Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer

Ross, Ashley E.; D’Amico, Anthony V.; Freedland, Stephen J.

doi:10.1038/pcan.2015.31

Cited by 80 publications

(54 citation statements)

References 54 publications

(69 reference statements)

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“…The 22‐gene Decipher predicts metastasis following RP (Erho et al ., 2013; Karnes et al ., 2013; Klein et al ., 2016). While these and other biomarkers assist decision making and thus improve patient management, their clinical application requires further validation (Lamy et al ., 2017; Martin, 2016; McGrath et al ., 2016; Patel and Gnanapragasam, 2016; Ross et al ., 2016; Zhuang and Johnson, 2016). There is a clear need to improve our ability to stratify PCs with high risk of recurrence following RP.…”

Section: Introductionmentioning

confidence: 99%

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence

Jiang

Mei

et al. 2018

Molecular Oncology

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We report here numerous novel genes and multiple new signatures which robustly predict prostate cancer (PC) recurrence. We extracted 696 differentially expressed genes relative to a reported PC signature from the TCGA dataset (n = 492) and built a 15‐gene signature (SigMuc1NW) using Elastic‐net with 10‐fold cross‐validation through analyzing their expressions at 1.5 standard deviation/SD below and 2 SD above a population mean. SigMuc1NW predicts biochemical recurrence (BCR) following surgery with 56.4% sensitivity, 72.6% specificity, and 63.24 median months disease free (MMDF) (P = 1.12e‐12). The prediction accuracy is improved with the use of SigMuc1NW's cutpoint (P = 3e‐15) and is further enhanced (sensitivity 67%, specificity 75.7%, MMDF 45.2, P = 0) when all 15 genes were analyzed through their cutpoints instead of their SDs. These genes individually associate with BCR using either SD or cutpoint as the cutoff points. Eight of 15 genes are individual risk factors after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. Eleven of 15 genes are novel to PC. SigMuc1NW discriminates BCR with time‐dependent AUC (tAUC) values of 76.6% at 11.5 months (76.6%–11.5 m), 73.8%‐22.3 m, 78.5%‐32.1 m, and 76.4%–48.4 m. SigMuc1NW is correlated with adverse features of PC, high Gleason scores (odds ratio/OR 1.48, P < 2e‐16), and advanced tumor stages (OR 1.33, P = 4.37e‐13). SigMuc1NW remains an independent risk factor of BCR (HR 2.44, 95% CI 1.53–3.87, P = 1.62e‐4) after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. In an independent PC (MSKCC) cohort (n = 140), these 15 genes were altered in PC vs normal tissue, metastatic PCs vs primary PCs, and recurrent PCs vs nonrecurrent PCs. Importantly, a 10‐gene subsignature SigMuc1NW1 predicts BCR in MSKCC (P = 3.11e‐15) and TCGA (P = 3.13e‐12); SigMuc1NW1 discriminates BCR at 18.4 m with tAUC as 82.5%. Collectively, our analyses support SigMuc1NW as a novel and robust signature in predicting BCR of PC.

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Section: Introductionmentioning

confidence: 99%

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence

Jiang

Mei

et al. 2018

Molecular Oncology

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“…Based on existing data, however, some of which is derived from conservatively managed cohorts, it is both reasonable and biologically plausible to consider some molecular tests in the AS setting. 18 Here we briefly review the molecular tests proposed for use in decisions about AS (Table 3). …”

Section: Molecular Testing In Active Surveillancementioning

confidence: 99%

“…17 Furthermore, clinically validated molecular tests have established a prognostic role in some clinical contexts. 18 These platforms, along with a recently updated system of pathologic grading, present a unique opportunity to improve the practice of AS. 19,20 This article aims to review the contemporary practice of AS, including trends in use, outcomes, pathologic grading, MRI, and tissue-based molecular testing.…”

mentioning

confidence: 99%

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools

Tosoian¹,

Loeb²,

Epstein³

et al. 2016

American Society of Clinical Oncology Educational Book

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Active surveillance (AS) has emerged as a standard management option for men with very low-risk and low-risk prostate cancer, and contemporary data indicate that use of AS is increasing in the United States and abroad. In the favorable-risk population, reports from multiple prospective cohorts indicate a less than 1% likelihood of metastatic disease and prostate cancer-specific mortality over intermediate-term follow-up (median 5 to 6 years). Higher-risk men participating in AS appear to be at increased risk of adverse outcomes, but these populations have not been adequately studied to this point. Although monitoring on AS largely relies on serial prostate biopsy, a procedure associated with significant morbidity, there is a need for improved diagnostic tools for patient selection and monitoring. Revisions from the 2014 International Society of Urologic Pathology consensus conference have yielded a more intuitive reporting system and detailed reporting of low-intermediate grade tumors, which should facilitate the practice of AS. Meanwhile, emerging modalities such as multiparametric magnetic resonance imaging and tissue-based molecular testing have shown prognostic value in some populations. At this time, however, these instruments have not been sufficiently studied to consider their routine, standardized use in the AS setting. Future studies should seek to identify those platforms most informative in the AS population and propose a strategy by which promising diagnostic tools can be safely and efficiently incorporated into clinical practice.

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“…11,12 More recently, tissue-based genomic testing in the form of Decipher has been developed and validated to predict metastasis-free survival. 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.…”

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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Which, when and why? Rational use of tissue-based molecular testing in localized prostate cancer

Cited by 80 publications

References 54 publications

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools

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

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