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Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes
Abstract Background Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinic...
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Published in: | European urology 2011-12, Vol.60 (6), p.1133-1139 |
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description | Abstract Background Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participants This retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. Intervention Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. Measurements A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitations Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels |
doi_str_mv | 10.1016/j.eururo.2011.08.029 |
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Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participants This retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. Intervention Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. Measurements A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitations Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels <70.2 Gy and 70.2–79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse–free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Conclusions Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.</description><identifier>ISSN: 0302-2838</identifier><identifier>EISSN: 1873-7560</identifier><identifier>DOI: 10.1016/j.eururo.2011.08.029</identifier><identifier>PMID: 21889832</identifier><identifier>CODEN: EUURAV</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>Aged ; Androgen Antagonists - therapeutic use ; Androgen deprivation therapy ; Antineoplastic Agents, Hormonal - therapeutic use ; Biological and medical sciences ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Dose escalation ; External beam radiotherapy ; Gynecology. Andrology. Obstetrics ; Humans ; Kaplan-Meier Estimate ; Male ; Male genital diseases ; Medical sciences ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Nephrology. Urinary tract diseases ; New York City ; Nomograms ; Proportional Hazards Models ; Prostate cancer ; Prostate-Specific Antigen - blood ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - mortality ; Prostatic Neoplasms - radiotherapy ; Prostatic Neoplasms - secondary ; PSA relapse–free survival ; Radiotherapy Dosage ; Radiotherapy, Conformal - adverse effects ; Radiotherapy, Conformal - mortality ; Radiotherapy, Intensity-Modulated - adverse effects ; Radiotherapy, Intensity-Modulated - mortality ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland ; Urology</subject><ispartof>European urology, 2011-12, Vol.60 (6), p.1133-1139</ispartof><rights>European Association of Urology</rights><rights>2011 European Association of Urology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.</rights><rights>2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c613t-63985dbddccaeca85208cba0f92566c56db845fb4e5e7c13b0d66efc7ddcee0f3</citedby><cites>FETCH-LOGICAL-c613t-63985dbddccaeca85208cba0f92566c56db845fb4e5e7c13b0d66efc7ddcee0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24746635$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21889832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zelefsky, Michael J</creatorcontrib><creatorcontrib>Pei, Xin</creatorcontrib><creatorcontrib>Chou, Joanne F</creatorcontrib><creatorcontrib>Schechter, Michael</creatorcontrib><creatorcontrib>Kollmeier, Marisa</creatorcontrib><creatorcontrib>Cox, Brett</creatorcontrib><creatorcontrib>Yamada, Yoshiya</creatorcontrib><creatorcontrib>Fidaleo, Anthony</creatorcontrib><creatorcontrib>Sperling, Dahlia</creatorcontrib><creatorcontrib>Happersett, Laura</creatorcontrib><creatorcontrib>Zhang, Zhigang</creatorcontrib><title>Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes</title><title>European urology</title><addtitle>Eur Urol</addtitle><description>Abstract Background Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participants This retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. Intervention Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. Measurements A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitations Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels <70.2 Gy and 70.2–79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse–free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Conclusions Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.</description><subject>Aged</subject><subject>Androgen Antagonists - therapeutic use</subject><subject>Androgen deprivation therapy</subject><subject>Antineoplastic Agents, Hormonal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy, Adjuvant</subject><subject>Disease-Free Survival</subject><subject>Dose escalation</subject><subject>External beam radiotherapy</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy</subject><subject>Neoplasm Staging</subject><subject>Nephrology. Urinary tract diseases</subject><subject>New York City</subject><subject>Nomograms</subject><subject>Proportional Hazards Models</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - blood</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - mortality</subject><subject>Prostatic Neoplasms - radiotherapy</subject><subject>Prostatic Neoplasms - secondary</subject><subject>PSA relapse–free survival</subject><subject>Radiotherapy Dosage</subject><subject>Radiotherapy, Conformal - adverse effects</subject><subject>Radiotherapy, Conformal - mortality</subject><subject>Radiotherapy, Intensity-Modulated - adverse effects</subject><subject>Radiotherapy, Intensity-Modulated - mortality</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><subject>Urology</subject><issn>0302-2838</issn><issn>1873-7560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqFksFu1DAQhiMEokvhDRDyhWOWcRw7Dgckum0BaVERXc6W40y6XjbxynZW2hvv0DfkSXC0pQUunGx55v9nPN9k2UsKcwpUvNnMcfSjd_MCKJ2DnENRP8pmVFYsr7iAx9kMGBR5IZk8yZ6FsAEAxmv2NDspqJS1ZMUsuz13AclFMHqro3UD6ZwnX7wLUUckCz0Y9OSrbq2La_R6d3ibothaE50PxHVk6YabfIW-J2fWmTX2NlmR1dgnn4UbondbooeWnNtkOUTyGaNOt4Dh54_bS49Irke_t_skuhqjcT2G59mTTm8Dvrg7T7Nvlxerxcd8efXh0-L9MjeCspgLVkveNm1rjEajJS9AmkZDVxdcCMNF28iSd02JHCtDWQOtENiZKikQoWOn2buj725sekyPqVu9VTtve-0Pymmr_o4Mdq1u3F6VwCrKeTIojwYmDSx47O61FNQESW3UEZKaICmQKkFKsld_1r0X_aaSEl7fJegJTOcTBhse8sqqFILxhw9gmtLeolfBWEzIWuvRRNU6-79O_jUwWztMBL_jAcPGjX5IBBRVoVCgrqeFmvaJUgBZVzX7BXu4zh0</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Zelefsky, Michael J</creator><creator>Pei, Xin</creator><creator>Chou, Joanne F</creator><creator>Schechter, Michael</creator><creator>Kollmeier, Marisa</creator><creator>Cox, Brett</creator><creator>Yamada, Yoshiya</creator><creator>Fidaleo, Anthony</creator><creator>Sperling, Dahlia</creator><creator>Happersett, Laura</creator><creator>Zhang, Zhigang</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20111201</creationdate><title>Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes</title><author>Zelefsky, Michael J ; Pei, Xin ; Chou, Joanne F ; Schechter, Michael ; Kollmeier, Marisa ; Cox, Brett ; Yamada, Yoshiya ; Fidaleo, Anthony ; Sperling, Dahlia ; Happersett, Laura ; Zhang, Zhigang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c613t-63985dbddccaeca85208cba0f92566c56db845fb4e5e7c13b0d66efc7ddcee0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aged</topic><topic>Androgen Antagonists - therapeutic use</topic><topic>Androgen deprivation therapy</topic><topic>Antineoplastic Agents, Hormonal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy, Adjuvant</topic><topic>Disease-Free Survival</topic><topic>Dose escalation</topic><topic>External beam radiotherapy</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoadjuvant Therapy</topic><topic>Neoplasm Staging</topic><topic>Nephrology. Urinary tract diseases</topic><topic>New York City</topic><topic>Nomograms</topic><topic>Proportional Hazards Models</topic><topic>Prostate cancer</topic><topic>Prostate-Specific Antigen - blood</topic><topic>Prostatic Neoplasms - immunology</topic><topic>Prostatic Neoplasms - mortality</topic><topic>Prostatic Neoplasms - radiotherapy</topic><topic>Prostatic Neoplasms - secondary</topic><topic>PSA relapse–free survival</topic><topic>Radiotherapy Dosage</topic><topic>Radiotherapy, Conformal - adverse effects</topic><topic>Radiotherapy, Conformal - mortality</topic><topic>Radiotherapy, Intensity-Modulated - adverse effects</topic><topic>Radiotherapy, Intensity-Modulated - mortality</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zelefsky, Michael J</creatorcontrib><creatorcontrib>Pei, Xin</creatorcontrib><creatorcontrib>Chou, Joanne F</creatorcontrib><creatorcontrib>Schechter, Michael</creatorcontrib><creatorcontrib>Kollmeier, Marisa</creatorcontrib><creatorcontrib>Cox, Brett</creatorcontrib><creatorcontrib>Yamada, Yoshiya</creatorcontrib><creatorcontrib>Fidaleo, Anthony</creatorcontrib><creatorcontrib>Sperling, Dahlia</creatorcontrib><creatorcontrib>Happersett, Laura</creatorcontrib><creatorcontrib>Zhang, Zhigang</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European urology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zelefsky, Michael J</au><au>Pei, Xin</au><au>Chou, Joanne F</au><au>Schechter, Michael</au><au>Kollmeier, Marisa</au><au>Cox, Brett</au><au>Yamada, Yoshiya</au><au>Fidaleo, Anthony</au><au>Sperling, Dahlia</au><au>Happersett, Laura</au><au>Zhang, Zhigang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes</atitle><jtitle>European urology</jtitle><addtitle>Eur Urol</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>60</volume><issue>6</issue><spage>1133</spage><epage>1139</epage><pages>1133-1139</pages><issn>0302-2838</issn><eissn>1873-7560</eissn><coden>EUURAV</coden><abstract>Abstract Background Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participants This retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. Intervention Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. Measurements A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitations Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels <70.2 Gy and 70.2–79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse–free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Conclusions Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.</abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>21889832</pmid><doi>10.1016/j.eururo.2011.08.029</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Aged Androgen Antagonists - therapeutic use Androgen deprivation therapy Antineoplastic Agents, Hormonal - therapeutic use Biological and medical sciences Chemotherapy, Adjuvant Disease-Free Survival Dose escalation External beam radiotherapy Gynecology. Andrology. Obstetrics Humans Kaplan-Meier Estimate Male Male genital diseases Medical sciences Middle Aged Neoadjuvant Therapy Neoplasm Staging Nephrology. Urinary tract diseases New York City Nomograms Proportional Hazards Models Prostate cancer Prostate-Specific Antigen - blood Prostatic Neoplasms - immunology Prostatic Neoplasms - mortality Prostatic Neoplasms - radiotherapy Prostatic Neoplasms - secondary PSA relapse–free survival Radiotherapy Dosage Radiotherapy, Conformal - adverse effects Radiotherapy, Conformal - mortality Radiotherapy, Intensity-Modulated - adverse effects Radiotherapy, Intensity-Modulated - mortality Retrospective Studies Risk Assessment Risk Factors Time Factors Treatment Outcome Tumors Tumors of the urinary system Urinary tract. Prostate gland Urology |
title | Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases–Free Survival Outcomes |
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