BACKGROUND AND HYPOTHESIS:Malignancy, driven by the effects of immunosuppression, is a major complication following kidney transplantation. The widespread and non-pathogenic TT virus (TTV) has emerged as a surrogate of the immune status of its host, with prior studies linking TTV load to insufficient and excessive immunosuppression and thus indirectly to graft rejection and infection. Its relationship to malignancy in kidney transplant recipients is unknown. METHODS:This prospective observational single center study evaluated 428 patients who underwent kidney transplantation between 2016 and 2019. TTV was quantified by qPCR in plasma and the primary outcome was the incidence of the first malignancy during years 2-5 post-transplant. RESULTS:In total 53 patients developed a malignancy (53% cutaneous keratinocyte cancer). The mean log10 TTV load during months 4 to 12 post-transplant (logTTVm4-12) was associated with increased malignancy risk with a hazard ratio (HR) of 1.25 (95% CI 1.02-1.54) in unadjusted analysis and 1.20 (95% CI 0.97-1.48) after adjustment for age, sex, smoking, and body mass index. In a subgroup, the result remained consistent after additional adjustment for tacrolimus and mycophenolate exposure (HR 1.31, 95% CI 1.03-1.67). Patients with logTTVm4-12 > 8, a cut-off we previously proposed to indicate infection risk, had a HR of 2.10 (95% CI 1.22-3.60). CONCLUSIONS:These findings suggest that a high TTV load-indicating a state of intense immunosuppression-predicts malignancy after kidney transplantation. Monitoring TTV as a marker of immunosuppression may offer a novel strategy for personalizing immunosuppressive therapy and reducing cancer risk.

Objective To assess risk factors for long-term recurrence of vulvar high-grade squamous intra-epithelial lesions (vulvar HSIL) and other high-risk human papillomavirus-related genital dysplasia after primary treatment with imiquimod or surgery. Methods This was a long-term follow-up of the PITVIN trial (Clinicaltrials.gov identifier: NCT01861535), a multi-center, randomized, phase 3 non-inferiority clinical study of topical imiquimod versus surgery for vulvar HSIL. Number of recurrent vulvar HSIL or other HSIL and related treatment types were assessed. The relationship between initial study treatment, patient characteristics, primary response (quick versus slow) to imiquimod, and pre-treatment immune infiltrates in recurrent and non-recurrent HSIL were analyzed. Results Long-term clinical data was available for 87 patients (42 imiquimod, 45 surgery) of the 107 patients included in the original intention-to-treat analysis. Mean follow-up time was 70 months (standard deviation ±24). Among the 80 patients with per-protocol treatment in the initial study, recurrent vulvar HSIL was diagnosed in 33% (12/36) after imiquimod and in 20% (9/44) after surgery (p =.20). Baseline recurrence status, age, and smoking were not associated with vulvar HSIL recurrence. Within the imiquimod study group, patients with an initial slow or partial response to imiquimod experienced recurrent HSIL lesions in 54% (7/13), and patients with an initial quick response in 22% (5/23) of cases (p =.05). Recurrent vulvar HSILs showed significantly higher initial intra-epithelial infiltration of cluster of differentiation 33+ immature monocytes compared with non-recurrent lesions (p =.04), suggesting tumor-mediated immunosuppression. In the intention-to-treat population, 21% (18/87) developed cervical HSIL (n = 9), vaginal HSIL (n = 3), anal HSIL (n = 3), cervical cancer (n = 1), anal cancer (n = 1) and vulvar cancer (n = 1) during long-term follow-up. Conclusions Topical imiquimod and surgical treatment of vulvar HSIL are effective in long-term follow-up, with recurrences occurring in 20% to 33% of patients within 5 years. Initial slow or partial treatment response to imiquimod and the composition of pre-treatment immune infiltrates may be predictors of an increased long-term recurrence risk.

