Introduction Our previous work showed that EOC patients who are homologous-recombination competent (HRC) have distinct per-operative characteristics including lower CA125 at presentation, infiltrative fibrotic tumour and lower optimal surgical cytoreduction rates (Mukhopadhyay et al, Cancer Res 2012). We hypothesized that HRC/BRCA-wild-type can be predicted based on tumour characteristics attributed to atypical tumour-stromal interaction leading to non-secretory phenotypes and higher desmoplasia resulting in poorer surgical outcomes.

Methods A prospective study of stage III/IV high grade serous EOC patients operated over 2 years (01/2021–12/2022) were analysed to score phenotypical HRC/BRCA(pHRC) status based on CA-125 levels, pattern of tumour spread and completeness of surgical cytoreduction (table 1). Pathological genomic HR status(gHRC) was determined from tumour tissue by Myriad MyChoice CDx Test assay. Reverse validation of pHRC score was performed against confirmed gHRC to assess predictability.

Results Of 40 patients enrolled, thirty were included for analysis. Reason for exclusion included insufficient tissue for HR profiling (n=4), inadequate assessment during surgery (n=4), unconfirmed primary site (n=2). Pattern of tumour spread was indeterminate in 12 patients and infiltrative in 13 patients. Pathologic HR analysis confirmed 19 patients were gHRC (genomic HRC). A pHRC score of ≥3 predicted gHRC with sensitivity of 73.6%, positive predictive value of 93.3% and specificity of 90.9%. All patients who scored 0 were proven to be HR deficient. Greatest discrepancy was noted in those with score of 2.

Conclusion/Implications Intraoperative tumour phenotype allows for accurate prediction of HRC status. Phenotypic HRC status can be useful surrogate for genomic HRD assay with wider implication where HRD testing is unavailable.