Society of Urologic Oncology (SUO) 21st Annual Meeting

SUO 2020: Optimizing Management of High Risk Non-Muscle-Invasive Bladder Cancer – Case Based Discussion

(UroToday.com) The plenary session of the last day of the 2020 Annual Meeting of the Society of Urologic Oncology (SUO) began with a panel discussion stepping through the case of a patient with non-muscle invasive bladder cancer.


Dr. Sima Porten, the moderator, introduced the case: a 60-year-old otherwise healthy male with high-volume high-grade Ta urothelial carcinoma of the bladder diagnosed on an initial transurethral resection (TUR) with no muscle in the initial specimen.

The panel first addressed the question of perioperative chemotherapy for this patient. There was immediate resounding consensus that, based on the results of SWOG S03371 that the panelists would administer perioperative intravesical gemcitabine to this patient assuming there was no concern for perforation. There is some uncertainty regarding the benefit of this, as the SWOG trial primarily targeted patients with low-grade disease, however, given the favorable side effect profile of gemcitabine, the inclusion of many patients with high-grade cancer in the trial, and the inability to tell grade from gross inspection alone, the panelists all favored use of gemcitabine after most first resections. All have abandoned the use of mitomycin in this setting due to a belief in the more favorable side effect profile of gemcitabine.

Even stronger consensus was noted regarding the need for re-resection in this patient. Though guidelines do not require re-resection in all patients with HGTa, the high volume of initial disease and lack of muscle in the initial resection specimen would have independently been sufficient to merit a second resection in most panelists’ eyes, and the combination made that decision unequivocal, though Dr. Sumeet Bhanvadia suggested there might be a role for office blue light cystoscopy to rule out the need for a second resection if there was a desire to avoid another anesthetic. Dr. Sarah Psutka emphasized the importance of a bimanual examination as part of a high-quality re-TUR, and also recommended that blue light be used during the TUR if available, citing an ~25% rate of missed tumors on white light only cystoscopy.

Key points from this part of the case were:

  • Recommendation for perioperative chemotherapy at initial TUR
  • The need for high-quality TURBT with consideration of advanced cystoscopy
  • Mandatory nature of re-resection of HGT1 disease
  • Highly-encouraged nature of re-resection of HGTa disease, especially if high volume
  • Need for adequate sampling of the detrusor muscle

This patient was found on re-TUR to have a blue-light positive lesion which was ultimately found to be carcinoma in situ (CIS) along with some residual HGTa.

There was universal agreement that the next step for this patient should be BCG induction followed by maintenance, as the presence of concomitant CIS rendered the patient “high risk” by America Urological Association guideline criteria. Dr. Janet Kukreja reviewed options for this patient in the setting of recent BCG shortages including:

  • Dose reduction – ½ or 1/3 dose at each BCG session
  • Abbreviated maintenance (1 vs 3 years)
  • Clinical trials – e.g. SWOG 1602
  • Intravesical chemotherapy – including optimized mitomycin or gemcitabine/docetaxel
  • Cystectomy in select populations

Multiple panelists strongly recommended starting a discussion about cystectomy at this point, even though most would not consider it as the preferred option, with Dr. Bhandavia citing a 50% recurrence rate for CIS even with favorable initial responses to BCG. Multiple panelists cited enrollment in SWOG 1602 as being critical in obtaining BCG for their patients, though this will complete accrual very shortly.

The patient received induction followed by maintenance BCG, but had significantly lower urinary tract symptoms. After the first complete round of maintenance BCG, a patch of erythema was noted on cystoscopy. This was biopsied in the office and found to be CIS.

Dr. Kukreja began by noting that this patient now meets the criteria for BCG unresponsive disease. The two currently available therapies for this are intravesical chemotherapy and systemic pembrolizumab, with data supporting the use of intravesical vicinium and intravesical nadofaragene firadenovec likely to lead to FDA approval of these therapies in the near future.

All the panelists agreed that the patient should be offered cystectomy again. None felt strongly that this was a preferred option, but several pointed out that choosing cystectomy in this setting is often unfairly stigmatized in the urologic community.

Drs. Kukreja, Bhanvadia, and Psutka all chose intravesical gemcitabine and docetaxel as their preferred next line agent, citing a favorable side effect profile and a ~50% two-year recurrence-free survival ratel in retrospective series. Dr. Murray and Dr. Porten chose pembrolizumab, citing high-quality prospective data, United States Federal Drug Administration (FDA) approval for this indication, and immediate availability of expert medical oncologists in their practice setting. Most agreed that if CIS were to persist following a complete course of either of these agents, cystectomy would be the clear next choice.

Dr. Porten concluded the talk by revealing the resolution of the case: the patient received pembrolizumab, but had a recurrence of CIS at 6 months. He then opted to try intravesical gemcitabine and docetaxel and received induction followed by maintenance treatments until he developed recurrence with imaging showing a suspicious lymph node. He received neoadjuvant chemotherapy followed by cystectomy, which revealed ypTisN0 disease. He remains free of disease with 1 year of follow up.

Moderator: Sima Porten, MD, MPH, Associate Professor, Department of Urology, University of California San Francisco
Panelists:
Sumeet Kaur Bhanvadia, MD, Urologic Oncologist, Keck School of Medicine, University of Southern California
Janet Baack Kukreja, MD, MPH, Assistant Professor, Surgery-Urology, Urologic Oncologist, University of Colorado Denver
Katie S. Murray, DO, MS, FACS, Assistant Professor at the University of Missouri Department of Surgery-Urology Division. She is the medical director of Urological Oncology at Ellis Fischel Cancer Center in Columbia, Missouri.University of Missouri
Sarah P. Psutka, MD, MS, Urologic Oncologist who serves as an Assistant Professor for the Department of Urology at the University of Washington Medical Center



Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA, @mcstroth during the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC

 

References:

1. Messing EM, Tangen CM, Lerner SP, et al. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non–Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. JAMA. 2018;319(18):1880–1888. doi:10.1001/jama.2018.4657

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