OBJECTIVE:To compare oncologic outcomes and perioperative morbidity between simple hysterectomy (SH) and radical hysterectomy (RH) in patients with and without very low-risk early-stage cervical cancer from the phase III Simple Hysterectomy And PElvic node assessment (SHAPE) trial. METHODS:Patients who underwent SH or RH in the SHAPE trial were classified into the Conservative SHAPE group (very low-risk), meeting criteria similar to the ConCerv trial, and the Liberal SHAPE group (without very low-risk), including everyone else. Between the SH and RH arms in each group, survival outcomes, including recurrence-free survival (RFS) and overall survival (OS), and intraoperative and postoperative morbidities were compared. Factors associated with recurrence and mortality rates were also investigated. RESULTS:In the Conservative SHAPE group (n = 107), no recurrence was observed in either SH or RH arms, and only one non-cancer-related death in the RH arm during a median follow-up of 4.5 years. In the Liberal SHAPE group (n = 575), the SH arm showed similar 3-year pelvic RFS (96.9 % vs. 97.4 %; HR, 1.15; 95 % CI, 0.49-2.70), extrapelvic RFS (97.7 % vs. 99.6 %; HR, 3.64; 95 % CI, 0.76-17.5), overall RFS (95.4 % vs. 97.4 %; HR, 1.56; 95 % CI, 0.70-3.48), and OS (98.9 % vs. 99.3 %; HR, 1.21; 95 % CI, 0.41-3.59), compared with the RH arm. In multivariate analyses, SH was not associated with recurrence and mortality rates, while absence of residual disease in the hysterectomy specimen was associated with lower recurrence. In both groups, SH was associated with a lower risk of urinary retention and incontinence. CONCLUSION:There were similar recurrence and survival outcomes but less morbidity from SH compared to RH in patients with and without very low-risk early-stage cervical cancer from the SHAPE trial.

TPS5645 Background: Despite advancements in frontline therapies for EC, treatment options for recurrent/refractory disease remain limited. HER2 overexpression in EC is associated with rapid disease progression, tumor invasiveness, a high risk of recurrence, and poor prognosis. Trastuzumab pamirtecan (T-Pam; BNT323/DB-1303) is an investigational HER2-targeting antibody-drug conjugate (ADC) with a DNA topoisomerase I inhibitor payload and a drug-to-antibody ratio of ~8. In a phase 1/2a trial (NCT05150691), T-Pam demonstrated encouraging clinical benefit in patients with HER2-expressing EC, efficacy was observed across all HER2 expression levels and patient subgroups with a manageable safety profile. Methods: Following a protocol amendment, this open-label, randomized, multi-site, phase 3 trial (Fern-EC-01; BNT323-01) is enrolling patients with recurrent, HER2 expressing EC (assessed by central laboratory testing using IHC) who have measurable disease defined by RECIST v1.1, an ECOG PS of 0-2, and have received ≥1 prior line of platinum-based therapy (in any setting) and prior immune-checkpoint inhibitor treatment. Up to three lines of prior therapy are permitted. Prior hormonal therapy and radiation are allowed but do not count as prior lines of therapy. Prior exatecan-containing treatment is not allowed. All patients will receive treatment until RECIST v1.1 defined progressive disease, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. The trial is enrolling two cohorts. In Cohort 1, ≈420 patients with HER2-expressing (IHC 1+ or 2+) EC will be randomized 2:1 to evaluate the efficacy and safety of T-Pam vs investigator’s choice of chemotherapy (doxorubicin, paclitaxel, or docetaxel in case of contraindication to paclitaxel and availability at the site). Stratification is based on HER2 expression (IHC 1+; 2+) and prior lines of therapy (1; 2+). The primary endpoint for Cohort 1 is progression-free survival (PFS) by blinded independent central review (BICR); overall survival is a key secondary endpoint. In Cohort 2, ≈60 patients with HER2 IHC 3+ EC will receive T-Pam; the primary endpoint for this cohort is objective response rate by BICR. Enrollment is ongoing globally. Clinical trial information: NCT06340568 .

