The phased framework of oncology trials is designed to ensure patient safety and conserve resources by advancing only promising therapies from early- to late-phase testing. Despite decades of refinement, overall trial success rates-defined by the proportion of studies ultimately supporting regulatory approval-remain low, with failures increasingly occurring in late-phase studies. These failures are often contributed to by methodological shortcomings, including suboptimal end point selection, restrictive eligibility criteria, and inefficient trial designs. Although traditional approaches to biomarker discovery, outcome validation, and eligibility refinement have yielded transformational advances, increasing molecular subclassification of tumors into rare subgroups results in the conventional drug development framework being no longer fit for purpose. Artificial intelligence (AI) offers opportunities to enhance the efficiency, precision, and patient-centeredness of oncology trials. Deep learning systems integrate and analyze large data sets to uncover complex patterns often inaccessible to conventional methods. AI has potential applications in patient-trial matching, optimization of eligibility criteria, statistical modeling of survival outcomes, and the identification of novel surrogate end points although these applications remain largely investigational and are not yet established for routine use. This scoping review provides a structured overview of AI applications in oncology trials, with emphasis on outcome selection and surrogate end point evaluation. We also highlight emerging areas with potential for immediate implementation, such as patient selection, biomarker identification and synthetic control arms, to accelerate development and enhance clinical care. However, broader harmonization is needed to ensure reproducibility, transparency, and regulatory confidence before implementation. Ultimately, early and sustained collaboration between trialists, AI developers, and regulators will be essential to ensure that AI delivers meaningful advances in the design, evaluation, and delivery of new medicines.

Importance A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) treated with maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have exceptional response. Although licensing recommends continuing PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks of late progression, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) in patients with exceptional response are unknown. Objective To determine the long-term outcomes of patients with PS-ROC who have exceptional response to PARP inhibitors, and to explore genotype-phenotype associations. Design, Setting, and Participants This was an international, multicenter, retrospective cohort study of patients with exceptional response to PARP inhibitors, defined as patients with PS-ROC and progression-free survival (PFS) of 5 years or longer from PARP inhibitor commencement. The study was conducted across 41 sites in 14 countries from January 11, 2023, to November 10, 2025. Exposures Treatment with PARP inhibitors. Main Outcomes and Measures The primary end point was PFS, and secondary end points included overall survival, toxic effects, and dose reductions. Results A total of 320 patients with exceptional response (mean [SD] age, 56.4 [9.4] years) were included, with a median follow-up of 6.8 years (95% CI, 6.6-7.0 years). The median (IQR) PARP inhibitor duration was 75.0 (64.0-91.0) months. Of patients with exceptional response, 211 (65.9%) received continuous PARP inhibitors, but 109 (34.1%) discontinued: 34 (10.6%) due to physician recommendation, 2 (7.5%) had disease progression beyond 5 years, 22 (6.9%) had toxic effects, 17 (5.3%) for patient preference, and 12 (3.8%) for another reason. The 7.5-year and 10-year PFS rates were 88.8% (95% CI, 84.5%-93.3%) and 78.7% (95% CI, 70.5%-87.9%), respectively. Among the patients, 85 (26.6%) discontinued PARP inhibitors for reasons other than disease progression, with a 10-year PFS of 90.1% (95% CI, 80.6%-100%) vs 72.5% (95% CI, 60.3%-87.2%) for those who continued taking PARP inhibitors. Five patients (1.6%) were diagnosed with late-onset MDS/AML. Patients with exceptional response were enriched for variants in the BRCA1 RING domain and the BRCA2 DNA-binding domain. Conclusions and Relevance In this cohort study, most patients with exceptional response to PARP inhibitors remained progression free, including those who discontinued PARP inhibitors without progression. The risk of late-onset MDS/AML was low. These results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response and suggest that functional cure may be possible in patients with PS-ROC and exceptional response to PARP inhibitors.

