Preoperative Immunohistochemical Biomarker Panel Predicts Upstaging at Radical Cystectomy: A Prospective Study
Shahrokh F Shariat, Brian D Robinson, Cathleen E Matrai, Aditya Bagrodia, Varun Rachakonda, Evanguelos Xylinas, Payal Kapur, Arthur I Sagalowsky, Yair Lotan. Weill Cornell Medical College, New York, NY; UT Southwestern Medical Center, Dallas, TX
Background: Accurate tumor staging is essential for patient counseling and clinical decision making. Current processes for estimating clinical stage are imperfect, and discrepancies between clinical and pathologic stages are common. Retrospective studies found cell-cycle and related proliferative biomarkers can add information to standard pathologic tumor features and help improve prognostic accuracy after radical cystectomy (RC). We prospectively tested whether a panel of biomarkers can identify patients likely to be upstaged at RC and thereby improve current clinical staging.
Design: We performed p53, p27, Ki67, and cyclin E1 immunohistochemistry on transurethral resection of the bladder (TURB) specimens from 107 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorized as favorable (<2 altered markers) or unfavorable (>2 altered markers). The primary endpoint of the study was tumor upstaging at RC.
Results: Expression of p53, p27, cyclin E1, and Ki-67 were altered in 73 (68%), 36 (34%), 7 (7%), and 86 (80%) patients, respectively. Overall, 2% of patients exhibited unaltered expression, 17% had 1 biomarker altered, 46% had 2 biomarkers altered, 25% had 3 biomarkers altered, and 10% had all 4 biomarkers altered. Clinical stage distribution was as follows: 18% cTa, 6.5% cTis, 38% cT1, 30% cT2, and 7.5% cT3. Fifty-seven patients (53%) were upstaged when T stage was considered alone and 64 (60%) when T and N stage were both considered as upstaging. Patients with unfavorable biomarker score had a higher likelihood of upstaging at RC (71% vs 44% when T stage considered, p=0.006; 79% vs 49% when T and N stage considered, p=0.003), nodal metastases (47% vs 14%, p<.001) and LVI (50% vs 22%, p=0.01). In multivariate analyses that adjusted for the effects of age, gender, clinical stage, concomitant CIS, and time from TURB to RC, unfavorable biomarker score was independently associated with upstaging (HR 1.64, p=0.03 for T stage alone; HR 1.79, p=0.04 for T and N stage).
Conclusions: Assessment of the number of cell-cycle biomarkers in the TURB specimen improves the prediction of upstaging at RC. The combination of biomarkers improves prediction compared to single biomarkers likely due to the more comprehensive biologic profile. Such a biomarker panel may help identify non-muscle invasive UCBs which are clinically understaged and/or muscle invasive UCBs which may benefit from neoadjuvant chemotherapy.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 2:15 PM
Proffered Papers: Section A, Tuesday Afternoon