Multimodal Management of Invasive Bladder Cancer in the Elderly

Acapulco, GRO, Mexico (UroToday.com) Life expectancy in general population is increasing, making more frequent the presentation of bladder cancer in the elderly population. The treatment for octogenarians is the same, cystectomy and perioperative chemotherapy in selected cases, nevertheless, there are more conservative options such as partial cystectomy, transurethral resection of the bladder (TURB) plus chemotherapy, radiotherapy alone and trimodal therapy (TMT). Wassim Kassouf, MD emphasized that chronological age alone should not be used to exclude patients from definitive therapy, the appropriate decisions should incorporate the functional status and comorbidities, patient desire and goals, and informed understanding of the risk and benefits.

The cystectomy is a procedure with high morbidity and mortality. The percentage of complications presented during the first 90 days after surgery is 67, as reported by Shabsigh et al in 2009. So far the advances in technology haven’t changed the paradigm. All randomized studies comparing robotic vs open surgery were done with a hybrid approach, intracorporeal diversion trials are still running. The only benefit demonstrated is in less bleeding. 

The neoadjuvant chemotherapy (NAC) has improved survival from 45% to 50% at 5 years.  Although, when it comes to the octogenarians, it´s a problem still unsolved. There aren´t any level I evidence studies about this asset, since these patients were systematically excluded from the SWOG and MRC studies, and toxicity in this group of patients hasn’t been clearly defined, with toxic deaths approximately between 2.3 - 4.6%. This raises worries about adding morbidity when combining NAC and cystectomy.

In the USA, only 18% of octogenarians undergo cystectomy, 46% receive QT and RT, and 60% surveillance, the former percentage remarks the need for optional therapies in patients unfit for surgery.  The TMT is gaining acceptance in patients who are not surgical candidates or who refuse surgery, incorporating maximal TURB, radiation, and chemotherapy as a radiosensitizer. The response to TMT has increased over all these years with a current rate of complete response of 86.1%, in contrast to 64.5% in 1986, and the key factor is patient selection. Nowadays, the trials include patients with better condition and disease in less advanced stages. Efstathiou et al, published in 2012 a cancer-specific survival (CSS) of 64%, and only 29% had to undergo cystectomy. 

About the chemotherapy as a radiosensitizer in TMT, it has probe in randomized study to improve CSS and overall survival (OS) in comparison with radiotherapy alone (Fig 1), and there aren’t differences between the use of Cisplatin/5FU or a low dose of Gemcitabine, both with RT, as was shown in a randomized phase II multicenter trial published by ASCO 2018. Even when the TMT is a well established less-invasive option, it does not preclude complications, and severe toxicity has been reported in 7% of the patients, including 2% of salvage cystectomy due to contracted bladder, 1.5% bowel obstruction requiring surgery, and 3% who developed severe frequency due to reduced bladder capacity. As before, the best way to avoid these complications is the adequate selection of patients, and some factors have been associated with favorable oncologic outcomes, those are: Organ confined tumor (cT2) and less than 5cm, ability to remove all visible tumor with TUR, absence of hydronephrosis, absence of extensive CIS or diffuse multifocal disease, adequate bladder capacity and function, tumor with  urothelial histology and Dr Kasouff strong recommend routine re-biopsy post TMT and prompt salvage cystectomy for nonresponders or recurrences.       

UroToday SMEO2018 Multimodal Management of Invasive Bladder Cancer in the Elderly

The recurrence after complete response to TMT is 29%, with a median time to recurrence of 18 months. High-grade tumor was found in 95% of the recurrences, 60% were recurrence free after TURB and BCG, and 11% progressed to T2 disease. Therefore must of the recurrences are able to be treated conservatively, special attention must be paid in T1HG and prostatic urethral recurrences and may prefer a more aggressive approach in this cases.

Dr. Kassouf also highlighted some TMT limitations that don´t apply to elderly patients, such as secondary malignancies, the fact that most series have a follow-up time less than 10 years, and neobladder not advocated following salvage cystectomy, and those are due to the lower life expectancy in this group of patients and the lower renal function in elderly. Yet some questions remain unsolved, as if should pelvic nodes be included in the radiation field or if neoadjuvant chemotherapy prior TMT improves survival, and new trials have to be designed to solve these matters.

Finally, Kassouf concluded his talk by stating that radical cystectomy can be morbid, especially in elderly, the chronological age should not be used to exclude patients from definitive therapy, bladder preservation using TMT is a good option in selected patients and remains underutilized and NAC needs further evaluation in octogenarians.   

Presented by: Wassim Kassouf, MD Medical Advisory and Research Board, McGill University, Montreal, QC

Written by: Ashmar Gómez Conzatti, MD, Urology Resident, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City and Ashish M. Kamat, MD, Professor of Urologic Oncology, MD Anderson Cancer Center, Houston, TX at the 2018 Congreso de la Asociación Mexicana de Urología Oncológica – July 25-28, 2018, Acapulco, GRO México;