Chemotherapy 'Vastly Underutilized' in Bladder Cancer

Yael Waknine

April 16, 2014

A major weapon in the armamentarium against bladder cancer — neoadjuvant chemotherapy (NACT) — is rarely used in clinical practice, according to a large population study published online April 14 in Cancer.

Researchers analyzed 2944 patient records from the Ontario Cancer Registry, and found that a mere 4% of patients, on average, received standard-of-care NACT prior to cystectomy for muscle-invasive bladder cancer from 1994 to 2008.

Surprisingly, the popularity of adjuvant chemotherapy (ACT) rose over the same period; it was 16% from 1994 to 1998, 18% from 1999 to 2003, and 22% from 2004 to 2008.

Moreover, the controversial ACT was linked to benefits deemed "probably on the same order of magnitude" as NACT (all-cause mortality hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62 - 0.81; cancer-related HR, 0.73; 95% CI, 0.64 - 0.84), after relevant patient- and disease-related characteristics were controlled for.

"Patients having surgery for bladder cancer should have chemotherapy, either before or after surgery. Efforts are needed to improve uptake of this treatment, which appears to be vastly underutilized," lead researcher Christopher Booth, MD, FRCPC, division of cancer care and epidemiology at the Queen's University Cancer Research Institute in Kingston, Ontario, Canada, said in a statement. The answer, however, might not be that simple.

"This problem is not unique to Ontario, and has been identified by researchers in the United States and Europe. It likely relates to a complex interaction between physician knowledge, beliefs, attitudes, and patient preferences," Dr. Booth told Medscape Medical News in an interview.

In fact, NACT has not lived up to the 5-year overall survival rates heralded by previous clinical trials of 57% (N Engl J Med. 2003;349:859-866) and 49% (J Clin Oncol. 2011;29:2171-2177).

The Ontario data showed only a modest benefit with NACT (25%; 95% CI, 17% - 34%). The researchers attribute this to selection and referral biases, differences in surgical technique, and the association between greater cystectomy case volumes and improved outcomes. Cancer-specific survival was 28% (95% CI, 24% - 33%).

Then again, in "real life," NACT was more common in patients with poorer prognoses related to T3/T4 tumors (odds ratio [OR], 1.83; 95% CI, 1.38 - 2.46), node-positive disease (OR, 8.10; 95% CI, 6.2 - 10.7), and lymphovascular invasion (OR, 1.53; 95% CI, 1.11 - 2.15). Younger patients and those in hospitals affiliated with a regional cancer center were more likely to be offered NACT (OR,1.73; 95% CI, 1.18 - 2.55) and ACT (OR,1.43; 95% CI, 1.12 - 1.83).

"This issue is a perfect example of the disconnect between the efficacy of an intervention as studied in the context of a clinical trial, and its efficacy when applied to real-world patients," Matthew Galsky, MD, told Medscape Medical News. The increased use of ACT suggests that cisplatin ineligibility due to renal impairment is only part of the problem, he added.

Dr. Galsky, who was not involved in the study, is associate professor of medicine and director of genitourinary medical oncology at the Icahn School of Medicine, Tisch Cancer Institute at Mount Sinai, in New York City.

"Another suspected major issue is that despite level I evidence supporting [NACT], a large number of clinicians don't believe the data, feel that the studies were flawed, feel that the benefit is modest, or feel that they can select patients who will do fine with surgery alone," he explained.

"If these perceptions exist and patients are not referred to a medical oncologist to discuss the risks and benefits of [NACT] prior to surgery, then clearly [NACT] will not be used. The higher uptake of adjuvant chemotherapy, where the operation is already done and risk stratification can be based on more precise pathologic staging, hints that this is likely occurring in practice," Dr. Galsky added.

"Ultimately, studies are needed to prospectively determine the reasons [NACT] is not being administered — instead of just speculating. Such studies are now being done by the Bladder Cancer Advocacy Network and other groups, and will shed light on this issue. In parallel with understanding why the current standards of care are not being utilized, we clearly also need much better tolerated and much more effective treatments. I imagine that the availability of such interventions would progressively narrow the gap between efficacy and effectiveness," Dr. Galsky concluded.

The study was funded by Cancer Care Ontario; the Canadian Foundation for Innovation; and the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Booth and Dr. Galsky report have disclosed no relevant financial relationships.

Cancer. Published online April 14, 2014. Abstract


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