among large multi-center studies, the time between NAC and cystectomy ranged from 11 to 22 weeks whereas this was quite standard in the trial setting. Further, in real-world practice, pathologic complete response rates varied from 10 to 50%.

Further, Dr. Ritch highlighted discrepancies between apparent clinical complete responses and pathologic complete responses, with pT0 confirmed in only approximately two of three patients with clinical complete responses.

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Further data from the same group suggests false downstaging in 32%. Examining the test characteristics of post-NAC TURBT to predict pathologic pT0, there is high specificity (95%) but remarkably poor sensitivity (27%).

The concept of conservative management of complete responders is appealing given the potential to spare the morbidity of consolidative treatment. Initial reports suggested 5-year disease specific survival of 90% though this reflects significant selection bias.

Dr. Ritch then highlighted the rationale for radical cystectomy following complete response to NAC, emphasizing:

  1. the ultimate goal of treatment is improved long term survival, which may be better predicted in those with pT0;
  2. such treatment eliminates the risk of local recurrence and the need for further local intervention;
  3. we avoid much of the uncertainty associated with surveillance following cCR including surveillance cystectomy, given the limitations of imaging and biomarkers to date.
Further, Dr. Ritch emphasized that data from the Nordic trials of radical cystectomy with or without NAC show that patients with a complete response pre-surgery have the best long-term outcomes, a finding supported by observational research as well.

Dr. Ritch then discussed the potential role of partial cystectomy emphasizing the ability to obtain pathologic confirmation without the morbidity of radical cystectomy. However, he emphasized that this should only be considered in very select candidates and that there are concerns about oncologic efficacy. He highlighted data in which 15 patients at MSKCC underwent partial cystectomy among 111 who achieved cT0 following NAC with MVAC with 10-year overall survival of 73% and bladder intact survival of 53%. Dr. Ritch then described a recent “tetramodal therapy” trial among 154 patients in which they received TRUBT + chemotherapy + radiotherapy + partial cystectomy with pelvic lymphadenectomy. This approach was associated with a 71% cCR and pT0 among 90% of those who underwent resection. 


Presented by: Chad Ritch, MD, MBA, Urologic Oncology, University of Miami Health System

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
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