OBJECTIVE:To evaluate the concordance between preoperative loop electrosurgical excision procedure (LEEP)/cone margins, pelvic magnetic resonance imaging, and final pathology from the hysterectomy specimen in the CX.5/SHAPE trial. METHODS:This exploratory analysis included patients who underwent preoperative LEEP/cone biopsy and pelvic magnetic resonance imaging prior to hysterectomy. Primary outcomes included the correlation between pelvic magnetic resonance imaging and final pathology: (1) "undercall" (no disease on magnetic resonance imaging but disease on final pathology); (2) "overcall" (disease on magnetic resonance imaging but none on final pathology), and (3) "concordance" (disease or no disease on both magnetic resonance imaging and final pathology), Oncologic outcomes were evaluated according to the 3 magnetic resonance imaging groups. Magnetic resonance imaging sequences included T1 and high-resolution T2, and diffusion-weighted imaging; the use of gadolinium was not mandatory. RESULTS:A total of 480 patients had a pelvic magnetic resonance imaging performed after a diagnostic LEEP/cone procedure. The magnetic resonance imaging undercall rate was 27.1% (95% confidence interval 23.2% to 31.3%), the overcall rate 8.5% (95% confidence interval 6.2% to 11.4%), and concordance rate 64.4% (95% confidence interval 59.5% to 68.7%) with sensitivity of 30.5% (95% confidence interval 24.0 to 37.6) and specificity of 86.0% (95% confidence interval 81.5 to 90.0) for residual disease. Higher magnetic resonance imaging concordance was associated with negative versus positive LEEP/cone margins (76.6% vs 57.3%, p < .0001). Adenocarcinoma was associated with a lower positive predictive value (41.9%) compared to squamous (66.2%) and adenosquamous (50%) (p = .04). Overall, 10 patients had no disease on preoperative magnetic resonance imaging and tumors greater >2 cm on final pathology (undercall); 6 had simple hysterectomy (under-treatment). Conversely, 41 patients had disease on preoperative magnetic resonance imaging and no residual disease on final pathology (overcall); 20 had radical hysterectomy (over-treatment). There were no differences in pelvic recurrences (p = .09) or deaths (p = .16) between magnetic resonance imaging correlation groups. Positive LEEP/cone margins and residual disease on magnetic resonance imaging were associated with more adjuvant treatment (13.0%) compared with negative margins and no disease on magnetic resonance imaging (2.5%). CONCLUSIONS:There was modest concordance between preoperative magnetic resonance imaging following LEEP/Cone procedure and final hysterectomy pathology in the SHAPE trial, but there was limited impact on rates of under- and over-treatment.

Lynch syndrome (LS) is a hereditary condition associated with an increased susceptibility to developing cancer, primarily colorectal and gynaecological cancer (endometrial cancer and ovarian cancer). The European Society of Gynaecological Oncology (ESGO) nominated fifteen practicing multidisciplinary clinicians with expertise in this field and ten gynaecological and oncological fellows with interest in the topics to develop evidence-based statements, sharing and standardizing the management of LS carriers. Published evidence was integrated with clinical experience to reach Consensus Statements through anonymous voting. In this Consensus, thirty-one statements based on the best available evidence and expert agreement are offered. They focused on genetic and cancer risk counseling principles, screening procedures, risk-reducing surgical and medical strategies, and address emerging topics such as reproductive issues for LS carriers, which are important in current practice. This manuscript reports the Statements that reached a consensus, their voting results, and a summary of supporting evidence.

