Half of Biopsies for Bladder Cancer Inadequate for Staging

Veronica Hackethal, MD

October 24, 2014

Almost half of biopsy specimens for bladder cancer may be inadequate for proper staging, and low-quality biopsies are associated with higher mortality, according to a study by UCLA researchers published online October 22 in Cancer.

"This study demonstrates that many patients with bladder cancer are getting inadequate bladder biopsies and are likely being treated in a way that may not reflect their true stage," commented Karim Chamie, MD, assistant professor of urology and surgical director of the bladder cancer program at UCLA.

Inadequate bladder biopsies, in which there is no bladder wall muscle in the specimen, are associated with worse outcomes, Dr Chamie added. Although cancer staging is often considered the most important predictor of life expectancy, as well as an important determinant of treatment, staging is significantly less likely to be accurate with an inadequate biopsy, Dr Chamie explained.

A possible reason could be that physicians may perceive that deep biopsies could violate tenets of the Hippocratic Oath to "first do no harm," according to Dr Chamie.

"Urologists oftentimes don't want to take deep biopsies because they don't want to perforate or rupture the bladder," Dr Chamie told Medscape Medical News. "Deeper biopsies may also be associated with more pain or bleeding."

Inadequate staging, however, may actually place patients at risk for much greater harm by creating the belief that that the cancer is less aggressive than it truly is, Dr Chamie continued. Urologists may be unable to predict which patients should undergo deep biopsies at the time of diagnosis. Moreover, the aggressiveness of the tumor needs to be determined through microscopic examination by a pathologist.

"We must turn to our colleagues in pathology and societal organizations to help integrate the quality of the biopsy in the staging of the cancer," Dr Chamie asserted.

Using data from the Los Angeles National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, researchers reviewed medical records and operative reports for patients across Los Angeles County who had been diagnosed with noninvasive bladder cancer from 2004 to 2005. They also looked to see whether pathology reports mentioned the presence or absence of muscle. Then they looked at associations between biopsy quality and survival.

The study did not include information on comorbid conditions and tobacco use. Additionally, researchers did not have access to pathology slides for review, which could have limited the study.

The analysis included 1865 patients with a median age of 73 years. The majority were male (73%) and white (69.8%). Researchers reviewed records written by 335 urologists and 278 pathologists. About 52% of initial pathology reports mentioned muscle as present; 30% mentioned muscle as absent; and almost 18% did not mention muscle at all.

Compared with those with adequately staged cancer, those whose biopsy specimens did not contain muscle or whose reports did not mention muscle had significantly increased risk for death from bladder cancer (HR, 1.48 [95% CI, 1.00 - 2.18]; and HR, 1.91 [95% CI, 1.12 - 3.24], respectively). Patients with high-grade disease had higher 5-year cancer-specific mortality when muscle was absent or not mentioned: 8% (present), 13% (absent), and 21.5% (not mentioned).

Patients who were women (P < .01), black or of other race (P = .03), unmarried (P = .01), of lower socioeconomic status (P < .01), or had lower-stage or lower-grade cancers (for both, P < .01) and who received treatment at a non–National Cancer Institute–designated cancer center (P < .01) had significantly worse-quality biopsies (absence of muscle).

Researchers found significantly better-quality biopsies among men (OR, 1.41; 95% CI, 1.05 - 1.89) and those of advanced age (aged 66 to 75 years: OR, 1.60; 95% CI, 1.02 - 2.50; 76 - 85 years: OR, 1.59; 95% CI, 1.03 - 2.47).

Dr Chamie and colleagues proposed a new staging scheme that would indicate inadequate biopsies, perhaps with an "x," as in "stage Ix," to alert patients and physicians about poor-quality biopsies and that a repeat biopsy may be necessary.

"Over the last two decades, new chemotherapies and innovations have been introduced and integrated in the delivery of care for patients with bladder cancer. However, we have yet to see significant improvements in outcomes for patients with bladder cancer," Dr Chamie commented. "I think this in part may be attributed to misclassification and mis-staging. When we don't perform an adequate biopsy, we may be placing our patients at an unwarranted disadvantage."

The authors report no relevant financial relationships.

Cancer. Published online October 22, 2014. Abstract

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