Objective: Tumor immune microenvironmental features may predict survival and guide treatment. This study aimed to comprehensively decipher the immunological features of different molecular subtypes of endometrial cancer.Methods: In this retrospective study, 26 patients with primary endometrial cancer and four with recurrent disease treated in our center from December 2018 to November 2021 were included. Next-generation sequencing was performed on tumor samples. Patients were classified into four subtypes, including POLE mutant, microsatellite instability high (MSI-H), no specific molecular profile (NSMP) and TP53 mutant subtypes. Tumor-infiltrating immune cells were quantified using multiplex immunofluorescence assays.Results: Of the 26 primary endometrial cancer cases, three were POLE mutant, six were MSI-H, eight were NSMP and nine were TP53 mutant. Of the four recurrent cases, two belonged to the NSMP subtype and two belonged to the TP53 mutant subtype. The tumor mutation burden (TMB) levels of POLE mutant and MSI-H cases were significantly higher than that of the other two subtypes (p< 0.001). We combined POLE mutant and MSI-H subtypes into the TMB high (TMB-H) subtype. The TMB-H subtype showed a high degree of infiltration of CD8⁺ T cells. In the NSMP subtype, the overall degree of intra-tumoral infiltrating immune cells was low. In the TP53 mutant subtype, the densities of both PD-L1⁺ macrophages (p = 0.047) and PD-1⁺ T cells (p = 0.034) in tumor parenchyma were the highest among the four subtypes.Conclusion: Endometrial cancer of TMB-H, NSMP and TP53 mutant subtypes displayed phenotypes of normal immune response, absence of immune infiltration, and suppressed immune response, respectively. These features may provide mechanistic explanations for the differences in patients’ prognosis and efficacy of immune checkpoint blockade therapies among different endometrial cancer subtypes.

Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients. The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5–7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50–100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect. To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life. The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015.

Dai Y, et al. J Gynecol Oncol. 2019 Jun;31:e27. https://doi.org/10.3802/jgo.2020.31.e27

Objectives: Our study aimed to evaluate the quality of life (QoL) and pelvic floor function of cervical cancer (CC) patients after treatment. Design: This was a cross-sectional observational cohort study. Participants: The participants included in this study were CC patients who underwent radical hysterectomy (RH) from 2012 to 2018 at 18 medical centers across China. Methods: The validated versions of the Pelvic floor Distress Inventory-Short Form 20, Overactive Bladder Symptom Score, and Euro Qol Five-Dimension questionnaires were used to evaluate postoperative pelvic floor dysfunction (PFD) and QoL. Results: A total of 689 CC patients were enrolled. The incidence of stress urinary incontinence (SUI), incomplete urinary emptying, and constipation were 32.7, 27.7, and 28.6%, respectively. Multivariate analysis confirmed that laparoscopic RH (LRH) and vaginal wall resection greater than 3 cm were risk factors for lower urinary tract symptoms (LUTS). LRH and chemotherapy were risk factors for SUI. Chemoradiotherapy and LRH were risk factors for overactive bladder (OAB). A high body mass index and LRH were risk factors for more severe defecation symptoms. ARH and large amount of operative blood loss were risk factors for poor QoL. Conclusion: PFD is common in CC patients after treatment. LRH seems to increase the postoperative distress, including LUTS and defecation symptoms. Postoperative urinary incontinence and OAB are more bothersome for patients undergoing chemotherapy and radiotherapy. We recommend evaluating pelvic floor function as a standard assessment during follow-up.