João Lobo1, Ricardo Leão2, Ad J M Gillis3, Annette van den Berg3, Lynn Anson-Cartwright4, Eshetu G Atenafu5, Kopika Kuhathaas4, Peter Chung6, Aaron Hansen7, Philippe L Bedard7, Michael A S Jewett4, Padraig Warde6, Martin O'Malley8, Joan Sweet9, Leendert H J Looijenga10, Robert J Hamilton11. 1. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPOP), Research Center and Porto Comprehensive Cancer Center (P.CCC), Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal; Department of Pathology and Molecular Immunology, Biomedical Sciences Institute Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal. 2. Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Hospital CUF Coimbra, Department of Urology, Hospital de Braga, Braga, Portugal; Departments of Surgery (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. 3. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. 4. Departments of Surgery (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. 5. Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 6. Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 7. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 8. Department of Medical Imaging, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 9. Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. 10. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. Electronic address: l.looijenga@prinsesmaximacentrum.nl. 11. Departments of Surgery (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address: rob.hamilton@uhn.ca.
Abstract
BACKGROUND: Optimal management of clinical stage I (CSI) testicular cancer is controversial due to lack of robust prognostic factors; miRNA-371a-3p holds promise as a biomarker, although its clinical utility for identifying patients at risk of relapse is unknown. OBJECTIVE: To explore the association between serum miR-371a-3p and CSI surveillance relapse. DESIGN, SETTING, AND PARTICIPANTS: Serial banked sera from 151 CSI (101 seminomas and 50 nonseminomatous germ cell tumors [NSGCTs]) samples from our Princess Margaret active surveillance cohort were tested. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the ampTSmiR test, miR-371a-3p was assayed. Multivariate logistic regression was used to assess the association between postorchiectomy miRNA and relapse. RESULTS AND LIMITATIONS: Thirty-four (23%) patients relapsed. There was no association between postorchiectomy miR-371a-3p (2.43 vs 2.74, p = 0.31) or percent decline from before to after orchiectomy (95.8% vs 93.1%, p = 0.14) and relapse. After adjustment for clinical prognostic factors, there remained no association between postorchiectomy miR-371a-3p and relapse (seminoma: odds ratio [OR] 1.33, 95% confidence interval [CI] 0.87-2.02, p = 0.18; NSGCT: OR 0.45, 95% CI 0.21-1.00, p = 0.05). Postorchiectomy miR-371a-3p levels rose as the date of miRNA assessment approached relapse. At relapse, serum markers alpha-fetoprotein and human chorionic gonadotropin were normal in 62%; yet, miR-371a-3p was elevated in 32/34 (94.1%). The magnitude of miR-371a-3p elevation at relapse correlated with disease burden (N1/M0 122.5 vs N2-N3/M0: 521.1; p = 0.05). Limitations include small numbers of relapses and variable time points of serum collection. CONCLUSIONS: In our cohort of CSI testis cancer patients on surveillance, postorchiectomy miR-371a-3p levels were not associated with relapse, suggesting that miR-371a-3p may not be a useful biomarker for guiding adjuvant therapy. Our data suggest that miR-371a-3p holds potential as an early relapse marker and warrants a prospective study, as this may allow a window for less morbid relapse therapy. PATIENT SUMMARY: The promising novel blood biomarker for testis cancer miR-371a-3p may not provide information at testicle removal, but serial monitoring may lead to earlier detection of relapse.
