Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer

Abstract

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

Use and early mortality outcomes of active surveillance in patients with intermediate‐risk prostate cancer

“…[29][30][31] The data from the current study also demonstrated a larger difference in OS compared with PCSM among these populations. Therefore, the current study data affirm NCCN guidelines indicating that caution should be applied when considering AS for men with favorable intermediate-risk disease as we await longer follow-up data regarding population-wide outcomes with AS.…”

Age dependence of modern clinical risk groups for localized prostate cancer—A population‐based study

“…The overall pattern of greater proportions of regional and metastatic PCa in the elderly is an expected finding, at least in part: older men are less likely to be screened for PCa than their younger counterparts and are more likely to undergo PSA testing because of urinary symptoms. However, older men may also be more likely to present with metastatic disease because they are already at increased risk of having an undetected potentially lethal cancer, and this makes them more prone to metastases . Detecting these cancers at an earlier stage may have permitted curative therapy and the avoidance of metastatic spread.…”

“…The ASIRs shown here indicate that the absolute incidence of potentially lethal disease actually increases in men older than 70 years. The 10‐year metastasis rates for men with unfavorable intermediate‐risk disease and high‐risk disease are quite high . Men aged 70 to 75 years typically have estimated life expectancies longer than 10 years, and healthy men up to the age of 80 years can have life expectancies exceeding 10 years .…”

“…Modern risk stratification includes an important distinction between unfavorable and favorable intermediate‐risk cancer . Unfavorable intermediate‐risk disease and high‐risk disease have similar rates of developing distant metastases and PCa‐specific mortality . This differentiation has been incorporated into clinical management and the eighth edition of the American Joint Committee on Cancer staging guidelines for PCa .…”

“…This differentiation has been incorporated into clinical management and the eighth edition of the American Joint Committee on Cancer staging guidelines for PCa . The difference between Gleason 4 + 3 disease and Gleason 3 + 4 disease is also included in these guidelines . However, age associations have not been reported for these modern groupings.…”