The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis
•Patients with Lymph node positive disease after radical cystectomy with extended lymphadenectomy fare worse than patients with lymph node negative disease.•Patients with pN1 disease didn't differ in long-term survival outcomes from patients with pN2-3 disease. Patients with both node positive...
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| creator | Ben-David, Reuben Lidagoster, Sarah Geduldig, Jack Kolanukuduru, Kaushik P. Elkun, Yuval Tillu, Neeraja Cumarasamy, Shivaram Rich, Jordan M. Almoflihi, Mohammed Attalla, Kyrollis Mehrazin, Reza Wiklund, Peter Sfakianos, John P. |
| description | •Patients with Lymph node positive disease after radical cystectomy with extended lymphadenectomy fare worse than patients with lymph node negative disease.•Patients with pN1 disease didn't differ in long-term survival outcomes from patients with pN2-3 disease. Patients with both node positive disease and locally advanced disease (≥pT3) had the worst survival outcomes.•Precystectomy and postcystectomy (minimal residual disease window) undetectable ctDNA status were informative of recurrence-free survival regardless of nodal status.•Patients with undetectable ctDNA status and positive lymph node disease may benefit from treatment de-escalation. Detectable precystectomy ctDNA status may be used for selecting patients to extended lymph node dissection templates.
Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.
Patients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted.
Included were 458 patients with a median age of 69 (IQR 63–76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18–5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55–3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11–2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32–11.4], P = 0.014), detectable ctDNA sta |
| doi_str_mv | 10.1016/j.urolonc.2024.08.006 |
| format | Article |
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Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.
Patients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted.
Included were 458 patients with a median age of 69 (IQR 63–76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18–5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55–3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11–2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32–11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12–7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43–12.3], P = 0.009) were predictive of disease relapse.
Patients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.</description><identifier>ISSN: 1078-1439</identifier><identifier>ISSN: 1873-2496</identifier><identifier>EISSN: 1873-2496</identifier><identifier>DOI: 10.1016/j.urolonc.2024.08.006</identifier><identifier>PMID: 39277526</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Circulating tumor DNA ; Circulating Tumor DNA - blood ; Circulating Tumor DNA - genetics ; Cystectomy - methods ; Female ; Humans ; Lymph Node Excision - methods ; Lymphatic Metastasis ; Male ; Middle Aged ; Nonmuscle invasive bladder neoplasms ; Prognosis ; Robotic Surgical Procedures - methods ; Tumor biomarkers ; Urinary bladder neoplasms ; Urinary Bladder Neoplasms - blood ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - pathology ; Urinary Bladder Neoplasms - surgery</subject><ispartof>Urologic oncology, 2025-01, Vol.43 (1), p.66.e9-66.e17</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c243t-45e06d3cd741c5da22bec390330b12394fb17c01e67d164b46e06cecfdb806ef3</cites><orcidid>0000-0001-7946-7145</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1078143924005763$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39277526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ben-David, Reuben</creatorcontrib><creatorcontrib>Lidagoster, Sarah</creatorcontrib><creatorcontrib>Geduldig, Jack</creatorcontrib><creatorcontrib>Kolanukuduru, Kaushik P.</creatorcontrib><creatorcontrib>Elkun, Yuval</creatorcontrib><creatorcontrib>Tillu, Neeraja</creatorcontrib><creatorcontrib>Cumarasamy, Shivaram</creatorcontrib><creatorcontrib>Rich, Jordan M.</creatorcontrib><creatorcontrib>Almoflihi, Mohammed</creatorcontrib><creatorcontrib>Attalla, Kyrollis</creatorcontrib><creatorcontrib>Mehrazin, Reza</creatorcontrib><creatorcontrib>Wiklund, Peter</creatorcontrib><creatorcontrib>Sfakianos, John P.</creatorcontrib><title>The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis</title><title>Urologic oncology</title><addtitle>Urol Oncol</addtitle><description>•Patients with Lymph node positive disease after radical cystectomy with extended lymphadenectomy fare worse than patients with lymph node negative disease.•Patients with pN1 disease didn't differ in long-term survival outcomes from patients with pN2-3 disease. Patients with both node positive disease and locally advanced disease (≥pT3) had the worst survival outcomes.•Precystectomy and postcystectomy (minimal residual disease window) undetectable ctDNA status were informative of recurrence-free survival regardless of nodal status.•Patients with undetectable ctDNA status and positive lymph node disease may benefit from treatment de-escalation. Detectable precystectomy ctDNA status may be used for selecting patients to extended lymph node dissection templates.
Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.
Patients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted.
Included were 458 patients with a median age of 69 (IQR 63–76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18–5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55–3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11–2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32–11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12–7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43–12.3], P = 0.009) were predictive of disease relapse.
Patients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.</description><subject>Aged</subject><subject>Circulating tumor DNA</subject><subject>Circulating Tumor DNA - blood</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Cystectomy - methods</subject><subject>Female</subject><subject>Humans</subject><subject>Lymph Node Excision - methods</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nonmuscle invasive bladder neoplasms</subject><subject>Prognosis</subject><subject>Robotic Surgical Procedures - methods</subject><subject>Tumor biomarkers</subject><subject>Urinary bladder neoplasms</subject><subject>Urinary Bladder Neoplasms - blood</subject><subject>Urinary Bladder Neoplasms - genetics</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urinary Bladder Neoplasms - surgery</subject><issn>1078-1439</issn><issn>1873-2496</issn><issn>1873-2496</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxiMEoqXwCKA5cslix9784YJWBVqkCi7lbDnjya5XiR1sp1XehwfF1S5cOXls_Wa-8fcVxVvONpzx-sNxswQ_eoebilVyw9oNY_Wz4pK3jSgr2dXPc82atuRSdBfFqxiPjHHZcv6yuBBd1TTbqr4sft8fCObg987HZBGi3Ts7WNQOCfwAaAMuo07W7SEtkw_w-fsOrIM5v5FLER5tOsDso032gWBcp_kAzhsCYyPpSKCHRAGC730WKHWMNiYyELTJMiPgmq-Y_LR-hB2gd4mm2QcdVtBOj2vGXxcvBj1GenM-r4qfX7_cX9-Wdz9uvl3v7kqspEil3BKrjUDTSI5bo6uqJxQdE4L1vBKdHHreIONUN4bXspd15pFwMH3LahrEVfH-NDcb8muhmNRkI9I4akd-iUpwtpUdyx5mdHtCMfgYAw1qDnbKSyvO1FNA6qjOAamngBRrVQ4o9707Syz9ROZf199EMvDpBFD-6IOloCJmo5GMDdkmZbz9j8QffsupgQ</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Ben-David, Reuben</creator><creator>Lidagoster, Sarah</creator><creator>Geduldig, Jack</creator><creator>Kolanukuduru, Kaushik P.</creator><creator>Elkun, Yuval</creator><creator>Tillu, Neeraja</creator><creator>Cumarasamy, Shivaram</creator><creator>Rich, Jordan M.</creator><creator>Almoflihi, Mohammed</creator><creator>Attalla, Kyrollis</creator><creator>Mehrazin, Reza</creator><creator>Wiklund, Peter</creator><creator>Sfakianos, John P.</creator><general>Elsevier Inc</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>7X8</scope><orcidid>https://orcid.org/0000-0001-7946-7145</orcidid></search><sort><creationdate>202501</creationdate><title>The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis</title><author>Ben-David, Reuben ; Lidagoster, Sarah ; Geduldig, Jack ; Kolanukuduru, Kaushik P. ; Elkun, Yuval ; Tillu, Neeraja ; Cumarasamy, Shivaram ; Rich, Jordan M. ; Almoflihi, Mohammed ; Attalla, Kyrollis ; Mehrazin, Reza ; Wiklund, Peter ; Sfakianos, John P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c243t-45e06d3cd741c5da22bec390330b12394fb17c01e67d164b46e06cecfdb806ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Aged</topic><topic>Circulating tumor DNA</topic><topic>Circulating Tumor DNA - blood</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Cystectomy - methods</topic><topic>Female</topic><topic>Humans</topic><topic>Lymph Node Excision - methods</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nonmuscle invasive bladder neoplasms</topic><topic>Prognosis</topic><topic>Robotic Surgical Procedures - methods</topic><topic>Tumor biomarkers</topic><topic>Urinary bladder neoplasms</topic><topic>Urinary Bladder Neoplasms - blood</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urinary Bladder Neoplasms - surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ben-David, Reuben</creatorcontrib><creatorcontrib>Lidagoster, Sarah</creatorcontrib><creatorcontrib>Geduldig, Jack</creatorcontrib><creatorcontrib>Kolanukuduru, Kaushik P.</creatorcontrib><creatorcontrib>Elkun, Yuval</creatorcontrib><creatorcontrib>Tillu, Neeraja</creatorcontrib><creatorcontrib>Cumarasamy, Shivaram</creatorcontrib><creatorcontrib>Rich, Jordan M.</creatorcontrib><creatorcontrib>Almoflihi, Mohammed</creatorcontrib><creatorcontrib>Attalla, Kyrollis</creatorcontrib><creatorcontrib>Mehrazin, Reza</creatorcontrib><creatorcontrib>Wiklund, Peter</creatorcontrib><creatorcontrib>Sfakianos, John P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Urologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ben-David, Reuben</au><au>Lidagoster, Sarah</au><au>Geduldig, Jack</au><au>Kolanukuduru, Kaushik P.</au><au>Elkun, Yuval</au><au>Tillu, Neeraja</au><au>Cumarasamy, Shivaram</au><au>Rich, Jordan M.</au><au>Almoflihi, Mohammed</au><au>Attalla, Kyrollis</au><au>Mehrazin, Reza</au><au>Wiklund, Peter</au><au>Sfakianos, John P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis</atitle><jtitle>Urologic oncology</jtitle><addtitle>Urol Oncol</addtitle><date>2025-01</date><risdate>2025</risdate><volume>43</volume><issue>1</issue><spage>66.e9</spage><epage>66.e17</epage><pages>66.e9-66.e17</pages><issn>1078-1439</issn><issn>1873-2496</issn><eissn>1873-2496</eissn><abstract>•Patients with Lymph node positive disease after radical cystectomy with extended lymphadenectomy fare worse than patients with lymph node negative disease.•Patients with pN1 disease didn't differ in long-term survival outcomes from patients with pN2-3 disease. Patients with both node positive disease and locally advanced disease (≥pT3) had the worst survival outcomes.•Precystectomy and postcystectomy (minimal residual disease window) undetectable ctDNA status were informative of recurrence-free survival regardless of nodal status.•Patients with undetectable ctDNA status and positive lymph node disease may benefit from treatment de-escalation. Detectable precystectomy ctDNA status may be used for selecting patients to extended lymph node dissection templates.
Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.
Patients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted.
Included were 458 patients with a median age of 69 (IQR 63–76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18–5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55–3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11–2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32–11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12–7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43–12.3], P = 0.009) were predictive of disease relapse.
Patients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39277526</pmid><doi>10.1016/j.urolonc.2024.08.006</doi><orcidid>https://orcid.org/0000-0001-7946-7145</orcidid></addata></record> |
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| subjects | Aged Circulating tumor DNA Circulating Tumor DNA - blood Circulating Tumor DNA - genetics Cystectomy - methods Female Humans Lymph Node Excision - methods Lymphatic Metastasis Male Middle Aged Nonmuscle invasive bladder neoplasms Prognosis Robotic Surgical Procedures - methods Tumor biomarkers Urinary bladder neoplasms Urinary Bladder Neoplasms - blood Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology Urinary Bladder Neoplasms - surgery |
| title | The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis |
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