Abstract
Study question : What is the long-term impact on uterine volume of a childhood and adolescent, and young adult (AYA) exposure to chemotherapy?Summary answer : Compared to the control group, uterine volume was clinically significantly decreased after chemotherapy and even more after radio-chemotherapy.What is known already : Uterine damage is well-described after pelvic radiotherapy or total body irradiation (TBI) with decreased uterine volume and high obstetrical morbidity. Few studies have reported smaller uterus in AYA cancer survivors treated with chemotherapy only. In these studies, uterus volume was mostly assessed by a transabdominal and/or transvaginal ultrasonography, and primary diagnosis, age at treatment and chemotherapy regimen were heterogeneous. The uterine impact of chemotherapy is still little investigated.Study design, size, duration : A systematic review and meta-analysis on comparative studies. Searches were conducted on Medline, Embase and the Cochrane Library from 1990 to April 2023, using the main following search terms: cancer survivors, bone marrow transplantation, chemotherapy, radiotherapy, uterine volume. All studies reporting uterine volume in adult females who have received chemotherapy and/or radiotherapy during childhood and AYA < 25 years were included.Participants/materials, setting, methods : Two independent reviewers carried out the study selection, the bias assessment using the ROBINS-I tool and data extraction. The primary outcome was the uterine volume in mL. A Bayesian network meta-analysis (NMA) with meta-regression on parity and serious risk of bias was performed using a random-effects model. Furthermore sensitivity analyses were performed. Therapies were ranked by the surface under the cumulative ranking curve (SUCRA). Differences in means (MD) with 95% credible intervals (CrI) are reported.Main results and the role of chance : After review of 2 328 abstracts, 4 studies were selected for the meta-analysis. Uterine volume was assessed through ultrasonography in three articles and magnetic resonance imaging in one. Uterine volume data were available for 245 females after chemotherapy, 153 after radio-chemotherapy and 257 without cancer females (controls). SUCRA were 0.980 for control, 0.510 for chemotherapy and 0.009 for radio-chemotherapy. One study did not display data by parity (n = 165) and had a serious risk of bias, and was excluded in sensitivity analysis. SUCRA showed the same ranking order. In nulliparous females, compared to the control group (n = 152), uterine volume was decreased in the chemotherapy group (n = 138, MD = -12 mL; 95% CrI, -33, 5.7), and even more in the radio-chemotherapy group (n = 97, MD= -30 mL; 95% Crl -50, -13). In parous females, compared to the control group (n = 41), the decrease in the uterine volume tended to be similar in chemotherapy and radio-chemotherapy groups (MD = -27 mL; 95% CrI, -54, 3.2 with n = 43 and -30 mL; 95% CrI, -50, -13 with n = 19, respectively).Limitations, reasons for caution : The own responsibility of chemotherapy for inducing uterine damage is hard to be asserted because of the heterogeneity of radiology assay, and of the diversity of chemotherapy regimens, the lack of data concerning the Cyclophosphamide Equivalent dose, and about the hormonal status at the time of the uterine evaluation.Wider implications of the findings : Our results suggest a high probability that a childhood and AYA exposure to chemotherapy could induce uterine damage. Further studies are needed to evaluate the potential obstetrical impact of uterine damage caused by chemotherapy alone.