presented the following case to facilitate the debate between Drs. Kassouf and Grivas titled: "In a patient who is pure UC, T2 disease; good GFR, should I go straight to radical cystectomy without neoadjuvant chemotherapy?" The patient case was as follows: 74 year-old-man, with a long-standing smoking history (otherwise healthy), normal renal function, who developed gross hematuria. He subsequently had a cystoscopy which demonstrated a 4-cm exophytic tumor on the left bladder wall and cytology positive for high-grade urothelial carcinoma. Upper tract imaging was negative and he was taken for a TURBT, which demonstrated T2 urothelial carcinoma, high-grade.
Dr. Grivas provided the rebuttal to Dr. Kassouf’s stance in favor of immediate radical cystectomy for T2 urothelial carcinoma by advocating for neoadjuvant chemotherapy prior to radical cystectomy. Looking again at the SWOG-8710 trial1, Dr. Grivas argues that neoadjuvant chemotherapy does, in fact, have benefit for T2 disease. There was a 30-month improvement in median OS (105 vs 75 months) for T2 stage disease, which in his opinion is comparable to patients with T3-T4a disease. Importantly, among the T2 patients included, in addition to a clear OS benefit, there was no higher toxicity or complication rates in these patients. Furthermore, there are no biomarkers for patient selection in these instances.
Dr. Grivas’ opinion of the EORTC 30894 (MRC) trial is much different than Dr. Kassouf’s in that T2 patients had an OS benefit, with no T2 patients showing increased toxicity or complications2. Once again, he cautions that there is no path stage ascertaining in patients who do not get a radical cystectomy and there are no biomarkers to guide treatment selection. Furthermore, in the ddMVAC trial by Plimack et al.3, 36% of patients were cT2N0M0. Overall, 38% demonstrated pT0 at cystectomy, and another 14% were downstaged to non–muscle invasive disease. Amongst cT2 patients, Dr. Grivas does caution that inaccurate staging very common.
Dr. Grivas concluded with several important take-home messages, defending the case for neoadjuvant chemotherapy among T2 bladder urothelial carcinoma patients.
- Neoadjuvant chemotherapy improved median OS including T2 patients in SWOG-87101. Accelerated/ddMVAC phase II trials and retrospective studies included T2 stage
- There is no molecular biomarker with proven clinical utility as of yet
- Neoadjuvant chemotherapy is routine practice, overall safe, with a manageable side effect profile with no negative impact on surgical morbidity or morbidity.
- There is a risk of broader under-utilization of neoadjuvant chemotherapy if we start splitting airs
- Posed in a question form: Are you comfortable depriving life-prolonging therapy of level I evidence, from large randomized phase III trials and meta-analyses from your patients?
- Until molecular profiling (eg. DDR gene mutations/GEP) may enable better patient selection in the future, we need to follow the current standard of care
Presented by: Professor Marek Babjuk, CSc, Motol Hospital, and Charles University, Prague, Czech Republic
Petros Grivas, MD, PhD, medical oncologist at Seattle Cancer Care Alliance, Clinical Director, Genitourinary Cancers Program, University of Washington Medicine, Associate Professor, Department of Medicine, Division of Oncology, University of Washington School of Medicine, Washington
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia Twitter: @zklaassen_md at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.
- Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-866.
- International Collaboration of Trialists, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011 Jun 1;29(16):2171-2177.
- Plimack ER, Hoffman-Censits JH, Viterbo R, et al. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol 2014 Jun 20;32(18):1895-1901.
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Read the Opposing Argument - Immediate Radical Cystectomy: In a Patient Who is Pure Urothelial Carcinoma T2 Disease with Good GFR