Advanced, recurrent, and persistent cervical cancer management: in the era of immunotherapy.

Cervical cancer constitutes a significant health burden for women worldwide despite being preventable by vaccination and screening. Advanced stages of the disease are associated with a poor prognosis, and treatment approaches have seen little change over several decades, resulting in an overall survival rate of no more than 17 months. Additionally, there are limited options for second-line treatment. The urgent need for innovative and effective therapies to improve the outlook for this group of patients, along with an enhanced understanding of the interactions between the disease and the host's immune system, has propelled immunotherapy into a rapidly advancing field with notable achievements. Among various immunotherapeutic approaches, immune checkpoint inhibitors emerge as the most advanced treatment option. Clinical trials assessing these inhibitors as single agents or in combination with chemotherapy show promising results. As immunotherapy begins to redefine standards of care for metastatic, recurrent, or persistent cervical cancer, this review addresses recent advances and current recommendations for its management in both first and second-line treatment. The goal is to provide insights into the evolving landscape of cervical cancer treatment, specifically focusing on immunotherapeutic interventions.

State of the art of cervical cancer treatment in rare histologies.

The objective of this review is to summarize the current scientific evidence to formulate clinical recommendations regarding the classification, diagnostic approach, and treatment of rare histological subtypes of cervical cancer; neuroendocrine carcinoma, gastric-type mucinous adenocarcinoma, and glassy cell adenocarcinoma. These histological subtypes are generally characterized by their low frequency, aggressive biological behavior, certain chemoradioresistance, and consequently, high recurrence rates with a deleterious impact on survival. Molecular studies have identified several associated mutations in neuroendocrine carcinoma (PIK3CA, MYC, TP53, PTEN, ARID1A, KRAS, BRCA2) and gastric-type adenocarcinoma (KRAS, ARID1A, PTEN) that may serve as molecular targets. While adenocarcinomas are typically treated and classified based on squamous histology across early, locally advanced, and advanced stages, the treatment strategies for neuroendocrine carcinomas in early stages or locally advanced cases differ, particularly in the sequencing of administering chemotherapy, chemoradiotherapy, or surgery. The chemotherapy regimen is based on etoposide plus cisplatin (EP). Unlike squamous cell carcinomas, immune checkpoint inhibitors are yet to establish a standard role in the treatment of recurrent neuroendocrine carcinomas due to the absence of clinical trials. Regarding glassy cell adenocarcinomas and gastric-type adenocarcinoma, the potential use of immunotherapy in advanced stages/disease requires further evaluation through international collaborations, given the limited number of cases.

Chemoradiotherapy treatment with gemcitabine improves renal function in locally advanced cervical cancer patients with renal dysfunction.

BACKGROUND: Cervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. METHODS: This retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. RESULTS: 351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). CONCLUSION: CCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.