Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

PORTEC Study Grp

doi:10.1093/annonc/mdx753

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

PORTEC Study Grp

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Abstract

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m(2) in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m(2)). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.

Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (j).

Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (j = 0.72), lymph-vascular space invasion (j = 0.72) and histological grade (j = 0.70).

Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over-or undertreatment, especially when treatment modalities with substantial toxicity are involved.

This study is registered with ISRCTN (ISRCTN14387080, www. controlled-trials. com) and with ClinicalTrials. gov (NCT00411138).

Original language	English
Pages (from-to)	424-430
Number of pages	7
Journal	Annals of Oncology
Volume	29
Issue number	2
DOIs	https://doi.org/10.1093/annonc/mdx753
Publication status	Published - Feb-2018

Keywords

endometrial carcinoma
randomised trial
radiation therapy
chemotherapy
pathology review
high risk
EXTERNAL-BEAM RADIOTHERAPY
RADIATION-THERAPY
POSTOPERATIVE RADIOTHERAPY
INTEROBSERVER VARIABILITY
GRADING SYSTEMS
OPEN-LABEL
STAGE-I
CARCINOMA
REPRODUCIBILITY
DIAGNOSIS

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Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancerFinal publisher's version, 311 KBLicence: CC BY

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@article{3733221930964f91b9bf007050f7f370,

title = "Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer",

abstract = "Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m(2) in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m(2)). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (j).Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (j = 0.72), lymph-vascular space invasion (j = 0.72) and histological grade (j = 0.70).Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over-or undertreatment, especially when treatment modalities with substantial toxicity are involved.This study is registered with ISRCTN (ISRCTN14387080, www. controlled-trials. com) and with ClinicalTrials. gov (NCT00411138).",

keywords = "endometrial carcinoma, randomised trial, radiation therapy, chemotherapy, pathology review, high risk, EXTERNAL-BEAM RADIOTHERAPY, RADIATION-THERAPY, POSTOPERATIVE RADIOTHERAPY, INTEROBSERVER VARIABILITY, GRADING SYSTEMS, OPEN-LABEL, STAGE-I, CARCINOMA, REPRODUCIBILITY, DIAGNOSIS",

author = "{PORTEC Study Grp} and {de Boer}, {S. M.} and Wortman, {B. G.} and T. Bosse and Powell, {M. E.} and N. Singh and H. Hollema and G. Wilson and Chowdhury, {M. N.} and L. Mileshkin and J. Pyman and D. Katsaros and S. Carinelli and A. Fyles and McLachlin, {C. M.} and C. Haie-Meder and P. Duvillard and Nout, {R. A.} and Verhoeven-Adema, {K. W.} and H. Putter and Creutzberg, {C. L.} and Smit, {V. T. H. B. M.}",

year = "2018",

month = feb,

doi = "10.1093/annonc/mdx753",

language = "English",

volume = "29",

pages = "424--430",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

AU - PORTEC Study Grp

AU - de Boer, S. M.

AU - Wortman, B. G.

AU - Bosse, T.

AU - Powell, M. E.

AU - Singh, N.

AU - Hollema, H.

AU - Wilson, G.

AU - Chowdhury, M. N.

AU - Mileshkin, L.

AU - Pyman, J.

AU - Katsaros, D.

AU - Carinelli, S.

AU - Fyles, A.

AU - McLachlin, C. M.

AU - Haie-Meder, C.

AU - Duvillard, P.

AU - Nout, R. A.

AU - Verhoeven-Adema, K. W.

AU - Putter, H.

AU - Creutzberg, C. L.

AU - Smit, V. T. H. B. M.

PY - 2018/2

Y1 - 2018/2

N2 - Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m(2) in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m(2)). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (j).Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (j = 0.72), lymph-vascular space invasion (j = 0.72) and histological grade (j = 0.70).Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over-or undertreatment, especially when treatment modalities with substantial toxicity are involved.This study is registered with ISRCTN (ISRCTN14387080, www. controlled-trials. com) and with ClinicalTrials. gov (NCT00411138).

AB - Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m(2) in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m(2)). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation.Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (j).Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (j = 0.72), lymph-vascular space invasion (j = 0.72) and histological grade (j = 0.70).Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over-or undertreatment, especially when treatment modalities with substantial toxicity are involved.This study is registered with ISRCTN (ISRCTN14387080, www. controlled-trials. com) and with ClinicalTrials. gov (NCT00411138).

KW - endometrial carcinoma

KW - randomised trial

KW - radiation therapy

KW - chemotherapy

KW - pathology review

KW - high risk

KW - EXTERNAL-BEAM RADIOTHERAPY

KW - RADIATION-THERAPY

KW - POSTOPERATIVE RADIOTHERAPY

KW - INTEROBSERVER VARIABILITY

KW - GRADING SYSTEMS

KW - OPEN-LABEL

KW - STAGE-I

KW - CARCINOMA

KW - REPRODUCIBILITY

KW - DIAGNOSIS

U2 - 10.1093/annonc/mdx753

DO - 10.1093/annonc/mdx753

M3 - Article

SN - 0923-7534

VL - 29

SP - 424

EP - 430

JO - Annals of Oncology

JF - Annals of Oncology

IS - 2

ER -

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer

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Keywords

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