The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy
Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective: To investigate pathologic response rates and s...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | European Urology Open Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666168322006073 |
| _version_ | 1811239447719575552 |
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| author | David D'Andrea Shahrokh F. Shariat Francesco Soria Andrea Mari Laura S. Mertens Ettore Di Trapani Diego M. Carrion Benjamin Pradere Renate Pichler Ronan Filippot Guillaume Grisay Francesco Del Giudice Ekaterina Laukhtina David Paulnsteiner Wojciech Krajewski Sonia Vallet Martina Maggi Ettore De Berardinis Mario Álvarez-Maestro Stephan Brönimann Fabrizio Di Maida Bas W.G. van Rhijn Kees Hendricksen Marco Moschini |
| author_facet | David D'Andrea Shahrokh F. Shariat Francesco Soria Andrea Mari Laura S. Mertens Ettore Di Trapani Diego M. Carrion Benjamin Pradere Renate Pichler Ronan Filippot Guillaume Grisay Francesco Del Giudice Ekaterina Laukhtina David Paulnsteiner Wojciech Krajewski Sonia Vallet Martina Maggi Ettore De Berardinis Mario Álvarez-Maestro Stephan Brönimann Fabrizio Di Maida Bas W.G. van Rhijn Kees Hendricksen Marco Moschini |
| author_sort | David D'Andrea |
| collection | DOAJ |
| description | Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). Conclusions: Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summary: We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non–muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics. |
| first_indexed | 2024-04-12T13:01:35Z |
| format | Article |
| id | doaj.art-566cd181b87c4a359c5886bd710cb412 |
| institution | Directory Open Access Journal |
| issn | 2666-1683 |
| language | English |
| last_indexed | 2024-04-12T13:01:35Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Urology Open Science |
| spelling | doaj.art-566cd181b87c4a359c5886bd710cb4122022-12-22T03:32:09ZengElsevierEuropean Urology Open Science2666-16832022-07-01417480The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant ChemotherapyDavid D'Andrea0Shahrokh F. Shariat1Francesco Soria2Andrea Mari3Laura S. Mertens4Ettore Di Trapani5Diego M. Carrion6Benjamin Pradere7Renate Pichler8Ronan Filippot9Guillaume Grisay10Francesco Del Giudice11Ekaterina Laukhtina12David Paulnsteiner13Wojciech Krajewski14Sonia Vallet15Martina Maggi16Ettore De Berardinis17Mario Álvarez-Maestro18Stephan Brönimann19Fabrizio Di Maida20Bas W.G. van Rhijn21Kees Hendricksen22Marco Moschini23Department of Urology, Medical University of Vienna, Vienna, Austria; Corresponding author. Department of Urology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria. Tel. +43 40 40026150.Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, JordanDepartment of Urology, AOU Città della Salute e della Scienza, Torino School of Medicine, Turin, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Oncologic Minimally Invasive Urology and Andrology Unit, Careggi Hospital, Florence, ItalyDepartment of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The NetherlandsDepartment of Urology, European Institute of Oncology IRCCS, Milan, ItalyDepartment of Urology, Torrejon University Hospital, Madrid, Spain; Francisco de Vitoria University, Madrid, SpainDepartment of Urology, Medical University of Vienna, Vienna, AustriaDepartment of Urology, Medical University Innsbruck, AustriaDepartment of Cancer Medicine, Institut Gustave Roussy, Villejuif, FranceDepartment of Cancer Medicine, Institut Gustave Roussy, Villejuif, FranceDepartment of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, Rome, ItalyDepartment of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech RepublicDepartment of Urology, Medical University of Vienna, Vienna, AustriaDepartment of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wrocław Medical University, Wrocław, PolandDepartment of Internal Medicine II, University Hospital Krems, Karl Landsteiner University of Health Sciences, Krems an der Donau, AustriaDepartment of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, Rome, ItalyDepartment of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, Rome, ItalyDepartment of Urology, Hospital Universitario La Paz, Madrid, SpainDepartment of Urology, Medical University of Vienna, Vienna, AustriaDepartment of Experimental and Clinical Medicine, University of Florence, Oncologic Minimally Invasive Urology and Andrology Unit, Careggi Hospital, Florence, ItalyDepartment of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The NetherlandsDepartment of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The NetherlandsDepartment of Urology, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, ItalyBackground: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). Conclusions: Patients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summary: We investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non–muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.http://www.sciencedirect.com/science/article/pii/S2666168322006073Neoadjuvant chemotherapyBladder cancerResponseSurvivalPrimarySecondary |
| spellingShingle | David D'Andrea Shahrokh F. Shariat Francesco Soria Andrea Mari Laura S. Mertens Ettore Di Trapani Diego M. Carrion Benjamin Pradere Renate Pichler Ronan Filippot Guillaume Grisay Francesco Del Giudice Ekaterina Laukhtina David Paulnsteiner Wojciech Krajewski Sonia Vallet Martina Maggi Ettore De Berardinis Mario Álvarez-Maestro Stephan Brönimann Fabrizio Di Maida Bas W.G. van Rhijn Kees Hendricksen Marco Moschini The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy European Urology Open Science Neoadjuvant chemotherapy Bladder cancer Response Survival Primary Secondary |
| title | The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy |
| title_full | The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy |
| title_fullStr | The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy |
| title_full_unstemmed | The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy |
| title_short | The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy |
| title_sort | impact of primary versus secondary muscle invasive bladder cancer at diagnosis on the response to neoadjuvant chemotherapy |
| topic | Neoadjuvant chemotherapy Bladder cancer Response Survival Primary Secondary |
| url | http://www.sciencedirect.com/science/article/pii/S2666168322006073 |
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