Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial
Abstract Background The recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20–40% of patients experience a complete pathological response (pCR) in the RC specimen and these patient...
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| Format: | Article |
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BMC
2021-10-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-021-08840-2 |
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| author | F. J. Hinsenveld B. J. Noordman J. L. Boormans J. Voortman G. J. L. H. van Leenders S. L. van der Pas S. C. van Beek D. E. Oprea-Lager A. N. Vis |
| author_facet | F. J. Hinsenveld B. J. Noordman J. L. Boormans J. Voortman G. J. L. H. van Leenders S. L. van der Pas S. C. van Beek D. E. Oprea-Lager A. N. Vis |
| author_sort | F. J. Hinsenveld |
| collection | DOAJ |
| description | Abstract Background The recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20–40% of patients experience a complete pathological response (pCR) in the RC specimen and these patients have excellent long-term overall survival. Subject to debate is, however, whether patients with a pCR to NAC benefit from RC, which is a major surgical procedure with substantial morbidity, and if these patients might be candidates for close surveillance instead. However, currently it is not possible to accurately identify patients with a pCR to NAC in whom RC might be withheld. The objective of this study is to assess whether pathological response in the RC specimen after NAC can be predicted based on clinical, radiological, and histological variables and on a wide set of molecular biomarkers assessed in tissue, blood and urine. Methods This is a multicentre, prospective cohort study, including patients with cT2a-T4a N0-N1 M0 urothelial cell MIBC who are scheduled to undergo cisplatin-based NAC followed by RC. Prior to start of therapy, a 2-Deoxy-2-[18F] fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is performed. Response to NAC is evaluated by CT-scan. Blood and urine, including cytology, are prospectively collected for biomarker analyses before and after NAC. Immediately before RC, participants undergo cystoscopy with bimanual examination and a re-staging transurethral resection (TUR) of all visible cancerous lesions or with biopsies from scar tissue. Subsequently, RC is performed in all patients. Tissue from the diagnostic TUR, the re-staging TUR, and the RC specimen is examined for the presence of urothelial cancer carcinoma and DNA and RNA is isolated for molecular analysis. The primary endpoint is the pathological stage (ypTN) in the RC and ePLND specimen and its association with clinical response. Discussion If the PRE-PREVENCYS trial shows that the absence of residual disease after NAC in patients with MIBC is accurately predicted, a randomized controlled trial is scheduled comparing the overall survival of NAC plus RC versus NAC followed by close surveillance for patients with a clinically complete response (PREVENCYS trial). Trial registration Netherlands Trial Register: NL8678; Registered 20 May 2020 https://www.trialregister.nl/trial/8678 |
| first_indexed | 2024-12-21T00:53:04Z |
| format | Article |
| id | doaj.art-6d35e33e092449ec8aaa323ef679abd9 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T00:53:04Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj.art-6d35e33e092449ec8aaa323ef679abd92022-12-21T19:21:22ZengBMCBMC Cancer1471-24072021-10-0121111110.1186/s12885-021-08840-2Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trialF. J. Hinsenveld0B. J. Noordman1J. L. Boormans2J. Voortman3G. J. L. H. van Leenders4S. L. van der Pas5S. C. van Beek6D. E. Oprea-Lager7A. N. Vis8Department of Urology, Amsterdam University Medical Centers, VU UniversityDepartment of Surgery, Erasmus MC, University Medical Center RotterdamDepartment of Urology, Erasmus MC, University Medical Center RotterdamDepartment of Medical Oncology, Amsterdam University Medical Centers, VU UniversityDepartment of pathology, Erasmus MC, University Medical Center RotterdamDepartment of Epidemiology and Biostatistics, Amsterdam University Medical Centers, VU UniversityDepartment of Surgery, Erasmus MC, University Medical Center RotterdamDepartment of Radiology & Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Centers, VU UniversityDepartment of Urology, Amsterdam University Medical Centers, VU UniversityAbstract Background The recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20–40% of patients experience a complete pathological response (pCR) in the RC specimen and these patients have excellent long-term overall survival. Subject to debate is, however, whether patients with a pCR to NAC benefit from RC, which is a major surgical procedure with substantial morbidity, and if these patients might be candidates for close surveillance instead. However, currently it is not possible to accurately identify patients with a pCR to NAC in whom RC might be withheld. The objective of this study is to assess whether pathological response in the RC specimen after NAC can be predicted based on clinical, radiological, and histological variables and on a wide set of molecular biomarkers assessed in tissue, blood and urine. Methods This is a multicentre, prospective cohort study, including patients with cT2a-T4a N0-N1 M0 urothelial cell MIBC who are scheduled to undergo cisplatin-based NAC followed by RC. Prior to start of therapy, a 2-Deoxy-2-[18F] fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is performed. Response to NAC is evaluated by CT-scan. Blood and urine, including cytology, are prospectively collected for biomarker analyses before and after NAC. Immediately before RC, participants undergo cystoscopy with bimanual examination and a re-staging transurethral resection (TUR) of all visible cancerous lesions or with biopsies from scar tissue. Subsequently, RC is performed in all patients. Tissue from the diagnostic TUR, the re-staging TUR, and the RC specimen is examined for the presence of urothelial cancer carcinoma and DNA and RNA is isolated for molecular analysis. The primary endpoint is the pathological stage (ypTN) in the RC and ePLND specimen and its association with clinical response. Discussion If the PRE-PREVENCYS trial shows that the absence of residual disease after NAC in patients with MIBC is accurately predicted, a randomized controlled trial is scheduled comparing the overall survival of NAC plus RC versus NAC followed by close surveillance for patients with a clinically complete response (PREVENCYS trial). Trial registration Netherlands Trial Register: NL8678; Registered 20 May 2020 https://www.trialregister.nl/trial/8678https://doi.org/10.1186/s12885-021-08840-2Bladder cancerCancer biomarkersCystectomyNeoadjuvant chemotherapyResidual tumourBladder-sparing |
| spellingShingle | F. J. Hinsenveld B. J. Noordman J. L. Boormans J. Voortman G. J. L. H. van Leenders S. L. van der Pas S. C. van Beek D. E. Oprea-Lager A. N. Vis Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial BMC Cancer Bladder cancer Cancer biomarkers Cystectomy Neoadjuvant chemotherapy Residual tumour Bladder-sparing |
| title | Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial |
| title_full | Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial |
| title_fullStr | Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial |
| title_full_unstemmed | Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial |
| title_short | Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial |
| title_sort | prediction of pathological response following neoadjuvant chemotherapy in patients with muscle invasive bladder cancer the pre prevencys trial |
| topic | Bladder cancer Cancer biomarkers Cystectomy Neoadjuvant chemotherapy Residual tumour Bladder-sparing |
| url | https://doi.org/10.1186/s12885-021-08840-2 |
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