BACKGROUND: Optimal management of clinical stage I (CSI) testicular cancer is controversial due to lack of robust prognostic factors; miRNA-371a-3p holds promise as a biomarker, although its clinical utility for identifying patients at risk of relapse is unknown. OBJECTIVE: To explore the association between serum miR-371a-3p and CSI surveillance relapse. DESIGN, SETTING, AND PARTICIPANTS: Serial banked sera from 151 CSI (101 seminomas and 50 nonseminomatous germ cell tumors [NSGCTs]) samples from our Princess Margaret active surveillance cohort were tested. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the ampTSmiR test, miR-371a-3p was assayed. Multivariate logistic regression was used to assess the association between postorchiectomy miRNA and relapse. RESULTS AND LIMITATIONS: Thirty-four (23%) patients relapsed. There was no association between postorchiectomy miR-371a-3p (2.43 vs 2.74, p = 0.31) or percent decline from before to after orchiectomy (95.8% vs 93.1%, p = 0.14) and relapse. After adjustment for clinical prognostic factors, there remained no association between postorchiectomy miR-371a-3p and relapse (seminoma: odds ratio [OR] 1.33, 95% confidence interval [CI] 0.87-2.02, p = 0.18; NSGCT: OR 0.45, 95% CI 0.21-1.00, p = 0.05). Postorchiectomy miR-371a-3p levels rose as the date of miRNA assessment approached relapse. At relapse, serum markers alpha-fetoprotein and human chorionic gonadotropin were normal in 62%; yet, miR-371a-3p was elevated in 32/34 (94.1%). The magnitude of miR-371a-3p elevation at relapse correlated with disease burden (N1/M0 122.5 vs N2-N3/M0: 521.1; p = 0.05). Limitations include small numbers of relapses and variable time points of serum collection. CONCLUSIONS: In our cohort of CSI testis cancer patients on surveillance, postorchiectomy miR-371a-3p levels were not associated with relapse, suggesting that miR-371a-3p may not be a useful biomarker for guiding adjuvant therapy. Our data suggest that miR-371a-3p holds potential as an early relapse marker and warrants a prospective study, as this may allow a window for less morbid relapse therapy. PATIENT SUMMARY: The promising novel blood biomarker for testis cancer miR-371a-3p may not provide information at testicle removal, but serial monitoring may lead to earlier detection of relapse.
Authors: John T Lafin; Matthew J Murray; Nicholas Coleman; A Lindsay Frazier; James F Amatruda; Aditya Bagrodia Journal: Mol Diagn Ther Date: 2021-04-24 Impact factor: 4.074
Authors: Friedemann Zengerling; Dirk Beyersdorff; Jonas Busch; Julia Heinzelbecker; David Pfister; Christian Ruf; Christian Winter; Peter Albers; Sabine Kliesch; Stefanie Schmidt Journal: World J Urol Date: 2022-07-29 Impact factor: 3.661
Authors: Christian D Fankhauser; Ailsa J Christiansen; Christian Rothermundt; Richard Cathomas; Marian S Wettstein; Nico C Grossmann; Josias B Grogg; Arnoud J Templeton; Anita Hirschi-Blickenstorfer; Anja Lorch; Silke Gillessen; Holger Moch; Joerg Beyer; Thomas Hermanns Journal: Br J Cancer Date: 2021-12-15 Impact factor: 9.075
Authors: Peter J Gariscsak; Lynn Anson-Cartwright; Eshetu G Atenafu; Di Maria Jiang; Peter Chung; Philippe Bedard; Padraig Warde; Martin O'Malley; Joan Sweet; Rachel M Glicksman; Robert J Hamilton Journal: Eur Urol Open Sci Date: 2022-04-27
Authors: José Pedro Sequeira; João Lobo; Vera Constâncio; Tiago Brito-Rocha; Carina Carvalho-Maia; Isaac Braga; Joaquina Maurício; Rui Henrique; Carmen Jerónimo Journal: Front Oncol Date: 2022-06-10 Impact factor: 5.738
Authors: Ernest Kaufmann; Luca Antonelli; Peter Albers; Clint Cary; Silke Gillessen Sommer; Axel Heidenreich; Christoph Oing; Jan Oldenburg; Phillip Martin Pierorazio; Andrew J Stephenson; Christian Daniel Fankhauser Journal: Eur Urol Open Sci Date: 2022-09-07