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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
Main Authors: Zelefsky, Michael J, Pei, Xin, Chou, Joanne F, Schechter, Michael, Kollmeier, Marisa, Cox, Brett, Yamada, Yoshiya, Fidaleo, Anthony, Sperling, Dahlia, Happersett, Laura, Zhang, Zhigang
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creator Zelefsky, Michael J
Pei, Xin
Chou, Joanne F
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Sperling, Dahlia
Happersett, Laura
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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 &gt;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 &lt;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&amp;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 &gt;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 &lt;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. 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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 &gt;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 &lt;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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