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1.
Eur Urol ; 78(5): 657-660, 2020 11.
Article in English | MEDLINE | ID: mdl-32943262

ABSTRACT

Active surveillance (AS) is an accepted management strategy for some patients with renal cell carcinoma, but limited tools are available to identify optimal AS candidates. While renal mass biopsy provides diagnostic information, risk stratification based on biopsy is limited. In a retrospective, multi-institutional cohort that underwent renal mass biopsy followed by surgery, we assessed the ability of the cell cycle proliferation (CCP) score from clinical biopsy specimens to predict adverse surgical pathology (ie, grade 3-4, pT stage ≥3, metastasis at surgery, or papillary type II). Of 202 patients, 98 (49%) had adverse surgical pathology. When added to a baseline model including age, sex, race, lesion size, biopsy grade, and histology, CCP score was significantly associated with adverse pathology when modeled as a binary (odds ratio [OR]: 2.44 for CCP score >0, p = 0.02) and a continuous (OR: 1.72 per one unit increase, p = 0.04) variable. Discriminative performance measured by the area under the curve (AUC) improved from 0.73 in the baseline model to 0.75 and 0.76 in models including the CCP score. In the subgroup of patients with nephrectomy CCP score available (n = 67), the biopsy-based model outperformed the nephrectomy-based model (AUC 0.78 vs 0.75). These data support prospective assessment of biopsy CCP score to confirm clinical validity and assess potential utility in AS-eligible patients. PATIENT SUMMARY: In patients with localized renal cell carcinoma who underwent renal mass biopsy followed by surgery, the cell cycle proliferation score from clinical biopsy specimens could predict adverse surgical pathology.


Subject(s)
Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Nephrectomy , Aged , Biopsy , Cell Cycle , Cell Proliferation , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Treatment Outcome
2.
Eur Urol ; 73(5): 763-769, 2018 05.
Article in English | MEDLINE | ID: mdl-29249291

ABSTRACT

BACKGROUND: There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery. OBJECTIVE: To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC. DESIGN, SETTING, AND PARTICIPANTS: The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed. RESULTS AND LIMITATIONS: A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07-2.09) and DSM (HR 2.49, 95% CI 1.53-4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n=338) and high-risk (n=202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p<0.001). CONCLUSIONS: The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management. PATIENT SUMMARY: In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions.


Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Cell Proliferation/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Transcriptome/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/surgery , Cohort Studies , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/diagnosis , Kidney Neoplasms/surgery , Male , Middle Aged , Multifactorial Inheritance , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/surgery , Nephrectomy/methods , Nephrectomy/mortality , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Retrospective Studies , Statistics, Nonparametric , Survival Analysis , Time Factors , United States
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