The outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without indication for immune checkpoint inhibitors: the comparative study.

OBJECTIVE: Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI. METHODS: Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained. RESULTS: There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P < 0.05). No difference was observed in the occurrence of adverse events between patients receiving the two different treatments (all P > 0.05). CONCLUSION: First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients.

3D-printed individual template brachytherapy for the treatment of intractable central pelvic recurrent cervical cancer: A single institution experience.

OBJECTIVE: The prognosis of recurrent cervical cancer tends to be poor and there are limited effective treatments currently available for these patients. This study was developed to find a safe and effective treatment for patients with central pelvic recurrent cervical cancer. MATERIALS AND METHODS: This retrospective study analyzed patients with central pelvic recurrent cervical cancer who received 3D-printed individual template (3D-PIT) brachytherapy between February 2019 and June 2023. Analyses of dosimetric parameters, toxicity-related complications, and survival were conducted based on the data of these patients. RESULTS: Twenty-one patients with central pelvic recurrent cervical cancer patients were enrolled. All of them received 3D-printed individual template (3D-PIT) brachytherapy. The mean respective adjusted cumulative HRCTV-D90 and HRCTV-D98 values for these patients were 86.9 Gy and 75.4 Gy. And the local control (LC) rate of these patients was 57.1%. In these 21 patients, only 2 (9.5%) of them experienced grade 3-4 rectal adverse reactions, while 7 (33.3%) patients experienced grade 3-4 bladder adverse reactions. 5(23.8%) patients had fistula, while 3 of these 5 patients had undergone prior anti-VEGF targeted drug treatment which is a risk factor of fistula. The respective 2-year rates of overall and progression-free survival (OS and PFS) for these patients were 72.9% and 57.4%, with a 26-month median PFS. CONCLUSIONS: These single-institution data highlight the potential viability of 3D-PIT brachytherapy as an approach to managing intractable central pelvic recurrent cervical cancer following first-line treatment.

Discrepancy in PD-L1 expression between primary and metastatic tumors in two patients with recurrent cervical cancer.

Introduction: Pembrolizumab is an immunotherapy approved for use in patients with a combined positive score (CPS) greater than one with recurrent cervical cancer. In clinical practice, the CPS score is not typically analyzed in both primary and metastatic specimens. Case descriptions: Case 1A 42-year-old woman with history of an abnormal pap smears who presented with a large pelvic mass with initial biopsy of cervix demonstrating squamous cell carcinoma with negative PDL1 expression and a CPS score of 0. She underwent chemoradiation and presented three months after primary treatment completion with recurrence of squamous cell carcinoma and positive PD-L1 expression with a CPS score of 20. Pembrolizumab was added to cycle three of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She had progression on this regimen and was transitioned to tisotumab vedotin; however, ultimately opted to proceed with hospice secondary to failure to thrive.Case 2A 36-year-old woman with history of an abnormal pap smear in pregnancy and initial biopsy demonstrating endocervical adenocarcinoma, mucinous type. She underwent open radical hysterectomy, bilateral salpingectomy, bilateral oophorepexy, and bilateral pelvic lymph node dissection with subsequent adjuvant chemoradiation. Her initial pathology demonstrated positive PDL1 expression with CPS score of 15. She presented six months after completion of primary treatment with recurrence of endocervical adenocarcinoma, mucinous type and negative PD-L1 expression with a CPS score of < 1. Regardless of this discrepancy, pembrolizumab was added to cycle five of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She initially demonstrated a mixed response; however, ultimately progressed after eight cycles and was transitioned to tisotumab vedotin. Discussion: To our knowledge, discrepancies in PD-L1 expression in a matched setting between primary and metastatic tumors has only been reported once. This is the first case report describing these inconsistencies. Etiologies of and outcomes related to the discrepant expression of PD-L1 should be further studied.

Adjuvant Hysterectomy in Patients After Radiation for Locally Advanced Cervical Cancer: A Single-Center Prospective Longitudinal Study.

