Dr. Umbas began with showing data from the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) database demonstrating that the percentage of patients above the age of 70 that undergo radical cystectomy is much smaller than that of patients under the age of 70.1,2 Additionally, he presented data from the Memorial Sloan Kettering Cancer Center (MSKCC) on more than 1140 patients that had undergone radical cystectomy between 1995-2005. According to this large single-institution data, the probability of 90-day mortality after radical cystectomy significantly rises with age (Figure 1). 3 Using the age cutoff of 75, published data have shown that the overall survival is also significantly worse for patients older than 75 who undergo radical cystectomy.4
Figure 1 – Increasing 90-day mortality after radical cystectomy rising with age:
According to the latest National Comprehensive Cancer Network (NCCN) guidelines, bladder preservation following maximal TURBT with concurrent chemoradiotherapy is a valid therapeutic option for MIBC. Bladder-sparing treatment, more known as the trimodal therapy, consisting of maximal TURBT, chemotherapy, and radiotherapy, can be performed in one of two main strategies – the split and the continuous course. In the continuous course, after maximal TURBT, maximal radiotherapy with full dose chemotherapy is given to the patient, which is then assessed with cystoscopy and biopsies. If there is evidence for complete response, the patient is put on surveillance, while if there is an incomplete response, radical salvage cystectomy is performed. In contrast, in the split course, after maximal TURBT, the patient is first given induction radiation to about 40 Gy, together with chemotherapy. The patient is then reexamined with cystoscopy and biopsies. If a complete response is noted, the patient continues to receive consolidation radiotherapy and concurrent chemotherapy. However, if there is an incomplete response, radical salvage cystectomy is performed.
Results from various studies examining tri-modal therapy have shown a 5-year overall survival rate of approximately 50%. A large propensity-matched comparison of patients undergoing radical cystectomy and trimodal therapy was published by the group in Princess Margaret Cancer Center in 2017.5 Patients who were candidates for trimodal therapy were those with a solitary tumor less than 5 cm, with either no or minimal hydronephrosis, with good bladder function, and no multifocal carcinoma in situ (CIS). The study showed similar overall survival in both groups of patients, those who received trimodal therapy and those who underwent radical cystectomy. Similar results were demonstrated in a large population-based study from the NCDB showing no difference in the overall survival rates. 6 In a systematic review and meta-analysis based on 11 studies between 2009-2017, no differences in overall survival and progression-free survival between radical cystectomy and trimodal therapy were found.7
In the most recent European Association of Urology (EAU) guidelines, tri-modal therapy is one of the optional treatments recommended for MIBC, especially for patients who are not fit for radical cystectomy. The best way to assess patients who are not fit for radical cystectomy is by using the frailty index. This index is based on functional status, history of diabetes, chronic obstructive pulmonary disease, congestive heart failure, and hypertension. This is a superior method of evaluating the ability of an elderly patient to withstand the rigors of surgery, compared to other more traditional methods. 8
In summary, bladder-sparing therapy is a valid option in MIBC patients who want to preserve their native bladder, or who are unfit to undergo radical cystectomy. However, it should be offered only for well-selected patients with several mandatory criteria. These include patients that can successfully undergo maximal TURBT, who harbor no more than a T2 disease without CIS, and who have mild to moderate hydronephrosis. Most importantly these patients need to be compliant with a strict follow-up protocol entailing routine cystoscopies and biopsies.
Presented by: Rainy Umbas, MD, University of Indonesia, Indonesia
References:
1. Smith AB et al. BJU Int 2014
2. Liberman D et al. Urology 2011
3. Taylor JM et al. BJU Int. 2012
4. Chan ES et al. Hong Kong Med J. 2013
5. Kulkarni G et al. J Clin Oncol 2017
6. Zhong et al. Am J Clin Oncol 2018
7. Garcia-Perdomo HA et al. World Journal of Urology 2018
8. Sathianathen NJ et al. Eur Urol 2018
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre Twitter: @GoldbergHanan at the 38th Congress of the Society of International Urology - October 4- 7, 2018 - Seoul, South Korea
Further Related Content:
MRI Should Be Performed in All Patients Before Biopsy: Bladder Sparing Surgery – CON