Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update

Diagnosis and treatment of ovarian cancer are challenging due to the lack of effective screening tools for advanced stages of disease. Advanced ovarian cancer, classified as the International Federation of Gynecology and Obstetrics stage III or IV, is traditionally treated with primary cytoreductive surgery (PCS) followed by chemotherapy. New evidence for neoadjuvant chemotherapy (NACT) has presented an alternative to this regimen, which could offer improvement for surgical outcomes and perioperative morbidity. This article is an update to current clinical guidelines with the newest evidence-based recommendations for interval cytoreduction versus primary cytoreduction and chemotherapy in patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (referred to under the umbrella of ovarian cancer). Guidelines were developed through a process of systematic review by an expert panel using a PubMed search fromMarch 2015 to April 2023. The review included phase III randomized controlled trials, meta-analyses, and cohort studies. Inclusion criteria for the studies were a population of patients with newly diagnosed stage III or IVovarian cancer, tests and procedures surrounding treatment, outcomes of treatment, and a study type of randomized controlled trial, multicenter cohort study,metaanalysis, or population-based observational data. Exclusion criteria were meeting abstracts that were not published in a peer reviewed journal, editorials, commentaries, letters, news articles, case reports, and narrative reviews, as well as articles published in a language other than English. Evidence suggests that extended surgical cytoreduction typically occurs at higher-volume hospitals and that these hospitals tend to have higher rates of complete gross resection. Low-volume hospitals were shown to have worse survival outcomes compared with medium- or high-volume locations; lower-volume facilities were also shown to have lower treatment regimen compliance. Evidence also suggests the predictive value for ovarian cancer surgery of different imaging modalities and genomic testing, showing that multimodal processes are most effective. Minimum testing should include a computed tomography scan of the abdomen and pelvis with contrast and, in some cases, additional assessment via laparoscopy or other imaging. For PCS, the updated literature review shows that PCS results in complete cytoreduction in approximately 40% to 50% of patients and that there is no significant difference in outcomes between PCS and NACT for initial treatment. Clinical recommendations based on this evidence conclude that PCS is the standard of care in individuals with maximally cytoreducible disease. In addition to this guidance, however, it is important for clinicians to consider surgical complexity and potential delays in starting NACT and the cost weighed against the benefit in each situation. The updated review on NACT provides evidence that it is associated with a reduction in postoperative deaths within 28 days, as well as reduced side effects such as severe nausea and vomiting. Additionally, those who had NACT followed by interval cytoreductive surgery (ICS) were at a lower risk of severe complications when compared with NACTand PCS. The recommendation for this area is that a gynecologic oncologist evaluate these patients for risk of complications and adjust accordingly on a case-by-case basis. This review also contains guidance on testing that should be performed before NACT, chemotherapy regimens, the combination of NACTand ICS, hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy after ICS, and maintenance therapy. There are several limitations acknowledged pertaining to the evidence provided; the heterogeneity of included studies means that generalizability can be somewhat limited, and heterogeneity in methods of treatment can introduce further bias into results and reduce the ability to compare studies. Future research should focus on stratifying patients based on molecular and genetic markers, tumor biology and histology, and personalizing treatment to optimize outcomes. The most important aspect of these guidelines is clear communication between clinician and patient and shared decision-making for the most benefit to everyone.

Duke Scholars

Author Stephanie Gaillard Medicine, Medical Oncology