Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials
The Prostate Subtyping Classifier is both a prognostic and a predictive biomarker in patients with high-risk localized prostate cancer undergoing radiotherapy. In addition to improving risk prediction, this classifier also allows physicians to select which patients will benefit from prolonged androg...
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| creator | Patel, Krishnan R. Nguyen, Paul L. Proudfoot, James A. Liu, Yang Pra, Alan Dal Spratt, Daniel E. Pollack, Alan Sandler, Howard M. Efstathiou, Jason A. Lawton, Colleen Simko, Jeffry P. Rosenthal, Seth A. Zeitzer, Kenneth L. Mendez, Lucas C. Hartford, Alan C. Hall, William A. Desai, Anand B. Pugh, Stephanie L. Davicioni, Elai Tran, Phuoc T. Feng, Felix Y. |
| description | The Prostate Subtyping Classifier is both a prognostic and a predictive biomarker in patients with high-risk localized prostate cancer undergoing radiotherapy. In addition to improving risk prediction, this classifier also allows physicians to select which patients will benefit from prolonged androgen deprivation therapy.
Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24–28 mo) versus short-term (ST; 4 mo) ADT.
Biopsy samples from three randomized, phase 3 trials–NRG/RTOG 9202, 9413, and 9902–were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models.
On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3–2.5], p |
| doi_str_mv | 10.1016/j.euo.2024.10.017 |
| format | Article |
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Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24–28 mo) versus short-term (ST; 4 mo) ADT.
Biopsy samples from three randomized, phase 3 trials–NRG/RTOG 9202, 9413, and 9902–were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models.
On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3–2.5], p < 0.001), PCSM (subdistribution HR 2.4 [95% confidence interval {CI} 1.4–4.1], p = 0.001), and OS (HR 1.8 [1.3–2.6], p < 0.001). Ten-year PCSM was 15% better for the luminal subtype than for the basal subtype (11% [95% CI 6–15%] vs 26% [95% CI 17–35%]). A significant interaction between ADT duration (LT vs ST) and PSC subtype (basal vs luminal) was observed for PCSM (pinteraction = 0.008), leading to the observation that 10-yr PCSM was improved with LT-ADT only in patients with basal-type tumors (5% [95% CI 0–11%] vs 42% [29–56%], p < 0.001). Improvements in 10-yr RMST with LT-ADT were greater for basal tumors for oncologic endpoints with the exception of OCM.
PSC is both a prognostic and a predictive biomarker for patients who benefit from LT-ADT. PSC subtypes may be used to personalize ADT recommendations for patients with high-risk PCa, pending further validation in a prospective study.
In this study, we tried to understand the usefulness of a new genomic test in patients with high-risk, nonmetastatic prostate cancer who underwent radiation therapy and hormonal therapy (HT). We found that this test can help determine a patient’s prognosis (eg, a patient’s chance of having the cancer return) and, more importantly, personalize treatment decisions by understanding which patients may benefit from long-term HT. This has the potential to save many patients who may not benefit from prolonged HT from “overtreatment” or the unnecessary side effects of such treatment.</description><identifier>ISSN: 2588-9311</identifier><identifier>EISSN: 2588-9311</identifier><identifier>DOI: 10.1016/j.euo.2024.10.017</identifier><identifier>PMID: 39542826</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Androgen deprivation therapy ; Biomarker ; Decipher ; Genomic classifier ; High risk ; Predictive biomarker ; Prognosis ; Prostate cancer ; Prostate subtyping classifier</subject><ispartof>European urology oncology, 2024-11</ispartof><rights>2024 European Association of Urology</rights><rights>Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1506-94299731edbec36a78181ce185b8f807caab94539f37041af8f68f9b5d2721003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39542826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Patel, Krishnan R.</creatorcontrib><creatorcontrib>Nguyen, Paul L.</creatorcontrib><creatorcontrib>Proudfoot, James A.</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Pra, Alan Dal</creatorcontrib><creatorcontrib>Spratt, Daniel E.</creatorcontrib><creatorcontrib>Pollack, Alan</creatorcontrib><creatorcontrib>Sandler, Howard M.</creatorcontrib><creatorcontrib>Efstathiou, Jason A.</creatorcontrib><creatorcontrib>Lawton, Colleen</creatorcontrib><creatorcontrib>Simko, Jeffry P.</creatorcontrib><creatorcontrib>Rosenthal, Seth A.</creatorcontrib><creatorcontrib>Zeitzer, Kenneth L.</creatorcontrib><creatorcontrib>Mendez, Lucas C.</creatorcontrib><creatorcontrib>Hartford, Alan C.</creatorcontrib><creatorcontrib>Hall, William A.</creatorcontrib><creatorcontrib>Desai, Anand B.</creatorcontrib><creatorcontrib>Pugh, Stephanie L.</creatorcontrib><creatorcontrib>Davicioni, Elai</creatorcontrib><creatorcontrib>Tran, Phuoc T.</creatorcontrib><creatorcontrib>Feng, Felix Y.</creatorcontrib><title>Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials</title><title>European urology oncology</title><addtitle>Eur Urol Oncol</addtitle><description>The Prostate Subtyping Classifier is both a prognostic and a predictive biomarker in patients with high-risk localized prostate cancer undergoing radiotherapy. In addition to improving risk prediction, this classifier also allows physicians to select which patients will benefit from prolonged androgen deprivation therapy.
Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24–28 mo) versus short-term (ST; 4 mo) ADT.
Biopsy samples from three randomized, phase 3 trials–NRG/RTOG 9202, 9413, and 9902–were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models.
On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3–2.5], p < 0.001), PCSM (subdistribution HR 2.4 [95% confidence interval {CI} 1.4–4.1], p = 0.001), and OS (HR 1.8 [1.3–2.6], p < 0.001). Ten-year PCSM was 15% better for the luminal subtype than for the basal subtype (11% [95% CI 6–15%] vs 26% [95% CI 17–35%]). A significant interaction between ADT duration (LT vs ST) and PSC subtype (basal vs luminal) was observed for PCSM (pinteraction = 0.008), leading to the observation that 10-yr PCSM was improved with LT-ADT only in patients with basal-type tumors (5% [95% CI 0–11%] vs 42% [29–56%], p < 0.001). Improvements in 10-yr RMST with LT-ADT were greater for basal tumors for oncologic endpoints with the exception of OCM.
PSC is both a prognostic and a predictive biomarker for patients who benefit from LT-ADT. PSC subtypes may be used to personalize ADT recommendations for patients with high-risk PCa, pending further validation in a prospective study.
In this study, we tried to understand the usefulness of a new genomic test in patients with high-risk, nonmetastatic prostate cancer who underwent radiation therapy and hormonal therapy (HT). We found that this test can help determine a patient’s prognosis (eg, a patient’s chance of having the cancer return) and, more importantly, personalize treatment decisions by understanding which patients may benefit from long-term HT. This has the potential to save many patients who may not benefit from prolonged HT from “overtreatment” or the unnecessary side effects of such treatment.</description><subject>Androgen deprivation therapy</subject><subject>Biomarker</subject><subject>Decipher</subject><subject>Genomic classifier</subject><subject>High risk</subject><subject>Predictive biomarker</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Prostate subtyping classifier</subject><issn>2588-9311</issn><issn>2588-9311</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1DAUhS0EolXpA7BBd8mimfonPzasphFMkSqmKsPachx7xkMST-0EKS_Ds-LRlKorVte--u7Rvecg9J7gBcGkvN4vzOQXFNM8_ReYVK_QOS04zwQj5PWL9xm6jHGPMU4sJpi-RWdMFDnltDxHf26cP8Q5a1Q0LdyoqLqsm3o3qA5-TM04H9ywhbpTMTrrTAA3wK3b7rLg4i-4Dz6OajRQq0Gb8AmWUPu-cUPSWiaJOboI3sK4M_D9YQXrQfvOb-frh816BSItdAUiJ-wK1NCCEJjC_S5tAgw2wakuvkNvbCrm8qleoJ9fv2zq2-xuvfpWL-8yTQpcZiKnQlSMmLYxmpWq4oQTbQgvGm45rrRSjcgLJiyrcE6U5bbkVjRFSytKMGYX6ONJ9xD842TiKHsXtek6NRg_RckI5ZzmybWEkhOq0_ExGCsPwfUqzJJgeUxG7mVKRh6TObZSMmnmw5P81PSmfZ74l0MCPp8Ak478nXyWUTuTPG1dMHqUrXf_kf8LY6mauQ</recordid><startdate>20241113</startdate><enddate>20241113</enddate><creator>Patel, Krishnan R.</creator><creator>Nguyen, Paul L.</creator><creator>Proudfoot, James A.</creator><creator>Liu, Yang</creator><creator>Pra, Alan Dal</creator><creator>Spratt, Daniel E.</creator><creator>Pollack, Alan</creator><creator>Sandler, Howard M.</creator><creator>Efstathiou, Jason A.</creator><creator>Lawton, Colleen</creator><creator>Simko, Jeffry P.</creator><creator>Rosenthal, Seth A.</creator><creator>Zeitzer, Kenneth L.</creator><creator>Mendez, Lucas C.</creator><creator>Hartford, Alan C.</creator><creator>Hall, William A.</creator><creator>Desai, Anand B.</creator><creator>Pugh, Stephanie L.</creator><creator>Davicioni, Elai</creator><creator>Tran, Phuoc T.</creator><creator>Feng, Felix Y.</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20241113</creationdate><title>Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials</title><author>Patel, Krishnan R. ; Nguyen, Paul L. ; Proudfoot, James A. ; Liu, Yang ; Pra, Alan Dal ; Spratt, Daniel E. ; Pollack, Alan ; Sandler, Howard M. ; Efstathiou, Jason A. ; Lawton, Colleen ; Simko, Jeffry P. ; Rosenthal, Seth A. ; Zeitzer, Kenneth L. ; Mendez, Lucas C. ; Hartford, Alan C. ; Hall, William A. ; Desai, Anand B. ; Pugh, Stephanie L. ; Davicioni, Elai ; Tran, Phuoc T. ; Feng, Felix Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1506-94299731edbec36a78181ce185b8f807caab94539f37041af8f68f9b5d2721003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Androgen deprivation therapy</topic><topic>Biomarker</topic><topic>Decipher</topic><topic>Genomic classifier</topic><topic>High risk</topic><topic>Predictive biomarker</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Prostate subtyping classifier</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Patel, Krishnan R.