A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice

Abstract

Background Adult guidelines recommend BEP (bleomycin, etoposide, cisplatin) for all ovarian germ cell tumours, causing debilitating toxicities in young patients who will survive long term. Paediatricians successfully reduce toxicities by using lower bleomycin doses and substituting carboplatin for cisplatin, while testicular and paediatric immature teratomas (ITs) are safely managed with surgery alone. Aim The aim was to determine whether reduced-toxicity treatment could rationally be extended to patients older than 18 years. Methods Multicentre cohort study was carried out in four large UK cancer centres over 12 years. Results One hundred thirty-eight patients were enrolled. Overall survival was 93%, and event-free survival (EFS) was 72%. Neoadjuvant/adjuvant chemotherapy (82% BEP) caused 27 potentially chronic toxicities, and one patient subsequently died from acute lymphoblastic leukaemia. There was no difference in histology, stage or grade in patients ≤/>18 years, and EFS was not different in these age groups (≤18:28% and >18:28%; log-rank P = 0.96). Histological subtype powerfully predicted EFS (log-rank P = 4.9 × 10 −7 ). Neoadjuvant/adjuvant chemotherapy reduced future relapse/progression in dysgerminoma (n = 37, chemo:0% vs. no chemo:20%), yolk sac tumour (n = 23, 26.3% vs.75%) and mixed germ cell tumour (n = 32, 40%vs.70%) but not in IT (n = 42, 33% vs.15%). Additionally, we observed no radiological responses to chemotherapy in ITs, pathological IT grade did not predict EFS (univariate hazard ratio 0.82, 95% confidence interval: 0.57–1.19, P = 0.94) and there were no deaths in this subtype. Conclusion Survival was excellent but chemotherapy toxicities were severe, implying significant overtreatment. Our data support the extension of reduced-toxicity, paediatric regimens to adults. Our practice-changing findings that IT was chemotherapy resistant and pathological grade uninformative strongly endorse exclusive surgical management of ovarian ITs at all ages.

Ovarian germ cell tumour classification: views from the testis

“…Some of the authors of this review have recently published a retrospective series of ovarian germ cell tumours, concentrating on a number of different factors . First, on review, even small areas of other elements meant assignation to a mixed germ cell tumour rather than a pure IT.…”

“…Event‐free survival according to ( A ) FIGO stage, ( B ) histological OvGCT subtype, ( C ) patient age at diagnosis and ( D ) grade of immature teratoma. OvGCT, ovarian germ cell tumour; Dys, dysgerminoma; IT, teratoma; YST, yolk sac tumour; MGCT, mixed germ cell tumour; PNET, primitive neuroectodermal tumour; HR, hazard ratio; CI, confidence interval (from Newton et al …”

“…Some of the authors of this review have recently published a retrospective series of ovarian germ cell tumours, concentrating on a number of different factors. 45 First, on review, even small areas of other elements meant assignation to a mixed germ cell tumour rather than a pure IT. Secondly, within the grading system of IT, cases where there was clear overgrowth and expansile obliteration of other elements was assigned to a category of 'somatic transformation'.…”

Recurrent ovarian immature teratoma in a 12-year-old girl: Implications for management

“…Confirmation of the wider applicability of this approach, i.e. avoiding adjuvant chemotherapy after surgery for IT, came from a recent report describing ovarian IT in adult patients [27]. Newton et al studied 138 patients across four large UK cancer centres over 12 years; EFS was 72% and OS 93% [27].…”

“…avoiding adjuvant chemotherapy after surgery for IT, came from a recent report describing ovarian IT in adult patients [27]. Newton et al studied 138 patients across four large UK cancer centres over 12 years; EFS was 72% and OS 93% [27]. They showed that adjuvant chemotherapy did not reduce future relapse or progression in IT patients and they observed no radiologic responses to chemotherapy in IT.…”