Introduction: Residual or recurrent cervical cancer post-CCRT is a challenging clinical issue, even though there has been much effort in recent decades to increase patient survival after radiation. There is a paucity of literature regarding the role of hysterectomy in recurrent/residual disease after radiation in LACC patients. Such a procedure is controversial and not routinely performed because of difficulties in obtaining tumor-free margins and the high rate of associated morbidity. Aims and Objectives: Evaluate outcomes and morbidities in patients who had undergone hysterectomy for residual or recurrent disease after radiation in LACC patients. Material and Methods: This is a prospective observational study on radiotherapy-treated LACC patients (IIB-III) with residual disease or recurrent disease who have undergone adjuvant hysterectomy. This study has been conducted at AHPGIC, Cuttack, with a sample size of 30 patients. Results: 18/30 patients underwent extrafascial hysterectomy, and rest 12 patients had radical hysterectomy. No significant difference in complications, achieving tumor free margins or recurrences post adjuvant hysterectomy based on the radicality of surgery was observed. 5 cases of recurrences post-adjuvant hysterectomy were detected. Some of the factors which had significant association with recurrences post adjuvant hysterectomy were non squamous histology, no preoperative brachytherapy, deep stromal invasion and positive surgical margins. Median follow-up time was 14 months (12-27 months). Conclusion: This study shows that adjuvant hysterectomy is feasible with good outcome and acceptable morbidity after chemoradiotherapy in cervical cancer patients "If selection of patients for adjuvant hysterectomy is appropriate."

Efficacy and Safety of 125I Seed Implantation in the Treatment of Pelvic Recurrent Cervical Cancer Following Radiotherapy: A Single-Arm Meta-Analysis of Chinese Patients.

BACKGROUND: The study aimed to assess the efficacy and safety of 125I seed implantation in the treatment of pelvic recurrent cervical cancer following radiotherapy. This meta-analysis was registered in PROSPERO. We looked up relevant studies in the databases of CNKI, Wanfang, CBM, PubMed, Embase, Cochrane Library, and Web of Science. The endpoint measures include the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. RECENT FIDINGS: The meta-analysis included six studies and a total of 246 patients. The pooled ORR of tumor response was 63%, and the DCR was 87%. The median PFS was 9.09 months, and the median OS was 13.46 months. The incidence of adverse events of Grade ≥III was 6%. CONCLUSION: In conclusion, this meta-analysis confirmed that 125I seed implantation has a good local control rate and high safety in the treatment of pelvic recurrent cervical cancer following radiotherapy, and can be used as a remedial treatment for pelvic recurrent cervical cancer following radiotherapy to prolong the survival time of patients. TRIAL REGISTRATION: PROSPERO: CRD42023423857.

Nab-paclitaxel plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer.

PURPOSE: This study aimed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer. METHODS: Between October 2020 and March 2022, consecutive patients with diagnosed with metastatic or recurrent cervical cancer were retrospectively recruited in our hospital. Fifty-four patients were treated with nab-paclitaxel plus cisplatin or carboplatin. Twenty-four patients were treated with paclitaxel plus cisplatin or carboplatin. A propensity score matching (PSM) analysis was done using a multivariable logistic regression model. The two groups were compared for objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the raw and matched dataset. RESULTS: The nab-paclitaxel group showed a higher ORR than the paclitaxel group both in the raw dataset (72.2% vs. 45.8%; P = 0.025) and matched dataset (81.1% vs. 47.6%; P = 0.008). The median PFS was significantly longer in the nab-paclitaxel group than in the paclitaxel group both in the raw and matched dataset (12 vs. 7 months; P < 0.05). The median OS was not reached in the nab-paclitaxel group compared with 15 months in the paclitaxel group, with a trend toward prolongation. The most common toxicity was hematological adverse events, including grade 3-4 neutropenia, grade 3 anemia and thrombocytopenia in both groups and no statistical differences were observed between the groups (all P > 0.05). CONCLUSION: Compared with paclitaxel plus platinum, nab-paclitaxel plus platinum may be an effective and tolerable option as first-line therapy for patients with metastatic or recurrent cervical cancer.

Case report: A case of recurrent cervical cancer with bronchial and esophageal metastases presenting with hemoptysis and dysphagia.