Abstract Background: Complete macroscopic tumor resection estimation as visualized by the surgeon is the foremost prognostic factor in high-grade serous ovarian cancer (HGSOC). Objective measures of postoperative molecular residual disease (MRD) are lacking, including serologic and radiologic evaluation. Tumor-informed circulating tumor DNA (ctDNA) has shown promise as a new approach to identify patients at higher risk for relapse. Methods: This prospective bicentric study included advanced HGSOC patients (pts) undergoing primary debulking surgery (PDS), six cycles of chemotherapy and maintenance therapy (07/2021 - 09/2024). Whole-genome sequencing of tumor tissue identified structural variants, used to design personalized multiplex dPCR assays to detect MRD. Plasma samples were collected: perioperatively (preop, postop day[d]2 and d10), during chemotherapy (C1, C3, C6) and every 3 months (mo) until progression or 24 mo of follow up (FU). CA-125 was analyzed accordingly (cutoff 35 kU/L). Statistics included chi-square and log-rank tests, multivariate Cox model and Kaplan-Meier estimates for progression-free survival (PFS). Results: 33/84 pts (39%) experienced relapse with a median PFS of 12.0 mo during a median FU time of 15.4 mo. ctDNA was detected in 77/82 pts (94%) at baseline and in 63/74 pts (85%) postoperatively. At postop d10, pts with complete tumor resection had significantly lower ctDNA levels than pts with postop residual disease (p=0.0018). Median ctDNA level decreased by 94% between preop and postop d10 in pts with complete tumor resection (p=0.0247), but not in pts with postop tumor residuals (p=0.891). Within the pt subgroup with complete tumor resection, ctDNA clearance at C1 (20%) and C6 (70%) was associated with significantly lower recurrence risk compared to persistent ctDNA levels (C1: 80%, C6: 30%) with a stronger association at C6 (C1: HR=3.39, p=0.0470, C6: HR= 52.21, p<0.0001). Median time to recurrence in the C6 ctDNA positive group was 10.7 mo compared to 21.3 mo in the ctDNA negative group. This effect was not observed at postop d10 (p=0.273) or for pts with residual tumor. ctDNA outperformed CA-125 for prognosis, as CA-125 levels at C1 or C6 failed to predict recurrence (C1: p=0.189; C6: p=0.165). In a multivariate analysis, ctDNA persistence at C6 (HR=14.58, p<0.0001) and postoperative residual tumor were confirmed as independent prognostic markers. Conclusion: Tumor-informed ctDNA analysis can further accurately stratify HGSOC pts at high risk of recurrence despite primary surgery with complete macroscopic resection. ctDNA assessment at C6 may provide an opportunity window for risk-stratified treatment adjustments directly after chemotherapy, enabling new personalized maintenance strategies. Citation Format: Magdalena Postl, Christina Victoria Tauber, Valentina Glueck, Mira Maria Gliga, Nuria Segui, Karen Howarth, Miguel Alcaide, Lucia Oton, Gerda Hofstetter, Isabelle Maurer, Alexander Burges, Sven Mahner, Mirjana Kessler, Melina Danisch, Stephan Polterauer, Nicole Concin, Christoph Grimm, Fabian Trillsch. Tumor-informed circulating tumor DNA identifies high-grade serous ovarian cancer patients at highest risk for recurrence despite optimal first-line treatment with primary macroscopic complete resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1061.

The current study aimed to assess oncologic safety with 24-month groin recurrence rates after the exclusive use of indocyanine green (ICG) for sentinel node (SLN) detection in early-stage, node-negative vulvar cancer. This retrospective cohort study descriptively assessed consecutive patients with early (T1/2 < 4 cm) squamous vulvar cancer who underwent exclusive ICG-based inguinal sentinel node-mapping without radioactive tracer or blue dye. Data of 49 patients encompassing 94 groins at risk were available for analysis. The SLN detection rate was 90.4

BackgroundHigh-grade serous ovarian cancer is one of the most lethal malignancies in women, typically diagnosed at an advanced stage, treated with debulking surgery, platinum-based chemotherapy and maintenance therapy, and associated with a high risk of recurrence even after optimal treatment. Myelodysplastic syndrome is a rare but serious haematological disease which can occur after exposure to chemotherapy or PARP inhibitor therapy. Treatment of recurrent disease in patients who develop Myelodysplastic syndrome is particularly challenging due to the significant myelotoxicity associated with standard cytotoxic chemotherapy. Mirvetuximab soravtansine is an antibody-drug conjugate approved for use in platinum-resistant folate receptor alpha-positive high-grade ovarian cancer. Due to its limited myelotoxicity, it might be an interesting treatment option in patients with relevant haematologic side effects due to previous lines of chemotherapy.CaseWe report on a patient with a recurrence of platinum-sensitive ovarian cancer (platinum-free interval: 16 months) who developed Myelodysplastic syndrome and ultimately, probably an acute Myeloid Leukaemia. Chemotherapy re-challenge with platinum-based combination chemotherapy was not feasible due to persistent thrombocytopenia (CTCAE grade 3). Therefore, treatment with mirvetuximab soravtansine was initiated showing durable response with a progression-free survival of nine months. The patient’s platelet count and tumor marker CA125 remained stable for nine months while she was receiving antibody-drug conjugate treatment.Summary and conclusionPatients with underlying haematologic disorders sometimes cannot receive platinum-based chemotherapy due to its haematotoxicity, raising the need for alternative treatments for recurrent high-grade ovarian cancer. Data from clinical trials, supported by our case, suggest that mirvetuximab soravtansine may provide a promising option, allowing durable response without worsening pre-existing thrombocytopenia.