</creatorcontrib><creatorcontrib>Nguyen, Paul L.</creatorcontrib><creatorcontrib>Proudfoot, James A.</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Pra, Alan Dal</creatorcontrib><creatorcontrib>Spratt, Daniel E.</creatorcontrib><creatorcontrib>Pollack, Alan</creatorcontrib><creatorcontrib>Sandler, Howard M.</creatorcontrib><creatorcontrib>Efstathiou, Jason A.</creatorcontrib><creatorcontrib>Lawton, Colleen</creatorcontrib><creatorcontrib>Simko, Jeffry P.</creatorcontrib><creatorcontrib>Rosenthal, Seth A.</creatorcontrib><creatorcontrib>Zeitzer, Kenneth L.</creatorcontrib><creatorcontrib>Mendez, Lucas C.</creatorcontrib><creatorcontrib>Hartford, Alan C.</creatorcontrib><creatorcontrib>Hall, William A.</creatorcontrib><creatorcontrib>Desai, Anand B.</creatorcontrib><creatorcontrib>Pugh, Stephanie L.</creatorcontrib><creatorcontrib>Davicioni, Elai</creatorcontrib><creatorcontrib>Tran, Phuoc T.</creatorcontrib><creatorcontrib>Feng, Felix Y.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European urology oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Patel, Krishnan R.</au><au>Nguyen, Paul L.</au><au>Proudfoot, James A.</au><au>Liu, Yang</au><au>Pra, Alan Dal</au><au>Spratt, Daniel E.</au><au>Pollack, Alan</au><au>Sandler, Howard M.</au><au>Efstathiou, Jason A.</au><au>Lawton, Colleen</au><au>Simko, Jeffry P.</au><au>Rosenthal, Seth A.</au><au>Zeitzer, Kenneth L.</au><au>Mendez, Lucas C.</au><au>Hartford, Alan C.</au><au>Hall, William A.</au><au>Desai, Anand B.</au><au>Pugh, Stephanie L.</au><au>Davicioni, Elai</au><au>Tran, Phuoc T.</au><au>Feng, Felix Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials</atitle><jtitle>European urology oncology</jtitle><addtitle>Eur Urol Oncol</addtitle><date>2024-11-13</date><risdate>2024</risdate><issn>2588-9311</issn><eissn>2588-9311</eissn><abstract>The Prostate Subtyping Classifier is both a prognostic and a predictive biomarker in patients with high-risk localized prostate cancer undergoing radiotherapy. In addition to improving risk prediction, this classifier also allows physicians to select which patients will benefit from prolonged androgen deprivation therapy.
Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24–28 mo) versus short-term (ST; 4 mo) ADT.
Biopsy samples from three randomized, phase 3 trials–NRG/RTOG 9202, 9413, and 9902–were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models.
On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3–2.5], p < 0.001), PCSM (subdistribution HR 2.4 [95% confidence interval {CI} 1.4–4.1], p = 0.001), and OS (HR 1.8 [1.3–2.6], p < 0.001). Ten-year PCSM was 15% better for the luminal subtype than for the basal subtype (11% [95% CI 6–15%] vs 26% [95% CI 17–35%]). A significant interaction between ADT duration (LT vs ST) and PSC subtype (basal vs luminal) was observed for PCSM (pinteraction = 0.008), leading to the observation that 10-yr PCSM was improved with LT-ADT only in patients with basal-type tumors (5% [95% CI 0–11%] vs 42% [29–56%], p < 0.001). Improvements in 10-yr RMST with LT-ADT were greater for basal tumors for oncologic endpoints with the exception of OCM.
PSC is both a prognostic and a predictive biomarker for patients who benefit from LT-ADT. PSC subtypes may be used to personalize ADT recommendations for patients with high-risk PCa, pending further validation in a prospective study.
In this study, we tried to understand the usefulness of a new genomic test in patients with high-risk, nonmetastatic prostate cancer who underwent radiation therapy and hormonal therapy (HT). We found that this test can help determine a patient’s prognosis (eg, a patient’s chance of having the cancer return) and, more importantly, personalize treatment decisions by understanding which patients may benefit from long-term HT. This has the potential to save many patients who may not benefit from prolonged HT from “overtreatment” or the unnecessary side effects of such treatment.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>39542826</pmid><doi>10.1016/j.euo.2024.10.017</doi></addata></record> |
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| subjects | Androgen deprivation therapy Biomarker Decipher Genomic classifier High risk Predictive biomarker Prognosis Prostate cancer Prostate subtyping classifier |
| title | Biopsy-based Basal-luminal Subtyping Classifier in High-risk Prostate Cancer: A Combined Analysis of the NRG Oncology/RTOG 9202, 9413, and 9902 Phase 3 Trials |
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