Purpose The purpose of this guideline is to provide a clinical framework for follow-up of clinically localized renal neoplasms undergoing active surveillance, or following definitive therapy. ...Materials and Methods A systematic literature review identified published articles in the English literature between January 1999 and 2011 relevant to key questions specified by the Panel related to kidney neoplasms and their follow-up (imaging, renal function, markers, biopsy, prognosis). Study designs consisting of clinical trials (randomized or not), observational studies (cohort, case-control, case series) and systematic reviews were included. Results Guideline statements provided guidance for ongoing evaluation of renal function, usefulness of renal biopsy, timing/type of radiographic imaging and formulation of future research initiatives. A lack of studies precluded risk stratification beyond tumor staging; therefore, for the purposes of postoperative surveillance guidelines, patients with localized renal cancers were grouped into strata of low- and moderate- to high-risk for disease recurrence based on pathological tumor stage. Conclusions Evaluation for patients on active surveillance and following definitive therapy for renal neoplasms should include physical examination, renal function, serum studies and imaging and should be tailored according to recurrence risk, comorbidities and monitoring for treatment sequelae. Expert opinion determined a judicious course of monitoring/surveillance that may change in intensity as surgical/ablative therapies evolve, renal biopsy accuracy improves and more long-term follow-up data are collected. The beneficial impact of careful follow-up will also need critical evaluation as further study is completed.
•PI-RADS and cell cycle risk scores are only modestly correlated.•The cell cycle progression score predicted tumor grade better than PI-RADS.•Molecular information is essential for accurate prostate ...cancer risk assessment.
To compare the prognostic capabilities and clinical utility of the cell cycle progression (CCP) gene expression classifier test, multiparametric magnetic resonance imaging (mpMRI) with Prostate Imaging Reporting and Data System (PI-RADS) scoring, and clinicopathologic data in select prostate cancer (PCa) medical management scenarios.
Retrospective, observational analysis of patients (N = 222) ascertained sequentially from a single urology practice from January 2015 to June 2018. Men were included if they had localized PCa, a CCP score, and an mpMRI PI-RADS v2 score. Cohort 1 (n = 156): men with newly diagnosed PCa, with or without a previous negative biopsy. Cohort 2 (n = 66): men who initiated active surveillance (AS) without CCP testing, but who received the test during AS. CCP was combined with the UCSF Cancer of the Prostate Risk Assessment (CAPRA) score to produce a clinical cell-cycle risk (CCR) score, which was reported in the context of a validated AS threshold. Spearman's rank correlation test was used to evaluate correlations between variables. Generalized linear models were used to predict binary Gleason score category and medical management selection (AS or curative therapy). Likelihood-ratio tests were used to determine predictor significance in both univariable and multivariable models.
In the combined cohorts, modest but significant correlations were observed between PI-RADS score and CCP (rs = 0.22, P = 8.1 × 10−4), CAPRA (rs= 0.36, P = 4.8 × 10−8), or CCR (rs = 0.37, P = 2.0 × 10−8), suggesting that much of the prognostic information captured by these measures is independent. When accounting for CAPRA and PI-RADS score, CCP was a significant predictor of higher-grade tumor after radical prostatectomy, with the resected tumor approximately 4 times more likely to harbor Gleason ≥4+3 per 1-unit increase in CCP in Cohort 1 (Odds Ratio OR, 4.10 95% confidence interval CI, 1.46, 14.12, P = 0.006) and in the combined cohorts (OR, 3.72 95% CI, 1.39, 11.88, P = 0.008). On multivariable analysis, PI-RADS score was not a significant predictor of post-radical prostatectomy Gleason score. Both CCP and CCR were significant and independent predictors of AS versus curative therapy in Cohort 1 on multivariable analysis, with each 1-unit increase in score corresponding to an approximately 2-fold greater likelihood of selecting curative therapy (CCP OR, 2.08 95% CI, 1.16, 3.94, P = 0.014) (CCR OR, 2.33 95% CI, 1.48, 3.87, P = 1.5 × 10−4). CCR at or below the AS threshold significantly reduced the probability of selecting curative therapy over AS (OR, 0.28 95% CI, 0.13, 0.57, P = 4.4 × 10−4), further validating the clinical utility of the AS threshold.
CCP was a better predictor of both tumor grade and subsequent patient management than was PI-RADS. Even in the context of targeted biopsy, molecular information remains essential to ensure precise risk assessment for men with newly diagnosed PCa.
Accurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression ...(CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer.
The pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables.
The CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10
after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10
). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%).
Both CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.
The combined clinical cell-cycle risk (CCR) score is a validated model that combines the cell-cycle progression (CCP) score with the University of California San Francisco Cancer of the Prostate Risk ...Assessment (CAPRA) score. This score determines the risk of progressive disease for men with prostate cancer. Here, we further validate the prognostic ability of the CCR score and evaluate its ability to help determine which patients may safely forgo multimodality therapy.
We evaluated the CCR and a CCR-based multimodality threshold (2.112) in a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Network intermediate- or high-risk localized disease (N = 718). These men received single or multimodality therapy (androgen deprivation with radiation RT, or surgery with adjuvant RT or hormones).
CCR score prognosticated metastasis for single-modality therapy, as a continuous variable (hazard ratio, 3.97; 95% confidence interval CI, 2.61-6.06) and when dichotomized at the threshold (hazard ratio, 15.90; 95% CI, 5.43-46.52). The 10-year Kaplan-Meier risk for those receiving single-modality (RT or surgical) therapy with CCR scores below and above the threshold for single-modality treatment was 4.3% (95% CI, 1.0%-17.1%) and 20.4% (95% CI, 13.2%-30.7%), respectively. Using the threshold, 27% of men with newly diagnosed high-risk and 73% with unfavorable intermediate-risk disease could avoid multimodality therapy.
Patients with CCR scores below the multimodality threshold (2.112) may safely forgo multimodality therapy. The CCR score can be used as a decision aid to counsel men whether or not single-modality therapy would be sufficient for their intermediate- or high-risk prostate cancer.
•A CCR score prognosticated metastasis better than risk group.•A score threshold determines who can be safely treated with a single modality.•The score can determine the absolute benefit of multimodality therapy.
Using a retrospective, multi-institutional cohort of men with prostate cancer (N = 718), this study evaluated a score that combines a genome expression classifier and clinical information to prognosticate progression to metastatic disease in various treatment contexts. A score threshold identified men with intermediate- and high-risk prostate cancer who could safely forgo multimodal therapy.
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