Most cases of cervical cancer are still caused by persistent infection with high-risk human papillomavirus (HPV) variants, which also drives the development of ~30% of vulvar and ~76% of vaginal malignancies. Implementation of HPV vaccination has significantly decreased the incidence of high-grade pre-cancerous cervical, vulvar and vaginal lesions. However, cervical, vulvar and vaginal cancers can still develop (with or without HPV integration) and treatment options are limited compared to more common cancers. As with many other cancer types, molecular studies should identify targeted agents that could be added to treatment regimens to improve response rates and survival. Combination regimens involving chemoradiotherapy, anti-angiogenics and immune checkpoint inhibitors should be considered in the first instance. Then, depending on the molecular profile of a particular tumour, more targeted therapies should be considered. In particular, HER2-targeted therapies are likely to be a viable treatment option for many individuals, including those with cervical adenocarcinoma of gastric-type and vulvar Paget’s disease. In cervical cancer, TGFβ, PI3K, ATR and PARP inhibitors have shown some benefit and warrant further investigation. In vulvar cancer, combination therapies involving EGFR inhibitors require ongoing evaluation. In vaginal cancer, combination therapies targeting the PI3K and MAPK pathways should be investigated for squamous cell carcinoma and melanoma, respectively. Finally, with the rapid expansion of antibody-drug conjugates in recent years, this is an especially exciting area of investigation. For cervical, vulvar and vaginal cancers specifically, trastuzumab deruxtecan and tisotumab vedotin could be important therapeutic options in the right context. In this review, we describe the molecular features of different cervical, vulvar and vaginal cancer types, current genomically-matched therapies being investigated and discuss treatment strategies with future potential.

Background:Novel therapeutics are urgently needed for high-grade serous ovarian cancer (HGSOC). We identified the receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a therapeutic target. NBE-002, an antibody-drug conjugate (ADC) consisting of a humanised anti-ROR1 antibody, huXBR1-402, linked to a highly potent anthracycline-derivative (PNU), has activity in ROR1-positive haematologic malignancies. Objectives:This study explored the anti-cancer effects of NBE-002 alone and in combination with standard HGSOC therapies, carboplatin, paclitaxel and olaparib. Design:A ROR1-ADC was tested in cell lines and in vivo models of HGSOC. Methods:Different ROR1-targeting antibodies and payload compositions were constructed and tested in vitro. The dose effect of NBE-002 alone and in combination with carboplatin, paclitaxel or olaparib was analysed in ROR1+ HGSOC cell lines. Growth inhibition and apoptosis were monitored by live cell imaging and combination effects determined. Ten HGSOC PDX models were treated with NBE-002 alone, or in combination with carboplatin or olaparib, over 4 weeks and tumour volume and overall survival evaluated. Results:Synergistic interaction was observed in two out of five HGSOC cell lines treated with NBE-002 and carboplatin (PEO4 and OC023, chemo-resistant), in one out of five treated with NBE-002 and olaparib (PEO1, BRCA2 mutated, HR deficient) and none of five treated with NBE-002 and paclitaxel. In vivo, NBE-002 exhibited activity in PA-1 xenografts and three HGSOC PDX models with high ROR1 expression, platinum sensitivity and homologous recombination DNA repair deficient (HRD). When NBE-002 was combined with carboplatin, activity was observed in 7 of 10 ROR1-expressing PDX models, regardless of platinum or HRD status. The activity was demonstrated in combination with olaparib in both PDX tested, one HRD and one HRD reverted. Conclusion:The ROR1-targeting ADC, NBE-002, has therapeutic potential in HGSOC, with single agent activity observed both in vitro and in vivo. Broader clinical applications were evident when NBE-002 was combined with carboplatin or olaparib.

