Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma
Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment. Data from 51 patients with CSI NS who experienc...
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Veröffentlicht in: | Journal of clinical oncology 2020-04, Vol.38 (12), p.1322-1331 |
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creator | Fischer, Stefanie Tandstad, Torgrim Cohn-Cedermark, Gabriella Thibault, Constance Vincenzi, Bruno Klingbiel, Dirk Albany, Costantine Necchi, Andrea Terbuch, Angelika Lorch, Anja Aparicio, Jorge Heidenreich, Axel Hentrich, Marcus Wheater, Matthew Langberg, Carl W Ståhl, Olof Fankhauser, Christian Daniel Hamid, Anis A Koutsoukos, Konstantinos Shamash, Jonathan White, Jeff Bokemeyer, Carsten Beyer, Jörg Gillessen, Silke |
description | Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.
Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.
Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year;
= .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.
Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years). |
doi_str_mv | 10.1200/JCO.19.01876 |
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Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.
Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year;
= .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.
Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).</description><identifier>ISSN: 0732-183X</identifier><identifier>EISSN: 1527-7755</identifier><identifier>DOI: 10.1200/JCO.19.01876</identifier><identifier>PMID: 31877087</identifier><language>eng</language><publisher>United States: American Society of Clinical Oncology</publisher><subject>Adult ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bleomycin - administration & dosage ; Chemotherapy, Adjuvant ; Cisplatin - administration & dosage ; Etoposide - administration & dosage ; Humans ; Male ; Neoplasm Staging ; Neoplasms, Germ Cell and Embryonal - drug therapy ; Neoplasms, Germ Cell and Embryonal - surgery ; Orchiectomy ; ORIGINAL REPORTS ; Progression-Free Survival ; Retrospective Studies ; Survival Rate ; Testicular Neoplasms - drug therapy ; Testicular Neoplasms - pathology ; Testicular Neoplasms - surgery ; Treatment Outcome</subject><ispartof>Journal of clinical oncology, 2020-04, Vol.38 (12), p.1322-1331</ispartof><rights>2019 by American Society of Clinical Oncology 2019 American Society of Clinical Oncology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-47243a414d71a38e50b69e882abda301b1b470858955d50b52c1a6a5cada9e693</citedby><cites>FETCH-LOGICAL-c422t-47243a414d71a38e50b69e882abda301b1b470858955d50b52c1a6a5cada9e693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,3716,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31877087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:143495723$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Fischer, Stefanie</creatorcontrib><creatorcontrib>Tandstad, Torgrim</creatorcontrib><creatorcontrib>Cohn-Cedermark, Gabriella</creatorcontrib><creatorcontrib>Thibault, Constance</creatorcontrib><creatorcontrib>Vincenzi, Bruno</creatorcontrib><creatorcontrib>Klingbiel, Dirk</creatorcontrib><creatorcontrib>Albany, Costantine</creatorcontrib><creatorcontrib>Necchi, Andrea</creatorcontrib><creatorcontrib>Terbuch, Angelika</creatorcontrib><creatorcontrib>Lorch, Anja</creatorcontrib><creatorcontrib>Aparicio, Jorge</creatorcontrib><creatorcontrib>Heidenreich, Axel</creatorcontrib><creatorcontrib>Hentrich, Marcus</creatorcontrib><creatorcontrib>Wheater, Matthew</creatorcontrib><creatorcontrib>Langberg, Carl W</creatorcontrib><creatorcontrib>Ståhl, Olof</creatorcontrib><creatorcontrib>Fankhauser, Christian Daniel</creatorcontrib><creatorcontrib>Hamid, Anis A</creatorcontrib><creatorcontrib>Koutsoukos, Konstantinos</creatorcontrib><creatorcontrib>Shamash, Jonathan</creatorcontrib><creatorcontrib>White, Jeff</creatorcontrib><creatorcontrib>Bokemeyer, Carsten</creatorcontrib><creatorcontrib>Beyer, Jörg</creatorcontrib><creatorcontrib>Gillessen, Silke</creatorcontrib><creatorcontrib>Global Germ-Cell Cancer Group</creatorcontrib><creatorcontrib>on behalf of the Global Germ-Cell Cancer Group</creatorcontrib><title>Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma</title><title>Journal of clinical oncology</title><addtitle>J Clin Oncol</addtitle><description>Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.
Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.
Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year;
= .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.
Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).</description><subject>Adult</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Bleomycin - administration & dosage</subject><subject>Chemotherapy, Adjuvant</subject><subject>Cisplatin - administration & dosage</subject><subject>Etoposide - administration & dosage</subject><subject>Humans</subject><subject>Male</subject><subject>Neoplasm Staging</subject><subject>Neoplasms, Germ Cell and Embryonal - drug therapy</subject><subject>Neoplasms, Germ Cell and Embryonal - surgery</subject><subject>Orchiectomy</subject><subject>ORIGINAL REPORTS</subject><subject>Progression-Free Survival</subject><subject>Retrospective Studies</subject><subject>Survival Rate</subject><subject>Testicular Neoplasms - drug therapy</subject><subject>Testicular Neoplasms - pathology</subject><subject>Testicular Neoplasms - surgery</subject><subject>Treatment Outcome</subject><issn>0732-183X</issn><issn>1527-7755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNpVkU9v1DAQxS0Eokvhxhn5A2y2dmzHzgVpiVooKqzEH8HNmiST1iWxo9hb1G-Py5aKnmY07zdvNHqEvOZsw0vGTj42uw2vN4wbXT0hK65KXWit1FOyYlqUBTfi5xF5EeM1Y1waoZ6TI5FhzYxekXm3T12YkIaBfkJPf7h0Rb_gCHPESLdDwoVu--v9DfhE340YptvO-TU9TWEO0fW4puB72rg4j5Ccp0NYaDM67zoY6dcEl0jP6efgI07OhwlekmcDjBFf3ddj8v3s9FvzobjYvT9vthdFJ8syFVKXUoDkstcchEHF2qpGY0poexCMt7yV-QNlaqX6LKqy41CB6qCHGqtaHJPi4Bt_47xv7by4CZZbG8DZ-9Gv3KGVWlZKZP7tgc_KhH2HPi0wPlp7rHh3ZS_DjdW8ktKYbLA-GHRLiHHB4WGXM3uXlM1JWV7bv0ll_M3_9x7gf9GIP31okIM</recordid><startdate>20200420</startdate><enddate>20200420</enddate><creator>Fischer, Stefanie</creator><creator>Tandstad, Torgrim</creator><creator>Cohn-Cedermark, Gabriella</creator><creator>Thibault, Constance</creator><creator>Vincenzi, Bruno</creator><creator>Klingbiel, Dirk</creator><creator>Albany, Costantine</creator><creator>Necchi, Andrea</creator><creator>Terbuch, Angelika</creator><creator>Lorch, Anja</creator><creator>Aparicio, Jorge</creator><creator>Heidenreich, Axel</creator><creator>Hentrich, Marcus</creator><creator>Wheater, Matthew</creator><creator>Langberg, Carl W</creator><creator>Ståhl, Olof</creator><creator>Fankhauser, Christian Daniel</creator><creator>Hamid, Anis A</creator><creator>Koutsoukos, Konstantinos</creator><creator>Shamash, Jonathan</creator><creator>White, Jeff</creator><creator>Bokemeyer, Carsten</creator><creator>Beyer, Jörg</creator><creator>Gillessen, Silke</creator><general>American Society of Clinical Oncology</general><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><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20200420</creationdate><title>Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma</title><author>Fischer, Stefanie ; Tandstad, Torgrim ; Cohn-Cedermark, Gabriella ; Thibault, Constance ; Vincenzi, Bruno ; Klingbiel, Dirk ; Albany, Costantine ; Necchi, Andrea ; Terbuch, Angelika ; Lorch, Anja ; Aparicio, Jorge ; Heidenreich, Axel ; Hentrich, Marcus ; Wheater, Matthew ; Langberg, Carl W ; Ståhl, Olof ; Fankhauser, Christian Daniel ; Hamid, Anis A ; Koutsoukos, Konstantinos ; Shamash, Jonathan ; White, Jeff ; Bokemeyer, Carsten ; Beyer, Jörg ; Gillessen, Silke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-47243a414d71a38e50b69e882abda301b1b470858955d50b52c1a6a5cada9e693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Bleomycin - administration & dosage</topic><topic>Chemotherapy, Adjuvant</topic><topic>Cisplatin - administration & dosage</topic><topic>Etoposide - administration & dosage</topic><topic>Humans</topic><topic>Male</topic><topic>Neoplasm Staging</topic><topic>Neoplasms, Germ Cell and Embryonal - drug therapy</topic><topic>Neoplasms, Germ Cell and Embryonal - surgery</topic><topic>Orchiectomy</topic><topic>ORIGINAL REPORTS</topic><topic>Progression-Free