Background: The treatment outcomes and prognosis for recurrent cervical cancer are generally poor, with a 5-year survival rate of only 10%-20%. Case presentation: In this case, the patient is a young woman who experienced a recurrence 5 years after the initial treatment of cervical cancer. Her primary symptoms were hemoptysis and dysphagia, indicative of hilar and mediastinal lymph node metastases, with further involvement of the bronchus and esophagus. Additionally, the patient also presented with tumor-associated dermatomyositis. Following combined treatment with albumin-bound paclitaxel, carboplatin, bevacizumab, and cadonilimab, the patient's tumor was effectively controlled.

The Role of Pelvic Exenteration in Cervical Cancer: A Review of the Literature.

Pelvic exenteration represents a radical procedure aimed at achieving complete tumor resection with negative margins. Although it is the only therapeutic option for some cases of advanced tumors, it is associated with several perioperative complications. We believe that careful patient selection is related to better oncologic outcomes and lower complication rates. The objectives of this review are to identify the most current indications for this intervention, suggest criteria for case selection, evaluate recommendations for perioperative care, and review oncologic outcomes and potential associated complications. To this end, an analysis of English language articles in PubMed was performed, searching for topics such as the indication for pelvic exenteration for recurrent gynecologic neoplasms selection of oncologic cases, the impact of tumor size and extent on oncologic outcomes, preoperative and postoperative surgical management, surgical complications, and outcomes of overall survival and recurrence-free survival.

Predicting the recurrence of usual-type cervical adenocarcinoma using a nomogram based on clinical and pathological factors: a retrospective observational study.

Background: Usual-type cervical adenocarcinoma is the most frequent type of adenocarcinoma, and its prevalence is increasing worldwide. Tumor recurrence is the leading cause of mortality; therefore, recognizing the risk factors for cervical cancer recurrence and providing effective therapy for recurrent cervical cancer are critical steps in increasing patient survival rates. This study aimed to retrospectively analyze the clinicopathological data of patients with usual-type cervical adenocarcinoma by combining the diagnosis and treatment records after the initial treatment and recurrence. Methods: We retrospectively analyzed patients diagnosed with usual-type cervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection at Shengjing Hospital of China Medical University between June 2013 and June 2022. We constructed a nomogram-based postoperative recurrence prediction model, internally evaluated its efficacy, and performed internal validation. Results: This study included 395 participants, including 87 individuals with recurrence. At a 7:3 ratio, the 395 patients were divided into two groups: a training set (n = 276) and a validation set (n = 119). The training set was subjected to univariate analysis, and the risk variables for recurrence included smoking, ovarian metastasis, International Federation of Gynaecology and Obstetrics (FIGO) staging, lymphovascular space invasion, perineural invasion, depth of muscular invasion, tumor size, lymph node metastasis, and postoperative HPV infection months. The aforementioned components were analyzed using logistic regression analysis, and the results showed that the postoperative HPV infection month, tumor size, perineural invasion, and FIGO stage were independent risk factors for postoperative recurrence (p<0.05). The aforementioned model was represented as a nomogram. The training and validation set consistency indices, calculated using the bootstrap method of internal validation, were 0.88 and 0.86, respectively. The model constructed in this study predicted the postoperative recurrence of usual-type cervical cancer, as indicated by the receiver operating characteristic curve. The model demonstrated good performance, as evidenced by the area under the curve, sensitivity, and specificity values of 0.90, 0.859, and 0.844, respectively. Conclusion: Based on the FIGO staging, peripheral nerve invasion, tumor size, and months of postoperative HPV infection, the predictive model and nomogram for postoperative recurrence of usual-type cervical adenocarcinoma are precise and effective. More extensive stratified evaluations of the risk of cervical adenocarcinoma recurrence are still required, as is a thorough assessment of postoperative recurrence in the future.

Dosimetric parameters and safety analysis of 3D-printing non-coplanar template-assisted interstitial brachytherapy for non-centrally recurrent cervical cancer.

