Ann H. Partridge

Fertility Preservation in People With Cancer: ASCO Guideline Update

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide updated fertility preservation (FP) recommendations for people with cancer. METHODS A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS One hundred sixty-six studies comprise the evidence base. RECOMMENDATIONS People with cancer should be evaluated for and counseled about reproductive risks at diagnosis and during survivorship. Patients interested in or uncertain about FP should be referred to reproductive specialists. FP approaches should be discussed before cancer-directed therapy. Sperm cryopreservation should be offered to males before cancer-directed treatment, with testicular sperm extraction if unable to provide semen samples. Testicular tissue cryopreservation in prepubertal males is experimental and should be offered only in a clinical trial. Males should be advised of potentially higher genetic damage risks in sperm collected soon after cancer-directed therapy initiation and completion. For females, established FP methods should be offered, including embryo, oocyte, and ovarian tissue cryopreservation (OTC), ovarian transposition, and conservative gynecologic surgery. In vitro maturation of oocytes may be offered as an emerging method. Post-treatment FP may be offered to people who did not undergo pretreatment FP or cryopreserve enough oocytes or embryos. Gonadotropin-releasing hormone agonist (GnRHa) should not be used in place of established FP methods but may be offered as an adjunct to females with breast cancer. For patients with oncologic emergencies requiring urgent oncologic therapy, GnRHa may be offered for menstrual suppression. Established FP methods in children who have begun puberty should be offered with patient assent and parent/guardian consent. The only established method for prepubertal females is OTC. Oncology teams should ensure prompt access to a multidisciplinary FP team. Clinicians should advocate for comprehensive FP services coverage and help patients access benefits. Additional information is available at www.asco.org/survivorship-guidelines .

Endometrial Cancer Risk Among Germline BRCA1/2 Pathogenic Variant Carriers: Review of Our Current Understanding and Next Steps

PURPOSE To review the literature exploring endometrial cancer (EC) risk among surgical candidates with germline BRCA1/2 pathogenic variants (PVs) to guide decisions around risk-reducing (rr) hysterectomy in this population. DESIGN A comprehensive review was conducted of the current literature that influences clinical practice and informs expert consensus. We present our understanding of EC risk among BRCA1/2 PV carriers, the risk-modifying factors specific to this patient population, and the available research technology that may guide clinical practice in the future. Limitations of the existing literature are outlined. RESULTS Patients with BRCA1/2 PVs, those with a personal history of tamoxifen use, those who desire long-term hormone replacement therapy, and/or have an elevated BMI are at higher risk of EC, primarily endometrioid EC and/or uterine papillary serous carcinoma, and may benefit from rr-hysterectomy. Although prescriptive clinical guidelines specific to BRCA1/2 PV carriers could inform decisions around rr-hysterectomy, limitations of the current literature prevent more definitive guidance at this time. A large population-based study of a contemporary cohort of BRCA1/2 PV carriers with lifetime follow-up compared with cancer-gene negative controls would advance this topic and facilitate care decisions. CONCLUSION This review validates a potential role for rr-hysterectomy to address EC risk among surgical candidates with BRCA1/2 PVs. Evidence-based clinical guidelines for rr-hysterectomy in BRCA1/2 PV carriers are essential to ensure equitable access to this preventive measure, supporting insurance coverage for patients with either BRCA1 or BRCA2 PVs to pursue rr-hysterectomy. Overall, this review highlights the complexity of EC risk in BRCA1/2 PV carriers and offers a comprehensive framework to shared decision making to inform rr-hysterectomy for BRCA1/2 PV carriers.