Dataset Information

Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy.

ABSTRACT:

Purpose

The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making.

Patients and methods

GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis.

Results

The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (? 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01).

Conclusion

In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.

SUBMITTER: Den RB

PROVIDER: S-EPMC4884273 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy.

Den Robert B RB Yousefi Kasra K Trabulsi Edouard J EJ Abdollah Firas F Choeurng Voleak V Feng Felix Y FY Dicker Adam P AP Lallas Costas D CD Gomella Leonard G LG Davicioni Elai E Karnes R Jeffrey RJ

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20150209 8

<h4>Purpose</h4>The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making.<h4>Patients and methods</h4>GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic be ...[more]

PMID: 25667284

Similar Datasets

Project description:ImportanceActive surveillance is recommended for patients with very low-risk (VLR) and low-risk (LR) prostate cancer. Despite controversy, recent clinical guidelines state surveillance may be considered for men with low-volume intermediate-risk (LVIR) disease.ObjectiveTo compare rates of adverse pathologic findings among VLR, LR, and LVIR men electing immediate radical prostatectomy and evaluate criteria to define if a favorable intermediate-risk group minimizing risk exists.Design, setting, and participantsThis was a cohort study of men (2005-July 2016) with clinically localized VLR (1264 patients), LR (4849 patients), and LVIR (608 patients) (1-2 cores, Gleason 3 + 4 = 7, prostate-specific antigen [PSA] level <20 ng/mL) prostate cancer undergoing radical prostatectomy evaluated retrospectively at Johns Hopkins Hospital.InterventionsRadical prostatectomy.Main outcomes and measuresThe proportions of men found to have at least Gleason 4 + 3 = 7 disease and other adverse pathologic features were compared by risk group. Log-binomial regression calculated relative risk (RR) of adverse pathologic findings in the LVIR cohort compared with VLR and LR cohorts. Analyses were repeated in subgroups of the LVIR population who otherwise met criteria for VLR (T1c, PSA density [PSAD] <0.15 ng/mL/cm3, ≤50% cancer in any core) and LR (≤T2a, PSA level <10 ng/mL) disease. Rates of adverse pathologic findings within the LVIR group were calculated based on various clinical thresholds, and univariable and multivariable logistic regression analyses were performed to identify predictors of adverse pathologic findings.ResultsThe rate of adverse pathologic findings was significantly higher for LVIR disease (150 of 608 patients [24.7%]; RR, 4.50; 95% CI, 3.73-5.43; P < .001) compared with LR disease (280 of 4849 [5.8%]), and LVIR disease (RR, 5.14; 95% CI, 3.84-6.89; P < .001) compared with men with VLR disease (60 of 1264 [4.7%]). Restriction of LVIR men to additional criteria did not significantly affect results. There were no preoperative clinical or pathologic criteria that could identify a subgroup of the LVIR population with rates of adverse pathologic findings comparable with those of the VLR and LR cohorts. PSAD was a significant predictor of adverse pathologic findings, but Gleason score had the largest effect (odds ratio, 4.30 (95% CI, 3.40-5.44; P < .001).Conclusions and relevanceNearly 25% of men (150 of 608) electing immediate radical prostatectomy with low-volume, Gleason 3 + 4 prostate cancer on biopsy are found to harbor adverse surgical pathologic findings. These data do not support the presence of a "favorable" subgroup among included patients and could have important implications for active surveillance in similar patients with Gleason 3 + 4 = 7 prostate cancer.

Project description:Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence). Methods: We constructed a health state transition (Markov) model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer-specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE) (58.3 months) as compared with adjuvant radiotherapy (53.7 months), a difference of 4.6 months (standard deviation 8.8). Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months). Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized management.

Project description:Accurate estimation of recurrence risk is needed for optimal treatment of clinically localized prostate cancer (PCa) patients. We combined classical clinicopathological predictors of biochemical recurrence (BCR) and molecular markers into a new risk score for predicting BCR after radical prostatectomy (RP). A retrospective study which included 122 PCa patients who attended our department between 2000 and 2007 was conducted. Total RNA was isolated from formalin-fixed paraffin embedded PCa tissue. Gene expression patterns were analyzed in 21 selected samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in an independent retrospective series of 101 patients with ≥ 10 years follow-up who underwent RP for clinically localized PCa. Univariate and multivariate logistic regression analysis were used to identify individual predictors of BCR. A risk score (RS) for predicting BCR including clinicopathological and gene expression data was developed and Kaplan-Meier curves were generated. Interaction networks between the genes of the model were built by GeneMANIA Cytoscape plugin. In a median follow-up of 120 months (range 3-190), 37 patients developed BCR (36.6%). Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR<0.1). A set of 41 genes were validated by quantitative PCR. Regression analysis showed that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion and positive margins were independent prognostic factors of BCR. A RS generated using these gene expression and clinicopathological variables was able to discriminate between two groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, p<0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the two genes of the model were not found. In conclusion, identification of new gene expression patterns associated with a high probability of BCR in clinically localized PCa patients treated with RP, and their combination with clinicopathological variables in a robust, easy-to-use and reliable classifier may contribute to improve PCa risk stratification and, consequently, to tailor treatment and surveillance strategies in these patients.

Project description:OBJECTIVE:To evaluate the performance of the Decipher test in predicting lymph node invasion (LNI) on radical prostatectomy (RP) specimens. METHODS:We identified 1,987 consecutive patients with RP who received the Decipher test between February and August 2015 (contemporary cohort). In the contemporary cohort, only the Decipher score from RP specimens was available for analysis. In addition, we identified a consecutive cohort of patients treated with RP between 2006 and 2012 at the University of California, San Diego, with LNI upon pathologic examination (retrospective cohort). The retrospective cohort yielded seven, 22, and 18 tissue specimens from prostate biopsy, RP, and lymph nodes (LNs) for individual patients, respectively. Univariable and multivariable logistic regression analyses were used to evaluate the performance of Decipher in the contemporary cohort with LNI as the endpoint. In the retrospective cohort, concordance of risk groups was assessed using validated cut-points for low (<0.45), intermediate (0.45-0.60), and high (>0.60) Decipher scores. RESULTS:In the contemporary cohort, 51 (2.6%) patients had LNI. Decipher had an odds ratio of 1.73 (95% confidence interval, 1.46-2.05) and 1.42 (95% confidence interval, 1.19-1.7) per 10% increase in score on univariable and multivariable (adjusting for pathologic Gleason score, extraprostatic extension, and seminal vesicle invasion), respectively. No significant difference in the clinical and pathologic characteristics between the LN positive patients of contemporary and retrospective cohorts was observed (all P>0.05). Accordingly, among LN-positive patients in the contemporary cohort and retrospective cohort, 80% and 77% had Decipher high risk scores (P=1). In the retrospective cohort, prostate biopsy cores with the highest Gleason grade and percentage of tumor involvement had 86% Decipher risk concordance with both RP and LN specimens. CONCLUSION:Decipher scores were highly concordant between pre- and post-surgical specimens. Further, Decipher scores from RP tissue were predictive of LNI at RP. If validated in a larger cohort of prostate biopsy specimens for prediction of adverse pathology at RP, Decipher may be useful for improved pre-operative staging.

Dataset Information

Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy.

Purpose

Patients and methods

Results

Conclusion

Publications

Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets