Stefan Kommoss1, Jacobus Pfisterer, Alexander Reuss, Joachim Diebold, Steffen Hauptmann, Christine Schmidt, Andreas du Bois, Dietmar Schmidt, Friedrich Kommoss. 1. *Universitäts-Frauenklinik Tübingen, Germany; †AGO Study Group, Wiesbaden, Germany; §Philipps-Universität Marburg, Koordinierungszentrum für klinische Studien, Marburg, Germany; ∥Luzerner Kantonsspital, Institute of Pathology, Luzern, Switzerland; ¶Institute of Pathology, Dueren, Germany; #Horst-Schmidt-Kliniken (HSK), Wiesbaden, Germany; ††Institute of Pathology, Mannheim, Germany; ‡Gynecologic Oncology Center, Kiel, Germany; and **Department Gynecology & Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
Abstract
BACKGROUND: A significant number of ovarian borderline tumors (BOTs) and metastatic nonovarian primaries are erroneously diagnosed as ovarian carcinomas. If BOTs are misdiagnosed as cancer, patients may not only experience nonbeneficial morbidity but may have to cope with an incorrect diagnosis of cancer for the rest of their lives. In cases of metastatic disease mistaken for an ovarian primary, more adequate therapeutic modalities may be withheld from some patients. Finally, clinical trials may be biased through unintended disregard of histological inclusion criteria. METHODS:Patients were recruited for central pathology review according to a translational subprotocol of a prospectively randomized phase 3 study led by the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group. All original slides were requested, and a specialized central pathology review was performed by experienced gynecopathologists. In cases of clinically relevant diagnostic discrepancies, the pathologist responsible for the original diagnosis was contacted. If a given discrepancy could not be resolved, a panel of experts was involved for clarification. RESULTS:Four hundred fifty-four patients with an original diagnosis of ovarian, tubal, or peritoneal epithelial carcinoma were recruited. In 6.8% (31 patients), a major diagnostic discrepancy of clinical relevance was found. Most frequently (15 patients), serous BOT had been misdiagnosed as invasive cancer. Ovarian metastases constituted the second most frequent misdiagnosis (13 patients). Minor discrepancies not affecting patient treatment were found in 28.2% (128 patients). CONCLUSIONS: Specialized central pathology review could help to avoid overtreatment of patients with BOT and inappropriate treatment of patients with ovarian metastases. The implementation of a specialized case review process may translate into enhanced patient safety in clinical trials of ovarian carcinomas. Furthermore, central pathology review may increase the rigor and ultimately the transferability of clinical research into practice and should therefore become a standard procedure in study protocols evaluating new therapies.
RCT Entities:
BACKGROUND: A significant number of ovarian borderline tumors (BOTs) and metastatic nonovarian primaries are erroneously diagnosed as ovarian carcinomas. If BOTs are misdiagnosed as cancer, patients may not only experience nonbeneficial morbidity but may have to cope with an incorrect diagnosis of cancer for the rest of their lives. In cases of metastatic disease mistaken for an ovarian primary, more adequate therapeutic modalities may be withheld from some patients. Finally, clinical trials may be biased through unintended disregard of histological inclusion criteria. METHODS:Patients were recruited for central pathology review according to a translational subprotocol of a prospectively randomized phase 3 study led by the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group. All original slides were requested, and a specialized central pathology review was performed by experienced gynecopathologists. In cases of clinically relevant diagnostic discrepancies, the pathologist responsible for the original diagnosis was contacted. If a given discrepancy could not be resolved, a panel of experts was involved for clarification. RESULTS: Four hundred fifty-four patients with an original diagnosis of ovarian, tubal, or peritoneal epithelial carcinoma were recruited. In 6.8% (31 patients), a major diagnostic discrepancy of clinical relevance was found. Most frequently (15 patients), serous BOT had been misdiagnosed as invasive cancer. Ovarian metastases constituted the second most frequent misdiagnosis (13 patients). Minor discrepancies not affecting patient treatment were found in 28.2% (128 patients). CONCLUSIONS: Specialized central pathology review could help to avoid overtreatment of patients with BOT and inappropriate treatment of patients with ovarian metastases. The implementation of a specialized case review process may translate into enhanced patient safety in clinical trials of ovarian carcinomas. Furthermore, central pathology review may increase the rigor and ultimately the transferability of clinical research into practice and should therefore become a standard procedure in study protocols evaluating new therapies.
Authors: Martin Köbel; Steve E Kalloger; Sandra Lee; Máire A Duggan; Linda E Kelemen; Leah Prentice; Kimberly R Kalli; Brooke L Fridley; Daniel W Visscher; Gary L Keeney; Robert A Vierkant; Julie M Cunningham; Christine Chow; Roberta B Ness; Kirsten Moysich; Robert Edwards; Francesmary Modugno; Clareann Bunker; Eva L Wozniak; Elizabeth Benjamin; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; C Blake Gilks; David G Huntsman; Susan J Ramus; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-07-23 Impact factor: 4.254
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Authors: Heleen J van Beekhuizen; Mieloe D Freulings; Shatavisha Dasgupta; Folkert J van Kemenade; Patricia C Ewing-Graham; Helena C van Doorn Journal: Virchows Arch Date: 2020-01-09 Impact factor: 4.064
Authors: Mollie E Barnard; Alexander Pyden; Megan S Rice; Miguel Linares; Shelley S Tworoger; Brooke E Howitt; Emily E Meserve; Jonathan L Hecht Journal: Gynecol Oncol Date: 2018-07-09 Impact factor: 5.482
Authors: S Kommoss; F Kommoss; J Diebold; S Lax; D Schmidt; A Staebler; A du Bois; J Pfisterer Journal: Br J Cancer Date: 2016-12-22 Impact factor: 7.640
Authors: Lucas Minig; José Manuel Bosch; Carmen Illueca; Cristina Zorrero; José Miguel Cárdenas-Rebollo; Julia Cruz; Ignacio Romero Journal: Ecancermedicalscience Date: 2019-05-13
Authors: Marina Bagnoli; Ting Yan Shi; Charlie Gourley; Paul Speiser; Alexander Reuss; Hans W Nijman; Carien L Creutzberg; Suzy Scholl; Anastassia Negrouk; Mark F Brady; Kosei Hasegawa; Katsutoshi Oda; Iain A McNeish; Elise C Kohn; Amit M Oza; Helen MacKay; David Millan; Katherine Bennett; Clare Scott; Delia Mezzanzanica Journal: Cells Date: 2019-02-26 Impact factor: 6.600