Data Support Safety and Benefit of Chemotherapy Before Radical Cystectomy

David Johnson, MD

Preoperative chemotherapy was not a predictor of postoperative complications, nor did it increase the length of hospital stays or surgical complications among patients undergoing radical cystectomy for muscle-invasive bladder cancer.

Yet the use of platinum-based multiagent neoadjuvant chemotherapy (NAC) in radical cystectomy patients was “strikingly low” in a retrospective analysis of data from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP).*¹ These data mirror results from other studies detailing underuse of a safe, guidelines-recommended treatment strategy that is also associated with a survival advantage.^2-5

David Johnson, MD, reported these findings on behalf of a group of researchers from the University of North Carolina, Chapel Hill during the Annual Meeting of the Southeastern Section of the American Urological Association.

The ACS-NSQIP Participant Use Data File spans the years 2005-2011 and includes data on 135 variables, including perioperative information, 30-day postoperative complications, and mortality at the contributing institutions. During that time period, in this analysis of 878 patients who underwent radical cystectomy, a total of 457 patients (52%) experienced at least one complication within 30 days after surgery, Johnson et al reported.

The investigators found that NAC did not significantly increase the morbidity associated with radical cystectomy. Their analysis revealed no significant differences in postoperative complication rates and no increase in operative time associated with the use of NAC. Further, NAC was a significant predictor of shorter length of hospital stay by multivariate analysis, when adjusting for significant predictors of length of stay such as age, race, year of operation, functional status, and operative time (P=.02).

“Our study basically takes a large dataset that includes both academic and community hospitals and looks at a nationwide picture of utilization of neoadjuvant chemotherapy. What it shows is that the utilization rate is still quite low even though there is an unequivocal survival benefit,” Johnson said. In a meta-analysis and a later update of that study that included 3005 patients from 11 randomized trials, NAC demonstrated an approximately 5% increase in 5-year overall survival.^3,4

Only 8.9% of patients who underwent radical cystectomy from 2005 to 2011 and were included in the Johnson et al study received NAC. This low NAC use rate was not explained by excluding patients for whom treatment with chemotherapy would be a health risk: only seven patients had preoperative renal failure, a potential contraindication, Johnson explained.

“We know that we have not been able to affect survival just by improvements in surgical techniques and detection and diagnostic techniques,” he said. “That leads us to believe that we need something more to treat it as a systemic disease. The problem is that it has not been widely implemented.”

Why is this? Two recent reviews of data on the underuse of chemotherapy in the setting of bladder cancer concluded that the utilization of neoadjuvant chemotherapy is attributable to the choice of patients and/or physicians based on factors that can include advanced patient age, patient comorbidities such as renal and/or cardiac dysfunction, and a perception of limited benefit.^6,7

Figure. Bivariable Analysis: Overall Complications: 457/878 (52%)

NAC indicates neoadjuvant chemotherapy.

In some instances, patients and physicians may not want to delay surgery. Or, they are uncomfortable about the potential toxicities of neoadjuvant chemotherapy. (There is a high overall complication rate with chemotherapy, although it is higher with adjuvant than with neoadjuvant administration.)

Some patients, Johnson said, may think that “a 5% survival benefit is not worth going through 3 months of chemotherapy.” Or, physicians/ surgeons may demur because they are not familiar with or do not believe the data, or they themselves do not think the 5% survival benefit is worth putting the patient through the chemotherapy.

Experience with the regimen and a multidisciplinary team setting may contribute to greater use of neoadjuvant therapy in bladder cancer. At the University of North Carolina, as with other high-volume cancer centers, Johnson said, treatment decisions are made within multidisciplinary clinics where the patient is a team member.

“That is what we do at UNC to promote appropriate use of neoadjuvant chemotherapy,” he said, “and it may be one of the best ways of doing it.”

*The ACS NSQIP and the hospitals participating in the ACS NSQIP are the source of the data used herein. They have not been verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.

References

1. Johnson D, Kirby W, Ferguson J, et al. Utilization of preoperative chemotherapy and associated outcomes after radical cystectomy: an analysis of the American College of Surgeons National Quality Improvement Program. Presented at: the 77th Annual Meeting of the Southeastern Section, American Urological Association (SESAUA); March 14-17, 2013; Williamsburg, VA. Abstract 53.
2. National Comprehensive Cancer Network. NCCN Guidelines and Compendium Update: Bladder Cancer. http://www.nccn.org/about/news/ebulletin/2012-11-26/guidelines_compendium.asp. Accessed April 29, 2013.
3. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer Meta-Analysis Collaboration. Lancet. 2003;361(9373):1927-1934.
4. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer Meta-Analysis Collaboration. Eur Urol. 2005;48(2):202-205. Published online ahead of print, April 21, 2005.
5. Winquist E, Kirchner TS, Segal R, Chin J, Lukka H. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol. 2004;171(2 Pt 1):561-569.
6. Meeks JJ, Bellmunt J, Bochner BH, et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2012;62(3):523-533. Published online ahead of print, June 1, 2012.
7. Sternberg CN, Bellmunt J, Sonpavde G, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol. 2013;63(1):58-66. Published online ahead of print, August 14, 2012.