INTRODUCTION:Women aged ≥70 years with ovarian cancer (OC) may experience variations in care compared to best practice guidelines, and their five-year survival is significantly lower compared to women aged <70 years. The National Gynae-Oncology Registry (NGOR) is Australia's first clinical quality registry (CQR) for gynaecological cancers, measuring patterns of care using 15 OC clinical quality indicators (CQIs) reflecting evidence-based practice. This study aimed to compare adherence to CQIs for older versus younger groups with newly diagnosed OC and evaluate differences in 5-year overall survival (OS). MATERIALS AND METHODS:This is a multi-centre, observational study utilizing NGOR data for women with newly diagnosed OC at participating sites (May 2017 to July 2022). Demographics, CQIs, and clinical variables were compared between women aged ≥70 years (older group) and those aged <70 years (younger group). Five-year OS was estimated. RESULTS:A total of 1628 women were eligible. Median OS was 3.37 years (95 % CI: 3.05-3.86 years) in the ≥70 group versus not reached in the younger group aged <70 (95 % CQI: 5.95 - n/a years). Compared to the younger group, older women less frequently received first-line platinum-taxane doublet chemotherapy (69.1 % vs 91.6 %, p < 0.001) and first-line chemotherapy with a platinum-taxane doublet plus bevacizumab (18.9 % vs 29.9 %, p = 0.02). Older women were less likely to achieve primary surgery with no macroscopic residue (46.4 % vs 60.8 %, p = 0.03) and had lower clinical trial enrolment (15.5 % vs 21.7 %, p = 0.005). After adjusting for ECOG Performance Status, histological sub-type, cancer stage, and treatment group, five-year OS remained significantly lower in the older women with an adjusted HR for death 1.50 (95 % CI: 1.27-1.76, p = 0.001). DISCUSSION:Significant differences in care were observed in older women with OC, notably in achieving complete primary surgical cytoreduction, utilization of standard chemotherapy regimens, and trial enrolment. Survival for older women remains significantly lower than for younger women after adjustment. These findings highlight specific areas for potential quality improvement in the care of older Australian women with OC.

DNA methyltransferase 1 inhibitor (DNMT1i) therapy is a promising option for increasing immune response as part of combination cancer therapy. High-grade serous ovarian carcinoma (HGSOC) is a highly aggressive cancer with poor survival outcomes, where DNMT1i therapy is being increasingly explored. HGSOC with epigenetically silenced BRCA1 has been shown to respond to PARP inhibitor (PARPi) treatment – a core targeted therapy for HGSOC. However, loss of silencing of even a single BRCA1 allele causes PARPi and platinum chemotherapy resistance. We tested whether BRCA1 silencing was robust to DNMT1i therapy, or would be reversed, thus driving PARPi resistance. We previously generated two homozygously silenced BRCA1 HGSOC cell lines: WEHI-CS62 and an OVCAR8 derivative. DNMT1i treatment caused sustained BRCA1 promoter methylation loss, gene re-expression and PARPi resistance in both of these silenced BRCA1 lines, but not in mutated BRCA1/2 or RAD51C lines. Methylation arrays confirmed transient global CpG methylation losses following DNMT1i. CRISPR deletion of the re-expressed BRCA1 copy in WEHI-CS62 restored silencing and PARPi sensitivity. Furthermore, DNMT1i treatment of a silenced BRCA1 PDX caused heterogeneous BRCA1 promoter methylation loss. In summary, DNMT1 inhibitors caused sustained reduction of BRCA1 promoter methylation in HGSOC cells. This resulted in BRCA1 re-expression and PARP inhibitor resistance, presenting a significant risk for up to 17% of HGSOC patients with BRCA1 gene silencing who could benefit from PARP inhibitor therapy. We conclude that DNA demethylation therapy should be avoided for HGSOC patients with epigenetically silenced BRCA1 . ### Competing Interest Statement CLS and CV declare venetoclax royalties paid to the institution with a portion distributed to contributors. OK has received consulting fees from XING Genomic Services and has received travel honorarium from AstraZeneca. Remaining authors declare no potential conflicts of interest.

