SUO 2018: Before and After Clinical CR from NAC

Phoenix, Arizona ( Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or chemoradiation is the standard of care for urothelial carcinoma in patients with muscle-invasive bladder cancer (MIBC). Both cystectomy and chemoradiation carry potential short and long-term toxicity and quality of life implications. Sparing patients RC or chemoradiation after NAC without compromising oncologic outcomes would improve quality of life and decrease morbidity.

At the Bladder Cancer Session II, during a Panel discussion on bladder preservation - at SUO 2018, Dr. Phillip Abbosh, MD, PhD, a urologic oncologist and a surgeon-scientist at Fox Chase Cancer Center, gave his talk on Before and After Clinical Complete Response from Neoadjuvant Chemotherapy.

Dr. Abbosh started his talk by asking two most critical questions that will prevent patients from undergoing RC 1) Who is going to respond? , and 2) Who actually responded? These can be studied by looking at pre-chemotherapy tissue or other diagnostic analytes. Recent work has shown that mutations in DNA damage repair/response genes are predictive of pathologic response to NAC at the time of RC, with those patients achieving pT0 disease demonstrating excellent long-term survival. Post-chemotherapy tissue sampling includes the search for dynamic biomarker which will be negative after treatment response. He mentioned that most of the studies have been retrospective and looked at histopathology of the biopsy specimen after chemotherapy, but 25-50% of cT0 patients fail this management algorithm. It is not clear if this is because of failure to detect or growth of new tumors.

Dr. Abbosh then highlighted the two clinical trials undergoing at Fox Chase Cancer Center to identify patients who can be exempt from RC. The first clinical trial is looking at cystoscopy evaluation and bladder mapping right before RC, and the primary outcome measure will be the negative predictive value of systemic biopsy. This removes the selection bias of previous studies. The second trial is called the RETAIN trial, which was recently featured in The Washington Post, and incorporates DDR mutations into surgical planning. Patients who respond to NAC may be exempt from RC, and the primary outcome will be metastasis-free survival at two years. He presented the trial design for both these remarkable studies, and the blood, tissue and urine samples collected from each patient on this trial will allow for identification of any biomarkers of response.

Dr. Abbosh concluded his talk by summarizing his research interest looking at the mutational clearance from urine by performing deep sequencing from isolated DNA from urine samples, and this correlates well with complete response to NAC. He welcomes collaboration in this fascinating area of research.

Presented By: Phillip Abbosh, MD, PhD, Fox Chase Cancer Center, Philadelphia, PA


Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA, @shekabhishek, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona