Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 Pathway in Advanced, Recurrent Endometrial Cancer: A Scoping Review with SWOT Analysis.

Results of recent clinical trials using the immune check point inhibitors (ICI) pembrolizumab or dostarlimab with/without lenvatinib has led to their approval for specific molecular subgroups of advanced recurrent endometrial cancer (EC). Herein, we summarise the clinical data leading to this first tissue-agnostic approval. As this novel therapy is not yet available in the United Kingdom standard care setting, we explore the strengths, weaknesses, opportunities, and threats (SWOT) of ICI treatment in EC. Major databases were searched focusing on clinical trials using programmed cell death protein 1 (PD-1) and its ligand (PD-L1) ICI which ultimately contributed to anti-PD-1 approval in EC. We performed a data quality assessment, reviewing survival and safety analysis. We included 15 studies involving 1609 EC patients: 458 with mismatch repair deficiency (MMRd)/microsatellite instability-high (MSI-H) status and 1084 with mismatch repair proficiency/microsatellite stable (MMRp/MSS) status. Pembrolizumab/dostarlimab have been approved for MMRd ECs, with the addition of lenvatinib for MMRp cases in the recurrent setting. Future efforts will focus on the pathological assessment of biomarkers to determine molecular phenotypes that correlate with response or resistance to ICI in order to identify patients most likely to benefit from this treatment.

Patient-initiated follow-up of early endometrial cancer: a potential to improve post-treatment cardiovascular risk?

PURPOSE: Is patient-initiated follow-up, post-surgical treatment of early endometrial cancer safe and can it be used holistically to improve cardiovascular health? What are the cost implications of this model of follow-up? METHODS: Retrospective data of 98 patients discharged to patient-initiated scheme since 2012. Service evaluation by anonymous patient feedback including physical health effects of the programme including weight loss. Financial cost was compared to traditional hospital-based follow-up over five years. RESULTS: No evidence of recurrence over 54 months median follow-up in low-risk endometrioid endometrial cancer. Patient feedback indicates that the exercise course helped women reduce their BMI. Over one third women felt happier and one fifth felt more confident and had a better ability to cope with stress. Total of 91% patients would recommend this model of follow-up to friends or family in the same circumstance. European Society for Medical Oncology guidance suggests the number of hospital-based follow-up appointments required for this cohort would cost £109,760. Calculations in this paper examine the cost of patient-initiated follow-up and reflect an overall saving of around 96.5%. CONCLUSION: This service evaluation supports the claim that patient-initiated follow-up represents a safe alternative to the traditional hospital-based protocol. There is a potential for additional services to be offered to encourage and promote a healthy lifestyle linked to improving quality of life and cardiovascular survival following surgery for endometrial cancer. IMPLICATIONS FOR CANCER SURVIVORS: Cardiovascular morbidity is the most common cause of death in endometrial cancer survivors. Incorporating an exercise course as part of routine follow-up can help reduce this risk. The friendships formed by this communal follow-up can contribute towards emotional health and recovery. This holistic approach should be incorporated into novel follow-up strategies to help reduce patient BMI and reduce cardiovascular risk.

Barriers to Immunotherapy in Ovarian Cancer: Metabolic, Genomic, and Immune Perturbations in the Tumour Microenvironment.

A lack of explicit early clinical signs and effective screening measures mean that ovarian cancer (OC) often presents as advanced, incurable disease. While conventional treatment combines maximal cytoreductive surgery and platinum-based chemotherapy, patients frequently develop chemoresistance and disease recurrence. The clinical application of immune checkpoint blockade (ICB) aims to restore anti-cancer T-cell function in the tumour microenvironment (TME). Disappointingly, even though tumour infiltrating lymphocytes are associated with superior survival in OC, ICB has offered limited therapeutic benefits. Herein, we discuss specific TME features that prevent ICB from reaching its full potential, focussing in particular on the challenges created by immune, genomic and metabolic alterations. We explore both recent and current therapeutic strategies aiming to overcome these hurdles, including the synergistic effect of combination treatments with immune-based strategies and review the status quo of current clinical trials aiming to maximise the success of immunotherapy in OC.

The Uncertain Benefit of Adjuvant Chemotherapy in Advanced Low-Grade Serous Ovarian Cancer and the Pivotal Role of Surgical Cytoreduction.

In our center, adjuvant chemotherapy is routinely offered in high-grade serous ovarian cancer (HGSOC) patients but less commonly as a standard treatment in low-grade serous ovarian cancer (LGSOC) patients. This study evaluates the efficacy of this paradigm by analysing survival outcomes and by comparing the influence of different clinical and surgical characteristics between women with advanced LGSOC (n = 37) and advanced HGSOC (n = 300). Multivariate analysis was used to identify independent prognostic features for survival in LGSOC and HGSOC. Adjuvant chemotherapy was given in 99.7% of HGSOC patients versus in 27% of LGSOC (p < 0.0001). The LGSOC patients had greater surgical complexity scores (p < 0.0001), more frequent postoperative ICU/HDU admissions (p = 0.0002), and higher peri-/post-operative morbidity (p < 0.0001) compared to the HGSOC patients. The 5-year OS and progression-free survival (PFS) was 30% and 13% for HGSOC versus 57% and 21.6% for LGSOC, p = 0.016 and p = 0.044, respectively. Surgical complexity (HR 5.3, 95%CI 1.2-22.8, p = 0.024) and complete cytoreduction (HR 62.4, 95% CI 6.8-567.9, p < 0.001) were independent prognostic features for OS in LGSOC. This study demonstrates no clear significant survival advantage of chemotherapy in LGSOC. It highlights the substantial survival benefit of dynamic multi-visceral surgery to achieve complete cytoreduction as the primary treatment for LGSOC patients.