Supplementary Figures S1-S13

Background: The identification of pathogenic variants in the Breast Cancer Genes 1 and 2 (BRCA1/2) is a critical predictive biomarker for poly (ADP-ribose) polymerase inhibitor (PARPi) therapy in epithelial ovarian cancer (EOC). The aim of this study is to define real-world rates and determinants of germline and somatic BRCA1/2 testing and subsequent PARPi utilisation in Australia using a national clinical quality registry. Methods: This multi-centre cohort study analysed data from 1503 women with non-mucinous EOC diagnosed between May 2017 and July 2022, captured by the Australian National Gynae-Oncology Registry (NGOR). We evaluated rates of germline and somatic testing and PARPi use, using multivariate logistic regression to identify associated clinical and demographic factors. Results: Overall germline and somatic testing rates were 68% and 32%, respectively. For the high-grade serous ovarian cancer (HGSOC) cohort, rates were higher, at 78% and 39%, respectively. Germline testing was significantly less likely for women aged >80 years (OR 0.49), those in regional areas (OR 0.61), and those receiving single-modality treatment. Somatic testing uptake increased significantly following public reimbursement for PARPi (p = 0.004). Among eligible women with a newly diagnosed BRCA pathogenic variant and advanced disease (n = 110), 52% commenced first-line maintenance PARPi. Conclusions: This national study offers valuable insights into Australian ovarian cancer care, highlighting opportunities to enhance testing equity for older women (aged >80) and regional patients. Furthermore, it identifies the translation of a positive test into PARPi therapy as a complex area that warrants further collaborative investigation to optimise patient outcomes.

Supplementary Tables S1-S11

Up to 17% of high grade serous ovarian carcinomas (HGSOC) harbour BRCA1 promoter methylation (meBRCA1), making them susceptible to treatment with targeted PARP inhibitor (PARPi) therapy. Unfortunately, meBRCA1 loss can be acquired following PARPi or platinum chemotherapy, resulting in BRCA1 re–expression and PARPi resistance. Our understanding of meBRCA1 stability in HGSOC is currently limited, in part due to a paucity of pre–clinical models with homozygous meBRCA1. Herein, we describe the generation of a several OVCAR8 cell line derivatives containing landing pad constructs, for future functional studies, and representing various BRCA1 states, including a homozygous meBRCA1 variant. Our PARPi resistant OVCAR8 has two methylated BRCA1 copies and one unmethylated copy, enabling BRCA1 expression. CRISPR–Cas9 gene editing was used to delete copies of the BRCA1 gene in landing pad–containing clones of this cell line (A6 and H4). We produced one variant with deletion of all BRCA1 copies (H4–53), and another with two copies deleted and only a single methylated gene copy remaining (A6–30 – validated further using nanopore long–read sequencing). These both lacked BRCA1 gene expression and were sensitive to PARPi treatment. The A6–30 line was transplanted into immunocompromised mice to generate a xenograft model that retained homozygous meBRCA1 and demonstrated some response to PARPi in vivo. Thus, using CRISPR gene editing we have created several novel isogenic HGSOC cell line models, including one with homozygous meBRCA1, that will support future studies of meBRCA1 stability and PARPi resistance. ### Competing Interest Statement The authors have declared no competing interest.

5565 Background: Platinum resistant high grade serous ovarian cancer (HGSC) is associated with a poor prognosis and limited treatment options. Immune checkpoint inhibitors have failed to show significant impact in treatment of HGSC to date. Bevacizumab (anti-VEGF) and atezolizumab (anti-PDL1) have shown synergy in multiple cancer types. Cobimetinib (MEK inhibitor) may also potentiate immune responses, particularly by altering the tumour microenvironment. We sought to evaluate the efficacy of cobimetinib, bevacizumab and atezolizumab in women with platinum resistant HGSC. Methods: BEACON is a Phase II single arm study of cobimetinib (60mg oral D1-21 q 28-days), bevacizumab (5mg/kg IV q2w) and atezolizumab (840mg IV q2w from Cycle 2) in patients with platinum-resistant recurrent HGSC. Patients continued therapy until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) according to RECIST 1.1 at 24 weeks. Secondary endpoints included best overall response (BOR), safety, progression free survival, and response duration. Correlative studies on paired tumor biopsy and blood samples will explore molecular characteristics/subtypes and potential biomarkers of response as exploratory objectives. This study has now completed accrual and we present the 24-week response data, with a data cut off 21st December 2023. Results: Twenty-nine patients were enrolled between September 2018 and June 2023. Median age was 62 years (range 37 - 79) and 97% had received ≥ 2 prior lines of chemotherapy. The median number of cycles received was 3 cycles of atezolizumab and cobimetinib, and 4 cycles of bevacizumab. The ORR at 24 weeks was 21% [95% CI: 8-40], and a further 28% had stable disease as assessed per RECIST. Five patients (17%) have remained on study treatment for ≥ 52 weeks to date, suggesting that in some patients there was durable disease control. In terms of safety, 22 patients (76%) required a dose reduction in cobimetinib, mainly due to gastrointestinal and skin toxicity. Seventeen patients (59%) experienced a ≥Grade 3 treatment related adverse event, most commonly hypertension (6 patients, 21%). Two patients (7%) discontinued all study treatments due to toxicity. Conclusions: Preliminary results from this study show promising efficacy with the combination of atezolizumab, bevacizumab and cobimetinib in platinum resistant HGSC. Duration of response, progression free survival data and translational data exploring molecular characteristics will be presented as data matures. Clinical trial information: NCT03363867 . [Table: see text]