BACKGROUND:Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies. The resulting activation of the immune system may lead to neurological immune-related adverse events (n-irAEs). Here, we retrospectively characterized severe n-irAEs in a monocentric cohort. METHODS:We screened an in-house registry of the Medical University of Vienna, Austria, including all patients treated with ICIs between 2007 and 2023. Patients who underwent a neurological evaluation were identified, and their medical records were reviewed. Cases with severe (i.e., grade ≥ 3) n-irAEs were analyzed. We report clinical and demographic characteristics, neurological manifestations, treatment and outcomes. RESULTS:Ten out of 2043 screened patients (i.e., 0.5%) developed severe n-irAEs. In most cases (n = 7), neurological manifestations involved the neuromuscular system and/or peripheral nerves, including myasthenia/myositis (n = 5), polyneuropathy (n = 1), and facial nerve palsy (n = 1). Central nervous system involvement included aseptic meningitis, myelitis, and stroke (each n = 1). The number of ICI cycles prior to n-irAE onset varied, with a median of 3 cycles (range 1-43). The median time from the last infusion to symptom onset was 7 days (range 2-24). n-irAEs led to ICI discontinuation and/or immunomodulatory treatments in 9 patients. Clinical improvement was observed in 7 of 10 cases. No deaths were attributed to ICI-related toxicity. CONCLUSION:Our findings indicate that severe n-irAEs are rare. Nonetheless, clinicians should remain vigilant for delayed-onset neurotoxicity, even after long treatment exposure. Most patients showed clinical improvement following ICI discontinuation and/or immunomodulatory treatments.

The scavenger receptor CD36 has gained increasing interest in cancer research, with various functions in cell metabolism, angiogenesis, and immune response. This study aimed to investigate the molecular role of CD36 expression on tumor vasculature of advanced high-grade serous ovarian cancer (HGSOC) tissues and its prognostic implication. Immunohistochemical staining for CD36 was performed on whole tissue slides of 109 patients with advanced HGSOC. Patients were divided into two groups based on CD36 expression, i.e. positive versus negative, and correlated to clinicopathologic and survival data. RNA sequencing, metabolomics, and proteomics data were correlated to the CD36 expression within a subpopulation. CD36 expression in tumor vasculature was significantly associated with unfavorable overall survival (OS), both in univariate (HR 1.71, p = 0.039) and multiple Cox regression analyses (HR 1.91, p = 0.021), considering age, FIGO stage, postoperative residual tumor, and bevacizumab treatment as covariates. Positive CD36 expression was significantly associated with postoperative residual tumor, reflecting high tumor-burden. (p = 0.042). RNA sequencing from isolated tumor cells revealed an activated 'regulation of lipolysis in adipocytes' pathway significantly associated with CD36 expression. Co-association gene expression network analysis revealed increased ribosomal activity and protein translation in tumor cells of CD36-positive samples. Proteomics analysis of ascites showed three overexpressed proteins involved in lipid metabolism (LCN2, CFHR1, and CFHR4) out of 21 significantly deregulated proteins. Metabolomic analyses of serum showed a significant decrease of 60 glycerophospholipids (mainly unsaturated ones) and eight amino acids, four essential proteinogenic, in patients with CD36 positive vessels. CD36 intratumoral vessel expression was associated with unfavorable OS in patients with advanced HGSOC. Our analyses support the role of CD36 in tumor metabolism, possibly via CD36+-endothelial cell-mediated glycerophospholipid/oxLDL uptake. Signs of increased tumor metabolism were found, as well as a decrease of specific metabolic building blocks, indicating a higher-presumably CD36-mediated-uptake capacity.

