PerspectiveIn the Journals

Inadequate bladder cancer biopsy linked to increased mortality

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November 4, 2014

The absence of muscle in the specimen in nearly 50% of all diagnostic resections for bladder cancer was linked to increased mortality, particularly among patients with high-grade disease.

These findings suggest inadequate cancer staging by either the urologist or the pathologist, the researchers wrote.

“These findings are very important because while patients know about the stage of their cancer, they rarely question the quality of the biopsy,” researcher Karim Chamie, MD, assistant professor of urology at the UCLA Jonsson Comprehensive Cancer Center, said in a press release. “We hope these findings will help empower patients to ask about the quality of their biopsy and, if it is suboptimal, then urge their doctors to repeat the biopsy prior to deciding on what type of treatment to prescribe.”

Karim Chamie

Chamie and colleagues reviewed the Los Angeles SEER registry to identify the records of 1,865 consecutive patients in Los Angeles County diagnosed with nonmuscle-invasive (stage Ta, Tis and T1) urothelial carcinoma of the bladder. The median patient age was 73 years, and the study population was 76.5% male.

Patient medical charts were used to obtain the following information: cancer center where resection was performed, operating urologist, reporting pathologist, quality of staging and TNM staging. The investigators then merged these data with the SEER database to determine patient demographics, tumor characteristics and follow-up information. They stratified staging quality based on the presence, absence or reference to detrusor muscle in the pathology report.

The researchers used chi-square test analysis to correlate the categorical variables with the existence or mention of detrusor muscle. They then used a multivariate model to establish the correlations between staging quality with patient demographics and tumor characteristics.

Researchers determined bladder cancer-related mortality rates through a maximum likelihood, competing-risks regression model. The event of interest was defined as bladder cancer-related death, whereas the competing event was noncancer-related death. The model adjusted for several demographic variables. The estimates were expressed as sub-hazard ratios with 95% CIs.

The researchers found that in the initial pathology reports, muscle was reported as present in 972 (52.1%) of the specimens, as absent in 564 (30.2%) of the specimens and not mentioned in 329 (17.7%) cases. The grade or depth of cancer invasion did not appear to affect the presence of muscle in the specimens.

Staging quality was correlated with mortality (P<.05). The 5-year cancer-specific mortality among patients with high-grade disease was as follows; 8% when muscle was present in the specimen, 13% when muscle was absent and 21.5% when muscle was not mentioned in the report.

“Appropriately staging patients with bladder cancer is a skill set that every urologist and pathologist should have in his/her armamentarium,” Chamie said. “Not all stage I cancers are alike. Some patients may have stage II cancer, but because the biopsy was insufficient, these patients were inaccurately staged and may be undertreated. I really do believe that one reason why we have yet to see significant improvement in bladder cancer survival over the last 2 decades may, in part, be attributed to inadequate staging.”

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
Petros Grivas

Petros Grivas

Chamie and colleagues analyzed SEER registry-derived data from 1,865 patients and provided evidence at a population level on the critical role and importance of adequate staging of bladder cancer. In this study, the absence of muscle layer (muscularis propria) in the bio-specimen or its frequent omission in the pathology report was associated with higher mortality, especially in high-grade disease. There has been data regarding the frequent absence of muscularis propria in transurethral resection of bladder tumor (TURBT) specimens that may result in under-staging and, thus, inappropriate treatment. Moreover, even very experienced pathologists often may have difficulty differentiating between “muscularis mucosae” and “muscularis propria” in inadequate specimens. Inter- and intra-observer variability also is well described.
In case of inadequate presence of muscularis propria (or high suspicion of muscle layer invasion without such definitive evidence), it is critical to repeat TURBT to ensure adequate presence of muscularis propria to aid the pathologist to report accurate staging. Ta, Tis and T1 stages (non-muscle invasive) have different management and prognosis compared with T2 (muscle-invasive) stage. For example, in the latter case, the risk of micro-metastasis is much higher, and discussion about the role of neoadjuvant cisplatin-based chemotherapy — as well as evaluation of patient candidacy for such therapy — is recommended. However, it is not uncommon to discuss particular cases without definitive muscle invasion but high index of suspicion in inter-disciplinary tumor boards for consensus about management. The risk of under-staging is certainly lower but still present even in the presence of muscularis propria (especially if limited presence). Therefore, diligent review of clinical, radiological and pathologic information is important for evidence-based decision-making in these patients. Communication between urology and pathology and quality control are very important to ensure the presence of muscle layer in TURBT specimens and appropriate mention of its presence/absence in the pathology report.

Petros Grivas, MD, PhD
Taussig Cancer Institute, Cleveland Clinic

Disclosure: Grivas reports no relevant financial disclosures.