BACKGROUND:Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma. METHODS:We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma. Data on chemotherapy outcomes including objective response rate, progression-free survival (PFS), and overall survival were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by mismatch repair status. We also compared differences in PFS and overall survival outcomes by creating individual patient data from the Kaplan-Meier curves of trial publications for sensitivity analyses. RESULTS:A total of 5 RCTs with 1137 participants (mismatch repair deficient, 26%; mismatch repair proficient, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the mismatch repair deficient and mismatch repair proficient subgroups for objective response rate (66.5% vs 64.0%; P = .20 for subgroup difference), PFS (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.77 to 1.12; P = .44; median PFS = 7.6 vs 9.5 months) or overall survival (HR = 1.03, 95% CI = 0.73 to 1.44; P = .88; median overall survival = not reached vs 28.6 months). CONCLUSIONS:Objective response rate, PFS, and overall survival were similar among those with mismatch repair deficient vs mismatch repair proficient endometrial cancer treated with front-line, platinum-doublet chemotherapy in RCTs. These findings reinforce the importance of combining chemotherapy together with immune checkpoint inhibitors until the results of trials comparing immune checkpoint therapy alone with combination therapy are available.

OBJECTIVE:The Rare Ovarian Tumor Module forms part of the National Gynae-Oncology Registry (NGOR) which measures compliance with the optimal care pathways for gynecologic cancer in Australia. Our objectives were to evaluate patterns of care in patients with non-epithelial ovarian tumors and to develop appropriate clinical quality indicators. METHODS:A multidisciplinary reference group developed a module dataset in the NGOR REDCap database to collect clinical data using an opt-out recruitment model across participating Australian hospitals. Clinical quality indicators were developed and refined using consensus methods, with annual reports provided to participating sites to benchmark performance and drive improvement in patient care. RESULTS:As of November 2023, 232 patients from 18 Australian hospitals were enrolled. All cases had histologic confirmation with the majority being adult granulosa cell tumors (47.8%). Almost all patients (97.8%) were presented at a multidisciplinary team meeting. Most had early-stage disease (stage, I 70.3%; II 9.9%; III 9.1%; IV 3.4%; not documented 7.3%) and had surgery alone (72.4%). Thirty-four patients underwent multiple surgeries as primary treatment (14.7%), with a median time to a second surgical procedure of 47 days (interquartile range 36-71). Two-thirds of patients (65.4%) had their first surgery performed by a gynecologic oncologist. Rates of intra-operative and 30-day post-operative adverse events (Clavien-Dindo ≥ grade III) were low, 4.3% and 1.9% respectively. Of 52 patients with stage II disease and higher, 37 (71.2%) received systemic therapy. A high rate of adherence to the 4 clinical quality indicators as measures of best practice care was observed. CONCLUSIONS:The NGOR Rare Ovarian Tumor Module has successfully collated relevant data to study patterns of care to inform the development of clinical quality indicators and enable research for these rare tumors. This national collaboration has the potential for benchmarking outcomes in Australia with international experience.

Despite significant advances in treatments, ovarian cancer (OC) remains one of the most prevalent and lethal gynecological cancers in women. The frequent detection at the advanced stages has contributed to low survival rates, resistance to various treatments, and disease recurrence. Thus, a more effective approach is warranted to combat OC. The cytokine Interleukin-6 (IL6) has been implicated in various stages of OC development. High IL6 levels are also correlated with a lower survival rate in OC patients. In this current review, we summarized the pivotal roles of IL6 in OC, including the initiation, development, invasion, metastasis, and drug resistance mechanisms. This article systematically highlights how targeting IL6 improves OC outcomes by altering various cancer processes and reports the ongoing clinical trials that would further shape the IL6-based targeted therapies. This review also suggests how combining IL6-targeted therapies with other therapeutic strategies could further enhance their efficacy to combat OC.