BACKGROUND:It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. PRIMARY OBJECTIVE:Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. STUDY HYPOTHESIS:We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. TRIAL DESIGN:This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. MAJOR INCLUSION/EXCLUSION CRITERIA:We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. PRIMARY END POINT:The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. SAMPLE SIZE:With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. TRIAL REGISTRATION:ClinicalTrials.gov: NCT06689956.

In recent years, several randomized controlled trials have been published regarding cervical cancer therapy and significantly changed the treatment landscape. Recent advances have improved the treatment options and allow personalized treatment concepts with escalation of treatment in high-risk disease and de-escalation with reduction in morbidity in selected low-risk patients. This review aims to provide a comprehensive analysis of the latest landmark studies that are poised to significantly influence clinical practice. Personalized treatment concepts with careful patient selection allow de-escalation in the surgical treatment of cervical cancer. In low-risk cervical cancer patients (lesions of ≤2 cm with limited stromal invasion), simple hysterectomy (SH) was non-inferior to radical hysterectomy in terms of 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention and improved sexual health and quality of life. Furthermore, sentinel lymphadenectomy is constantly replacing systematic pelvic lymphadenectomy in patients with low-risk cervical cancer. In addition, further studies are necessary to clarify the role of postoperative therapy for patients with intermediate-risk cervical cancer. Starting in 2008, the EMBRACE studies assess the role of Image guided adaptive brachytherapy (IGABT) in LACC in addition to modern external beam radiotherapy concurrent to chemotherapy. The publication of the results of the EMBRACE I prospective study established MRI guided IGABT as state-of-the-art brachytherapy for LACC. EMBRACE II and additional prospective studies emerging from this consortium will address important questions in modern radiotherapy for LACC. Immune checkpoint inhibitors (CPIs) have been evaluated across various clinical settings and are expected to be utilized in numerous scenarios due to several positive randomized trials. Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens—neoadjuvant chemotherapy and adjuvant CPI therapy—have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer.

BACKGROUND:SHAPE demonstrated that simple hysterectomy was not inferior to radical hysterectomy in patients with low-risk cervical cancer. To further understand the role of preoperative LEEP/conization, clear LEEP/conization margins and surgical approach, analyses were performed regarding patterns of recurrence and death. PATIENTS AND METHODS:Outcomes (pelvic recurrence, extrapelvic recurrence and cervical cancer-related death) by surgical approach (minimally invasive surgery [MIS] vs. open), LEEP/conization (yes vs. no, involved vs. negative margins) and residual disease in the hysterectomy specimen (yes vs. no) are described with 3-year outcome rate estimated by Kaplan-Meier method and compared by Cox models. RESULTS:With a median follow-up of 4.5 years, 25 (3.7%) recurrences (pelvic or extrapelvic) were observed from 680 patients who underwent simple (338) or radical (342) hysterectomy. At surgeons' discretion, MIS was performed in 524 (77%) and open surgery in 156 (23%). Overall, 19 recurrences occurred following MIS (3.6%) and 6 following open surgery (3.8%). Among 174 patients with clear margins after LEEP/conization, 2 (1.4%) developed pelvic recurrences after MIS and none after open surgery. Among the entire cohort, 9 patients had extrapelvic recurrence, 7/524 (1.3%) following MIS and 2/156 (1.3%) following open surgery. However, no extrapelvic recurrence occurred after either MIS or open surgery among patients who had pre-hysterectomy LEEP/conization with clear margins. With regards to cervical cancer-related deaths, all occurred after MIS (5/524, 0.95%) and none after open surgery or after previous LEEP/conization with clear margins. CONCLUSIONS:Similar rates of recurrence and death were observed between patients who underwent MIS and open surgery within the SHAPE cohort. No extrapelvic recurrences and death occurred in patients with clear margins following prior LEEP/conization, regardless of surgical approach. The concept of pre-hysterectomy LEEP/conization might help to triage the most effective surgical strategy in terms of surgical approach and radicality in low-risk cervical cancer patients to ensure safe outcomes.