Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men

Ross, Ashley E.; Johnson, Michael H.; Yousefi, Kasra; Davicioni, Elai; Netto, George J.; Marchionni, Luigi; Fedor, Helen; Glavaris, Stephanie; Choeurng, Voleak; Buerki, Christine; Erho, Nicholas; Lam, Lucia L.C.; Humphreys, Elizabeth B.; Faraj, Sheila F.; Bezerra, Stephania M.; Han, Misop; Partin, Alan W.; Trock, Bruce J.; Schaeffer, Edward M.

doi:10.1016/j.eururo.2015.05.042

Cited by 211 publications

(204 citation statements)

References 39 publications

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“…We present descriptive statistics focused on medians and interquartile ranges (IQRs) or frequencies and percentages as appropriate. Treatment recommendations were analyzed as stratified by Decipher risk categories 22. Exact binomial CIs were constructed to measure changes in treatment recommendations, before and after the Decipher test results.…”

Section: Methodsmentioning

confidence: 99%

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO‐IMPACT study

Gore

Plessis

Santiago-Jiménez

et al. 2017

Cancer

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BACKGROUNDPatients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT.METHODSA total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)‐specific decisional effectiveness and PCa‐related anxiety.RESULTSBefore the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%‐25%) of treatment recommendations changed in the ART arm, including 31% among high‐risk patients; and 32% (95% CI, 24%‐42%) of management recommendations changed in the salvage arm, including 56% among high‐risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before Decipher, 27 and after Decipher, 23 [P<.001]). PCa‐specific anxiety changed after Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa‐specific anxiety in the SRT arm (P = .05) decreased significantly among low‐risk patients. Decipher results reported per 5% increase in 5‐year metastasis probability were associated with the decision to pursue ART (odds ratio, 1.48; 95% CI, 1.19‐1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09‐1.81) in multivariable logistic regression analysis.CONCLUSIONSKnowledge of Decipher test results was associated with treatment decision making and improved decisional effectiveness among men with PCa who were considering ART and SRT. Cancer 2017;123:2850–59. © 2017 American Cancer Society.

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Section: Methodsmentioning

confidence: 99%

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO‐IMPACT study

Gore

Plessis

Santiago-Jiménez

et al. 2017

Cancer

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“…Other gene expression assays have been utilized to examine post-prostatectomy outcomes and have been shown to predict biochemical free, metastasis free and cancer specific survival [14]. For example, Den et alcompared a genome classifier score between salvage and adjuvant radiation patients and its ability to predict clinical metastasis development [6].…”

Section: Discussionmentioning

confidence: 99%

Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence

Koch

Cho

Kaimakliotis

et al. 2016

CBM

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Abstract. BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE: We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy.

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“…Figure S1. On the basis of previously defined CAPRA-S risk categories, 15 6, 58 and 36% of men were classified as low (0-2), intermediate (3)(4)(5) and high risk (6-12), respectively and the cumulative incidence of metastasis at 10 years post RP was 11.3, 3.3 and 21.4%, respectively. In contrast, Decipher score classified 57, 27 and 16% as low (o0.45), intermediate (0.45-0.60) and high risk (40.60), respectively.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 Decipher has been examined in multiple cohorts and post-prostatectomy settings and has been found to be an independent predictor of metastasis among men followed expectantly and those receiving postoperative ART and SRT. [15][16][17] CAPRA-S and Decipher have also been shown to potentially help in the selection of men for ART as opposed to SRT, but these studies have lacked an untreated postprostatectomy cohort and were subject to bias. Here, using a multi-institutional database, we evaluate the combination of clinico-pathological and genomic risk in the context of postoperative therapeutic choices including adjuvant and salvage therapy as well as expectant management of disease with adverse pathological features.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Postoperative Radiation in a Prostatectomy Cohort Adjusted for Clinical and Genomic Risk

Den

Yousefi

Trock

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n = 111), minimal residual disease (MRD) SRT (n = 70) and SRT (n = 83) were defined by PSA levels of o 0.2, 0.2-0.49 and ⩾ 0.5 ng ml − 1 , respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome. RESULTS: During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P o0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P = 0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. CONCLUSIONS: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials. Prostate Cancer and Prostatic Diseases INTRODUCTIONAggressive treatment approaches that have not yet been shown to improve overall survival are controversial within oncology, particularly in the management of men with prostate cancer (PCa). 1,2 Three randomized clinical trials in men with nonmetastatic PCa following surgical resection showed that treatment with adjuvant radiation therapy (ART) as compared with observation resulted in lower rates of biochemical recurrence, yet had conflicting impact on metastasis-free and overall survival. [3][4][5] Given the disparate findings, there has been an increase in utilization of salvage radiation therapy (SRT) 6 with concomitant decrease in ART, despite no randomized prospective trial evidence supporting this clinical decision. Although multiple randomized clinical trials are ongoing, 7,8 results are not expected for several years. Thus, patients and physicians are left with mu...

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Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men

Cited by 211 publications

References 39 publications

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO‐IMPACT study

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO‐IMPACT study

Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence

Efficacy of Postoperative Radiation in a Prostatectomy Cohort Adjusted for Clinical and Genomic Risk

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