Survival</topic><topic>Retrospective Studies</topic><topic>Survival Rate</topic><topic>Testicular Neoplasms - drug therapy</topic><topic>Testicular Neoplasms - pathology</topic><topic>Testicular Neoplasms - surgery</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fischer, Stefanie</creatorcontrib><creatorcontrib>Tandstad, Torgrim</creatorcontrib><creatorcontrib>Cohn-Cedermark, Gabriella</creatorcontrib><creatorcontrib>Thibault, Constance</creatorcontrib><creatorcontrib>Vincenzi, Bruno</creatorcontrib><creatorcontrib>Klingbiel, Dirk</creatorcontrib><creatorcontrib>Albany, Costantine</creatorcontrib><creatorcontrib>Necchi, Andrea</creatorcontrib><creatorcontrib>Terbuch, Angelika</creatorcontrib><creatorcontrib>Lorch, Anja</creatorcontrib><creatorcontrib>Aparicio, Jorge</creatorcontrib><creatorcontrib>Heidenreich, Axel</creatorcontrib><creatorcontrib>Hentrich, Marcus</creatorcontrib><creatorcontrib>Wheater, Matthew</creatorcontrib><creatorcontrib>Langberg, Carl W</creatorcontrib><creatorcontrib>Ståhl, Olof</creatorcontrib><creatorcontrib>Fankhauser, Christian Daniel</creatorcontrib><creatorcontrib>Hamid, Anis A</creatorcontrib><creatorcontrib>Koutsoukos, Konstantinos</creatorcontrib><creatorcontrib>Shamash, Jonathan</creatorcontrib><creatorcontrib>White, Jeff</creatorcontrib><creatorcontrib>Bokemeyer, Carsten</creatorcontrib><creatorcontrib>Beyer, Jörg</creatorcontrib><creatorcontrib>Gillessen, Silke</creatorcontrib><creatorcontrib>Global Germ-Cell Cancer Group</creatorcontrib><creatorcontrib>on behalf of the Global Germ-Cell Cancer Group</creatorcontrib><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><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fischer, Stefanie</au><au>Tandstad, Torgrim</au><au>Cohn-Cedermark, Gabriella</au><au>Thibault, Constance</au><au>Vincenzi, Bruno</au><au>Klingbiel, Dirk</au><au>Albany, Costantine</au><au>Necchi, Andrea</au><au>Terbuch, Angelika</au><au>Lorch, Anja</au><au>Aparicio, Jorge</au><au>Heidenreich, Axel</au><au>Hentrich, Marcus</au><au>Wheater, Matthew</au><au>Langberg, Carl W</au><au>Ståhl, Olof</au><au>Fankhauser, Christian Daniel</au><au>Hamid, Anis A</au><au>Koutsoukos, Konstantinos</au><au>Shamash, Jonathan</au><au>White, Jeff</au><au>Bokemeyer, Carsten</au><au>Beyer, Jörg</au><au>Gillessen, Silke</au><aucorp>Global Germ-Cell Cancer Group</aucorp><aucorp>on behalf of the Global Germ-Cell Cancer Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma</atitle><jtitle>Journal of clinical oncology</jtitle><addtitle>J Clin Oncol</addtitle><date>2020-04-20</date><risdate>2020</risdate><volume>38</volume><issue>12</issue><spage>1322</spage><epage>1331</epage><pages>1322-1331</pages><issn>0732-183X</issn><eissn>1527-7755</eissn><abstract>Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.
Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.
Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year;
= .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.
Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).</abstract><cop>United States</cop><pub>American Society of Clinical Oncology</pub><pmid>31877087</pmid><doi>10.1200/JCO.19.01876</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bleomycin - administration & dosage Chemotherapy, Adjuvant Cisplatin - administration & dosage Etoposide - administration & dosage Humans Male Neoplasm Staging Neoplasms, Germ Cell and Embryonal - drug therapy Neoplasms, Germ Cell and Embryonal - surgery Orchiectomy ORIGINAL REPORTS Progression-Free Survival Retrospective Studies Survival Rate Testicular Neoplasms - drug therapy Testicular Neoplasms - pathology Testicular Neoplasms - surgery Treatment Outcome |
title | Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma |
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