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Imperative Paradigm Shifts at ASCO GU 2023: Health Equity, De-escalation of Surgery and the De-escalation of Manels

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The meeting of the genitourinary branch of the American Society of Clinical Oncology (ASCO) never fails to disappoint, and ASCO GU 2023 was no exception. As a urologist and soon-to-be urologic oncologist, I attended ASCO GU to learn about the latest practice-changing updates and pivotal clinical trial results directly from the source. The multidisciplinary nature of GU ASCO stands out from other society conferences, with presenters and attendees ranging from basic scientists to clinicians from specialties including medical oncology, radiation oncology, and urologic oncology. This presents a unique opportunity to examine oncologic patient care through multiple lenses. In other words, this is a space where you can attend a plenary session with your radiation oncologist colleague and listen to interim results of the PACE trial (NCT01584258) of SBRT vs surgery for localized prostate cancer (true story). Hopefully you’ll remain friends afterwards. 

A prominent topic at ASCO GU this year that deserves recognition and applause was health equity. An all-star panel of speakers emphasized strategies to equalize the race and gender gap in treatment outcomes and to promote inclusion and diversity in clinical trials. Dr. Christine Ibilibor MD (University of Virginia) delivered a phenomenal presentation on gender-based and race-based disparities, describing an interplay of patient-related, provider-related, and system-related issues. This discussion was sobering but highly insightful, as Dr. Ibilibor presented evidence describing treatment delay, less guideline-based care, and decreased overall survival in Black/African American and Hispanic patients with urothelial carcinoma. Dr. Elad Sharon MD, MPH (National Cancer Institute) discussed the need to expand clinical trial eligibility criteria in order to accrue more diverse patients. These measures include eliminating certain laboratory-based exclusion criteria that have no scientific relevance or safety concerns, as these stringent criteria are more likely to exclude non-Caucasian patients. Dr. Vidit Sharma MD (Mayo Clinic) delivered a thoughtful presentation on cost effectiveness in bladder cancer, presenting data suggesting that Black race, lack of college degree, younger age, insurance status, employment, and income are associated with financial toxicity in bladder cancer management.  Health equity should be a primary consideration in clinical care decisions and future clinical trial design. 

The bladder cancer session on day 2 was enlightening and thought-provoking. One recurrent topic was the utilization of genomics for risk stratification and prognostication in urothelial carcinoma. Another popular topic this year was de-escalation in surgery, including salvage intravesical options to delay or obviate the need for radical cystectomy for high-risk BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC), and the bladder-sparing approach in patients with muscle-invasive bladder cancer (MIBC). Of note, the current gold-standard management for MIBC is neoadjuvant cisplatin-based chemotherapy followed by extirpative radical cystectomy. As a surgeon with a strong interest in bladder cancer, my usual go-to emotion when providers hate on radical cystectomy ranges from cautious skepticism to mounting wrath, depending on the clinical scenario. However, I kept an open mind during the plenary sessions and emerged with a few important takeaways. The RETAIN (risk-enabled therapy after initiating neoadjuvant chemotherapy in bladder cancer) phase II trial (NCT02710734) combined both topics of genomics and bladder-sparing treatment. In this noninferiority trial, the presence of DNA damage response (DDR) gene mutations (ATM, ERCC2, FANCC, or RB1) was used to select patients for a risk-adapted approach for MIBC. Existing evidence has suggested that these mutations predict a good response to neoadjuvant chemotherapy. Thus, trial patients with a mutation of interest plus no residual tumor (cT0) after neoadjuvant chemotherapy were assigned to active surveillance rather than radical cystectomy. Results of this risk-adapted approach failed to meet the non-inferiority condition and therefore the evidence did not support active surveillance after neoadjuvant chemotherapy for these patients. The concept of de-escalation in cancer surgery is well established in breast cancer literature. However, the evidence in urothelial carcinoma reveals that despite early optimism regarding the prognostic potential of DDR alterations, contemporary evidence from 2022 published years after the RETAIN trial initiation suggest no predictive value of ATM, FANCC, RB1, or ERCC2 for response to chemotherapy. These negative trial findings are nevertheless important, as they illustrate that future research should focus on refining patient selection for surgery de-escalation measures. This also reveals a need for additional validation of genomic data in larger and more diverse cohorts for risk stratification purposes. Until we obtain substantial evidence to support alternative management approaches that deviate from the gold standard, future trials advocating for a less aggressive alternative therapy should ideally enroll only patients who are ineligible for or refuse the standard-of-care approach. While the decision to operate on a poor surgical candidate may often be detrimental, the failure to perform an evidence-based operation on an eligible patient may miss an important window of opportunity.

From a bird’s-eye view of ASCO GU 2023, one of the most pivotal paradigm shifts of all was the departure of the “manel.” This term refers to an all-male speaking panel that has become a marker of gender inequity in academia. A notable European Urology publication found that 86.8% of faculty speakers at a major urological conference were male, and 63.5% of sessions were “manels.” I remember fondly my first ASCO GU meeting on February 14th 2019. I was a young and impressionable urology resident with secret aspirations of a career in urologic oncology but was, in retrospect, subconsciously discouraged by the low female speaker representation, particularly among surgical faculty. That day, I sent a photo of a manel partially obstructed by a sea of predominantly male attendees to my best friend, a female dermatologist. “This conference looks like all men. No wonder it’s on Valentine’s Day. Derm would never hold a conference on Valentine’s Day,” to which I responded, “Onc gives zero shirts* about Valentine’s Day.” Flash forward to ASCO GU 2023 four years later: I was pleasantly surprised that a majority of panels were diverse, well-balanced between genders, and inclusive of both junior and senior faculty. I hope and optimistically anticipate that this trend will continue as we learn from the best and brightest voices. In an ideal world, we should all give some shirts* about Valentine’s Day.

Dr. Zhang has no conflicts of interest to report.

Illustration by April Brust

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