PURPOSE Despite increasing evidence of benefit supporting complex genomic sequencing (CGS) in personalizing cancer therapy, its widespread uptake remains limited. METHODS This mixed-methods, prospective cross-institutional demonstration study was designed to evaluate implementation of CGS in the care of patients with advanced cancer. DNA sequencing was undertaken on formalin-fixed paraffin-embedded tumor and matched blood was completed with the Peter MacCallum Cancer Centre Comprehensive Cancer Panel; 391 genes via central laboratory. Oncologists performed consent and result delivery. Patients completed pre- and post-test surveys, including validated and study-specific questions and, if eligible, semistructured interviews. Qualitative interviews were undertaken with study clinicians to evaluate processes. RESULTS One hundred ninety-nine (63%) had ≥1 finding with the potential to affect management, including 172 (55%) whose finding could affect their treatment options, 25 (8%) whose test led to the resolution of diagnostic ambiguity, and 49 (16%) with a pathogenic germline variant. In 6-month follow-up, 50 (16%) participants had their subsequent therapy changed on the basis of their CGS results. Two hundred ninety-three (88% of adult patients) completed surveys at three time points. At consent, patients cited multifaceted value in testing, showed good understanding of basic concepts, but most (69%) overestimated the likelihood of result-led change. Post-test patients remained consistently satisfied with accessing CGS. 21% struggled with understanding results but there were low levels of decisional regret after participation (89% had nil/mild regret). Clinicians cited collaboration and communication as critical to delivery. CONCLUSION Patients undergoing CGS are generally satisfied and place value on its use beyond potential therapeutic benefit. Our results suggest that to improve test utility and delivery of CGS with value to patients and investing institutions, focus must be placed on addressing the additional barriers to its wider implications including efforts to improve process efficiencies, clinician genomic literacy, and decision-making support.

PURPOSE Cancer antigen-125 (CA-125) is recommended by treatment guidelines and widely used to diagnose ovarian cancer recurrence. The value of CA-125 as a surrogate for disease progression (PD) and its concordance with radiologic progression are unclear, particularly for women with platinum-sensitive relapsed ovarian cancer (PSROC) who have responded to chemotherapy and treated with maintenance poly(ADP-ribose) polymerase inhibitor (PARPi). METHODS In this pooled analysis of four randomized trials of maintenance PARPi or placebo (Study 19, SOLO2, ARIEL3, and NOVA), we extracted data on CA-125 PD as defined by Gynecologic Cancer InterGroup criteria and RECIST v1.1. We evaluated the concordance between CA-125 and RECIST PD and reported on the negative predictive value (NPV) and positive predictive value (PPV). RESULTS Of 1,262 participants (n = 818 PARPi, n = 444 placebo), 403 (32%) had CA-125 PD, and of these, 366 had concordant RECIST PD (PPV, 91% [95% CI, 88 to 93]). However, of 859 (68%) without CA-125 PD, 382 also did not have RECIST PD (NPV, 44% [95% CI, 41 to 48]). Within the treatment arms, PPV remained high (PARPi, 91% [95% CI, 86 to 94]; placebo, 91% [95% CI, 86 to 95]) but NPV was lower on placebo (PARPi, 53% [95% CI, 49 to 57]; placebo, 25% [95% CI, 20 to 31]). Of 477 with RECIST-only PD, most (95%) had a normal CA-125 at the start of maintenance therapy and the majority (n = 304, 64%) had CA-125 that remained within normal range. Solid organ recurrence without peritoneal disease was more common in those with RECIST-only PD than in those with CA-125 and RECIST PD (36% v 24%; P < .001). CONCLUSION In patients with PSROC treated with maintenance PARPi, almost half with RECIST PD did not have CA-125 PD, challenging current guidelines. Periodic computed tomography imaging should be considered as part of surveillance, particularly in those with a normal CA-125 at the start of maintenance therapy and on treatment.