Friday, November 7, 2014

Bladder Preservation Strategies in the Treatment of Muscle-Invasive Bladder Cancer

It is estimated that in 2014, there will be 74,690 new cases bladder cancer and 15,580 deaths secondary to bladder cancer.1 Approximately 20-30% of patients with bladder cancer present with muscle-invasive bladder cancer (MIBC). The standard of care for MIBC is a radical cystectomy with removal of the pelvic lymph nodes, with some patients undergoing chemotherapy prior to surgery (neoadjuvant chemotherapy). While radical cystectomy is the preferred treatment option, it has significant morbidity and implications on quality of life.2,3 Therefore, bladder preservation therapies for MIBC have been developed, and may be an option for a select group of patients.4

Bladder preservation strategies include combination therapies as well as single modality therapies. Trimodal therapy, consisting of an aggressive transurethral resection of bladder tumor followed by concurrent chemotherapy and radiation therapy, is the most strongly supported and accepted bladder preservation option. In a recent systematic review, the 5-year cancer specific survival in medically operable patients undergoing trimodal therapy was 50-82%.5 These numbers are comparable to large radical cystectomy series. While there are no randomized trials comparing trimodal therapy to radical cystectomy, there is a growing body of accumulated data suggesting that trimodal therapy is a reasonable treatment option in well-selected patients.

While trimodal therapy is the most accepted option for bladder preservation, for the remainder of this post, we will discuss the role of each individual modality (transurethral resection, chemotherapy, and radiotherapy) in trimodal therapy, and outline some non-traditional approaches to bladder preservation.

Transurethral resection of bladder tumor

Transurethral monotherapy involves excising all visible tumor with deep resection. In highly selected patients, Dr. Harry Herr presented a series of 151 patients with MIBC that underwent an aggressive transurethral resection of bladder tumor with 10 years of follow-up.6 Of these patients, 99 underwent transurethral resection alone and 52 underwent radical cystectomy. There was no significant difference in survival between these groups, and overall, 57% of patients in this study survived more than 10 years with a functioning bladder. While these results are noteworthy, limited data overall supporting radical transurethral resection as monotherapy. Furthermore, there is a lifelong risk of developing recurrent invasive tumor in retained bladder: 42% of patients in this study underwent salvage radical cystectomy. The general consensus is that transurethral resection alone provides inadequate cancer control with high rate of recurrence and progression.

Chemotherapy

While the primary role for chemotherapy in the treatment of MIBC is neoadjuvant chemotherapy, there are circumstances where a patient will have no evidence of tumor following chemotherapy, and will subsequently refuse a cystectomy. Small series have described this scenario with good outcomes. In a recent retrospective review of 32 patients with muscle-invasive bladder cancer that had a clinical complete response to neoadjuvant chemotherapy, 25 patients refused to undergo an immediate cystectomy.7 Of the 25 patients that refused immediate cystectomy, 7 patients underwent delayed cystectomy for relapse and 18 patients successfully maintained their bladders. There was no difference in the cancer specific survival between patients that underwent immediate cystectomy and patients that opted for a bladder preservation strategy. We see that in select patients that achieve a complete response to neoadjuvant chemotherapy, bladder preservation may be achieved. However, at this point, it is difficult to determine who will have a response to neoadjuvant chemotherapy, and of those, who will be able to durably maintain their bladders.

Radiation Therapy

A multicentered randomized phase 3 trial examined the role of radiation alone versus radiation with chemotherapy in the treatment of MIBC.8 The authors found that the locoregional and invasive disease free survival was significantly better in the patients that underwent chemoradiation therapy as opposed to radiation alone. Furthermore, there was no increased toxicity with the addition of chemotherapy. The authors did not compare these modalities to patients undergoing cystectomy. Overall, when examining bladder preservation options, there is no role for radiation therapy alone, as concurrent chemoradiation is more effective.

SUMMARY

In conclusion, there are multiple options for bladder preservation. There are large trials reporting outcomes for trimodal therapy and small series for single modality treatments. From these experiences, we see that bladder preservation strategies can lead to acceptable outcomes, and may be considered a reasonable treatment option in select patients. Bladder preservation is not an option for all patients with MIBC, and patient selection is of paramount importance. Furthermore, it is essential to recognize that in these studies, only select patients were included. Bladder preservation is a treatment approach under investigation, and prospective trials comparing trimodal therapy and single modality bladder preservation options to radical cystectomy are needed to better define their role in the treatment of MIBC.



This blog was written by Alexa Meyer, Medical Student at Columbia University College of Physicians & Surgeons in New York, New York.  Alexa recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "Trimodal Therapy for Bladder Cancer" from which this blog is inspired. Alexa is looking forward to a career in urology.






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3. Goodney PP, Stukel TA, Lucas FL, Finlayson EV, Birkmeyer JD. Hospital volume, length of stay, and readmission rates in high-risk surgery. Ann Surg 2003;238:161-7.
4. Smith ZL, Christodouleas JP, Keefe SM, Malkowicz SB, Guzzo TJ. Bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC): a review of the literature and a practical approach to therapy. BJU Int 2013;112:13-25.
5. Ploussard G, Daneshmand S, Efstathiou JA, et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. Eur Urol 2014;66:120-37.
6. Herr HW. Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. J Clin Oncol 2001;19:89-93.
7. Meyer A, Ghandour R, Bergman A, et al. The natural history of clinically complete responders to neoadjuvant chemotherapy for urothelial carcinoma of the bladder. J Urol 2014;192:696-701.
8. James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012;366:1477-88.

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