Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy

Berlin, Alejandro; Murgić, Jure; Hosni, Ali; Pintilie, Melania; Salcedo, Adriana; Fraser, Michael; Kamel‐Reid, Suzanne; Zhang, Jingbin; Wang, Qiqi; Ch’ng, Carolyn; Deheshi, Samineh; Davicioni, Elai; Kwast, Theodorus van der; Boutros, Paul C.; Bristow, Robert G.; Chua, Melvin L.K.

doi:10.1016/j.ijrobp.2018.08.030

Cited by 39 publications

(18 citation statements)

References 26 publications

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“…As the concept of personalized therapy becomes increasingly popular, paNents' geneNc variaNons and transcriptomic and proteomic tumour data are becoming more readily available, providing increased opportuniNes for novel target discovery (279) and the use of genomic techniques to guide radiaNon decisions (240). Several radiotherapy sensiNvity-associated gene signatures have been reported for prostate cancer (241,242), although further clinical validaNon, along with benefit from clinical uNlity, is awaited. Nevertheless, it is an exciNng possibility that pre-treatment analysis of paNent samples might enable accurate predicNon of radiotherapy response, thereby contribuNng to decision-making regarding selecNon of radiotherapy versus alternaNve treatments such as surgery.…”

Section: [H2}radiotherapy Sensinvity Gene Signaturesmentioning

confidence: 99%

Harnessing the potential of multimodal radiotherapy in prostate cancer

et al. 2020

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in combinaNon with androgen deprivaNon therapy (ADT) is a standard treatment opNon for men with localized and locally advanced prostate cancer. However, emerging clinical evidence suggests that radiotherapy could be incorporated into mulNmodality therapy regimens beyond ADT, in combinaNons that include chemotherapy, radiosensiNzing agents, immunotherapy, and surgery for localized and locally advanced prostate cancer, as well as in paNents with oligometastaNc disease where the low metastaNc burden in parNcular may be treatable with these combinaNons. This mulNmodal approach is increasingly recognized to offer considerable clinical benefit, such as increased anN-tumour effects and survival benefits. Thus, radiotherapy is becoming a key component of mulNmodal therapy for many stages of prostate cancer, parNcularly for paNents with oligometastaNc disease. Key points-Radiotherapy combined with androgen deprivaNon therapy (ADT) is a common treatment opNon for men with prostate cancer.

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Section: [H2}radiotherapy Sensinvity Gene Signaturesmentioning

confidence: 99%

Harnessing the potential of multimodal radiotherapy in prostate cancer

et al. 2020

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“…Moreover, Cindices were improved as compared to the NCCN and CAPRA-risk classification systems. In 2019, Berlin et al demonstrated that among men with favorable-IR and unfavorable-IR prostate cancer treated with EBRT alone, the clinical-genomic risk classification better predicted distant metastasis than NCCN risk groups alone, suggesting this approach may better identify IR patients who would benefit from the addition of ADT to EBRT (13). Ultimately, further investigations will be useful to evaluate the incorporation of genomic classifiers into management decisions.…”

Section: Discussionmentioning

confidence: 99%

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy

et al. 2020

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PURPOSE: To validate the 2019 NCCN subgroups of favorable-and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification. METHODS: We included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis. RESULTS: Of 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3e214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00e4.10; p ! 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78e5.50, p ! 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6e6.1%) vs. 17.0% (95% CI, 13.6e20.5%; p ! 0.001), and for distant metastasis were 1.6% (95% CI, 0.5e2.6%) vs. 5.4% (95% CI, 3.3e7.4%; p ! 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54e3.36; p ! 0.001) and 2e3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89e6.76; p ! 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34e4.53, p 5 0.004; 2e3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49e9.10, p ! 0.001). CONCLUSIONS: These findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted.

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“…Due to low event rates and the lack of follow-up data in GRID, oncologic endpoints such as biochemical recurrence, metastasis, and mortality were not evaluated, but these endpoints must be the focus of future studies in the F-IR group. It should be noted that Decipher has already been extensively validated to predict these distal endpoints in higher risk cohorts [31,32]. In the meantime, AP does continue to drive clinical decision-making, particularly for men with lower clinical risk at diagnosis, and is still the focus of ongoing biomarker studies.…”

Section: Discussionmentioning

confidence: 99%

Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance

Herlemann

Huang

Alam

et al. 2019

Prostate Cancer Prostatic Dis

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Background We aimed to validate Decipher to predict adverse pathology (AP) at radical prostatectomy (RP) in men with National Comprehensive Cancer Network (NCCN) favorable-intermediate risk (F-IR) prostate cancer (PCa), and to better select FIR candidates for active surveillance (AS). Methods In all, 647 patients diagnosed with NCCN very low/low risk (VL/LR) or FIR prostate cancer were identified from a multi-institutional PCa biopsy database; all underwent RP with complete postoperative clinicopathological information and Decipher genomic risk scores. The performance of all risk assessment tools was evaluated using logistic regression model for the endpoint of AP, defined as grade group 3−5, pT3b or higher, or lymph node invasion. Results The median age was 61 years (interquartile range 56-66) for 220 patients with NCCN FIR disease, 53% classified as low-risk by Cancer of the Prostate Risk Assessment (CAPRA 0−2) and 47% as intermediate-risk (CAPRA 3−5). Decipher classified 79%, 13% and 8% of men as low-, intermediate-and high-risk with 13%, 10%, and 41% rate of AP, respectively. Decipher was an independent predictor of AP with an odds ratio of 1.34 per 0.1 unit increased (p value = 0.002) and remained significant when adjusting by CAPRA. Notably, FIR with Decipher low or intermediate score did not associate with significantly higher odds of AP compared to VL/LR. Conclusions NCCN risk groups, including FIR , are highly heterogeneous and should be replaced with multivariable riskstratification. In particular, incorporating Decipher may be useful for safely expanding the use of AS in this patient population.

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Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy

Abstract: We demonstrated the accuracy of the GC for predicting disease recurrence in IR-PCa treated with DE-IGRT alone. Our findings highlight the need to evaluate this GC in a prospective clinical trial investigating the role of ADT-RT in clinicogenomic-defined IR-PCa subgroups.

Cited by 39 publications

References 26 publications

Harnessing the potential of multimodal radiotherapy in prostate cancer

Harnessing the potential of multimodal radiotherapy in prostate cancer

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy

Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance

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