Editor’s Note: The ASCO-GU 2024, a major event in the field of urologic oncology, was held in San Francisco, USA, showcasing numerous innovative research advancements and discussing future treatment directions for urologic and male reproductive system tumors. For patients with non-muscle invasive bladder cancer (NMIBC) who do not respond to Bacillus Calmette-Guérin (BCG) treatment, there remains a need to find effective tools to detect the risk of recurrence or progression after second-line bladder-sparing treatments. During the conference, Professor Marie-Pier St-Laurent from the University of British Columbia presented the latest advancements in using whole-genome analysis of urinary tumor DNA (utDNA) to identify minimal residual disease (MRD) and quantify genomic changes, sharing in-depth insights in an interview with Oncology Frontier.
Oncology Frontier: Could you please briefly introduce the research you shared at ASCO-GU?
Professor Marie-Pier St-Laurent: The study presented at this conference analyzed utDNA from the SWOG 1605 study cohort with whole-genome analysis. The goal was to determine if utDNA could predict recurrence in NMIBC patients who do not respond to BCG treatment and are treated with atezolizumab. The findings indicated that patients with positive utDNA at baseline were almost three times more likely to experience recurrence within 12 and 18 months compared to those with negative utDNA. The study demonstrated that utDNA could detect tumor mutations associated with minimal residual disease (MRD) even in patients who tested negative in cystoscopy and cytological examinations. This research can further guide subsequent studies and clinical practices, such as detecting recurrences not found by current standard protocols through bladder biopsies.
Oncology frontier : Please brief your abstract presented during ASCO GU.
Dr. Marie-Pier St-Laurent: Our study, derived from SWOG 1605, investigated urine tumor DNA (utDNA), aiming to determine if this test could predict recurrence in patients treated with atezolizumab for BCG-unresponsive NMIBC. Our findings revealed that patients testing positive for utDNA at baseline were almost three times more likely to experience recurrence within 12 and 18 months compared to those testing negative. Interestingly, this test helped identify minimal residual disease (MRD) in patients showing no disease via cystoscopy and cytology but having high tumor mutations in their urine. This could guide further investigations, such as bladder biopsies, to detect recurrences not identified by current standard methods.
Oncology Frontier: For high-risk NMIBC, the standard treatment is transurethral resection of bladder tumor (TURBT) followed by post-operative BCG infusion. However, about one-third of the patients do not respond to BCG. What are the subsequent treatment strategies for these patients?
Professor Marie-Pier St-Laurent: For patients who do not respond to BCG, the current standard treatments usually include options like cystectomy. However, due to the associated risks, many patients opt for alternative treatment strategies, depending on the availability of medications in their country/region. Although the complete response rates are relatively low, pembrolizumab has been approved by the FDA for treating high-risk NMIBC and has shown some effectiveness; it was not subject to prospective studies at the time but is often used due to its lower cost. If patients refuse cystectomy, they are typically advised to participate in clinical trials to access more treatment options. The SWOG 1605 study indicated that atezolizumab treatment for six months had a better complete response rate than pembrolizumab, but it has not been approved by the FDA due to trial standards and other reasons.
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Oncology Frontier: The standard treatment for high-risk NMIBC is transurethral resection of bladder tumors (TURBT) and postoperative infusion of BCG, but nearly one-third of patients do not respond to BCG. What are the follow-up treatment strategies for these patients?
Dr. Marie-Pier St-Laurent: For BCG-unresponsive patients, the standard of care usually involves cystectomy. However, due to associated risks, many patients opt for alternative treatments, depending on availability in their country. Pembrolizumab has been approved and shows some response, albeit with a lower complete response rate. Researchers not studied prospectively in past, but pembrolizumab is often used due to its lower cost. If cystectomy is declined, clinical trials are recommended, offering various treatment options. Atezolizumab, as investigated in SWOG 1605, displayed better complete response at six months than pembrolizumab, but it was not approved by the FDA due to the trial’s criteria.
Oncology Frontier: At the ASCO GU conference, you discussed the genomic characteristics of patients who did not respond to BCG and were treated with atezolizumab. Are there any biomarkers that could potentially predict treatment efficacy or help select appropriate patients?
Professor Marie-Pier St-Laurent: We analyzed urinary tumor DNA (utDNA) as a potential biomarker. Currently, there are no biomarkers that definitively demonstrate the ability to predict treatment responses. The field is actively researching various biomarkers, including circulating tumor DNA (ctDNA) in the blood, although its study in NMIBC is not common. There is a promising outlook for research in this area, and we are hopeful that effective biomarkers will emerge in the future to improve patient survival.
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Oncology Frontier: You announced the genomic characteristics of BCG non-responsive patients after atezolizumab treatment at the ASCO GU conference. Are there any biomarkers that can be used to predict the efficacy or screen suitable patients?
Dr. Marie-Pier St-Laurent: We’ve examined urine tumor DNA as a potential biomarker. Currently, no biomarker has conclusively shown the ability to predict treatment response. The field is actively studying various biomarkers, including circulating tumor DNA (ctDNA) in blood, though it’s not commonly studied in NMIBC. The ongoing research in this area is promising, and we anticipate future developments.
