Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy

Paul A Cohen; Yee Leung; Lyndal Anderson; Rachael van der Griend; Paola Chivers; Sanela Bilic; Sophie Bittinger; Alison Brand; Max K Bulsara; Jim Codde; Lois Eva; Louise Farrell; Dianne Harker; Unine Herbst; Stephanie Jeffares; Diane Loh; Orla McNally; Ganendra Raj Mohan; Tarryn Nicholson; Aime Powell; Stuart G Salfinger; Bryony Simcock; Colin Stewart; Julie Silvers; Martin R Stockler; Peter Sykes; Pennie Stoyles; Adeline Tan; Ai Ling Tan; C David H Wrede

doi:10.1016/j.ygyno.2020.09.053

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy

Gynecol Oncol. 2020 Dec;159(3):623-629. doi: 10.1016/j.ygyno.2020.09.053. Epub 2020 Oct 5.

Authors

Paul A Cohen¹, Yee Leung², Lyndal Anderson³, Rachael van der Griend⁴, Paola Chivers⁵, Sanela Bilic⁶, Sophie Bittinger⁷, Alison Brand⁸, Max K Bulsara⁹, Jim Codde¹⁰, Lois Eva¹¹, Louise Farrell¹², Dianne Harker¹³, Unine Herbst¹⁴, Stephanie Jeffares⁶, Diane Loh¹⁵, Orla McNally¹⁶, Ganendra Raj Mohan¹⁷, Tarryn Nicholson¹⁸, Aime Powell¹⁰, Stuart G Salfinger⁶, Bryony Simcock¹⁹, Colin Stewart²⁰, Julie Silvers⁷, Martin R Stockler²¹, Peter Sykes¹⁹, Pennie Stoyles²², Adeline Tan²³, Ai Ling Tan²⁴, C David H Wrede¹⁶

Affiliations

¹ Division of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia; Dept of Gynaecological Oncology, St John of God Hospital, Subiaco, Western Australia, Australia; Dept of Gynaecological Oncology, King Edward Memorial Hospital, Subiaco, Western Australia, Australia; Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia. Electronic address: [email protected].
² Division of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia; Dept of Gynaecological Oncology, King Edward Memorial Hospital, Subiaco, Western Australia, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
³ Sydney Medical School, The University of Sydney, New South Wales, Australia; School of Medicine, Western Sydney University, Penrith South, New South Wales, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
⁴ Department of Anatomical Pathology, Canterbury Health Laboratories, Christchurch, New Zealand.
⁵ Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia; Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia.
⁶ Dept of Gynaecological Oncology, St John of God Hospital, Subiaco, Western Australia, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
⁷ Oncology and Dysplasia Unit, The Royal Women's Hospital, Melbourne, Victoria, Australia.
⁸ Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia; Discipline of Obstetrics and Gynaecology, University of Sydney, Sydney, New South Wales, Australia.
⁹ Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia.
¹⁰ Institute for Health Research, University of Notre Dame Australia, Fremantle, Western Australia, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
¹¹ Dept of Gynaecological Oncology, National Women's Health, Auckland City Hospital, Auckland, New Zealand; Department of Gynaecological Oncology, University of Auckland, Auckland, New Zealand; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
¹² Dept of Gynaecological Oncology, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.
¹³ Department of Obstetrics and Gynaecology, Univeristy of Otago, Christchurch, New Zealand.
¹⁴ Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
¹⁵ Division of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia; Dept of Gynaecological Oncology, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.
¹⁶ Oncology and Dysplasia Unit, The Royal Women's Hospital, Melbourne, Victoria, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
¹⁷ Dept of Gynaecological Oncology, St John of God Hospital, Subiaco, Western Australia, Australia; Dept of Gynaecological Oncology, King Edward Memorial Hospital, Subiaco, Western Australia, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
¹⁸ Dept of Gynaecological Oncology, National Women's Health, Auckland City Hospital, Auckland, New Zealand.
¹⁹ Department of Obstetrics and Gynaecology, Univeristy of Otago, Christchurch, New Zealand; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia; Christchurch Womens Hospital, Christchurch, New Zealand.
²⁰ Division of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia; PathWest, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.
²¹ NHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
²² Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.
²³ Clinipath Pathology, Osborne Park, Western Australia, Australia.
²⁴ Dept of Gynaecological Oncology, National Women's Health, Auckland City Hospital, Auckland, New Zealand; Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.

PMID: 33032824
DOI: 10.1016/j.ygyno.2020.09.053

Abstract

Objective: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC).

Methods: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat.

Results: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65).

Conclusions: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

Keywords: AIS; Cervical adenocarcinoma in situ; Cervical dysplasia; Cold knife cone biopsy; LLETZ; Loop electrosurgical excision.

Publication types

Clinical Trial, Phase II
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma in Situ / pathology
Adenocarcinoma in Situ / surgery*
Adult
Biopsy / adverse effects
Biopsy / instrumentation
Biopsy / methods
Cervix Uteri / pathology
Cervix Uteri / surgery
Electrosurgery / adverse effects*
Electrosurgery / instrumentation
Electrosurgery / methods
Female
Humans
Margins of Excision
Pilot Projects
Postoperative Complications / diagnosis
Postoperative Complications / epidemiology*
Postoperative Complications / etiology
Severity of Illness Index
Uterine Cervical Neoplasms / pathology
Uterine Cervical Neoplasms / surgery*