Introduction: The prognosis of patients with non-central recurrent cervical cancer (NRCC) remains poor, and treatment options are limited. We aimed to explore the accuracy and safety of the 3D-printed non-coplanar template (3D-PNCT)-assisted 192Ir interstitial brachytherapy (ISBT) in the treatment of NRCC. Material and methods: A total of 36 patients with NRCC who received 3D-PNCT-guided 192Ir ISBT in the First Affiliated Hospital of Zhengzhou University from January 2021 to July 2022 were included in this study. There were 36 3D-PNCTs that were designed and printed. The prescribed dose was 30-36 Gy, divided into five to six times, once a week. To evaluate whether the actual parameters were consistent with the preoperative design, the dosimetric parameters of pre- and postoperative treatment plans were compared, including dose of 90% high-risk clinical target volume (HR-CTV D90), volume percentage of 100% and 150% prescribed dose V100% and V150%, homogeneity index (HI), conformal index (CI), external index (EI), and dose received by 2 cm3 (D2cm3) of the rectum, colon, bladder, and ileum. The safety parameters including occurrence of bleeding, infection, pain, radiation enteritis, and radiation cystitis within 3 months after operation were recorded. Results: All patients successfully completed the treatment and achieved the goals of the preoperative plan. There was no significant difference in the accuracy (HRCTVD90, V100%, EI, CI, and HI) and safety (D2cm3 of rectum, colon, bladder, and ileum) parameters of the postoperative plan compared with the preoperative plan (all p>0.05). Major side effects included bleeding at the puncture site (13.9%), postoperative pain (8.3%), acute radiation cystitis (13.9%), and radiation enteritis (19.4%). There were no serious perioperative complications and no grade 3-4 acute radiotherapy side effects. Conclusion: 3D-PNCT-assisted 192Ir ISBT can be accurately and safely applied in the treatment of patients with NRCC.

Recurred Uterine Cervical Cancer Initially Manifesting as Hemorrhagic Cyst: A Case Report Recurred Uterine Cervical Cancer Initially Manifesting.

BACKGROUND: Recurrence of uterine cervical cancer is common and often shows a dismal prognosis. Local recurrence usually manifests as solid soft tissue lesions and has rarely been reported to have cystic lesions. CASE PRESENTATION: Herein, we report a case of recurrent uterine cervical cancer with initial manifestation as a hemorrhagic cyst, assessed using strain sonoelastography, CT, and MRI. CONCLUSION: Although cystic recurrence is uncommon, newly detected simple or complex cystic lesions should be closely monitored.

Transperineal endoscopic approach with GelPOINT V-path in laparoscopic pelvic exenteration for postirradiated recurrent cervical cancer.

Pelvic exenteration (PE) is a highly invasive procedure associated with high morbidity and mortality rates. Laparoscopy is a promising option to reduce this invasiveness, and laparoscopic PE significantly reduces blood loss and shortens hospital stays. In the case of a large tumor with invasion to the surrounding organs, laparoscopic dissection around the pelvic floor is sometimes problematic owing to restrictions on handling instruments. To overcome these limitations, we performed a transperineal endoscopic approach using the GelPOINT V-path in addition to laparoscopic PE. This approach enabled dissection around the pelvic floor without the abovementioned obstacles under magnified visualization. As a result, we could dissect the pelvic floor precisely with a reduction of the dead pelvic space, which might contribute to reduced rates of postoperative complications while ensuring oncologic outcomes.

KORTUC, a novel hydrogen peroxide­based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer.

Kochi Oxydol Radiation Therapy for Unresectable Carcinoma (KORTUC) is a novel radiosensitizer invented by Professor Ogawa at Kochi University (Japan) in 2006. The current study aimed to report the experience of the present authors with the use of KORTUC treatment in combination with interstitial brachytherapy (ISBT), with or without external beam (EB) radiotherapy (RT), in patients with locally recurrent cervical cancer (LRCC), who were likely to have a high risk of poor prognosis. Between April 2012 and January 2020, 14 female patients (15 tumoral lesions) with LRCC underwent KORTUC with ISBT. Their previous treatments included surgery (n=4), radiation therapy (n=8) and surgery plus RT (n=3). The primary lesions were located in the vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2) and lymph nodes (n=2). At 2 h before RT, KORTUC was injected intratumorally via direct colposcopy. The dose of KORTUC ranged from 4-12 ml, adjusted for the tumor size. For patients who underwent ISBT, KORTUC was administered before and after insertion of the applicator before irradiation. Intratumoral injection of KORTUC was completed without any technical or safety issues in all 15 patients; it was well tolerated with no adverse events observed. KORTUC also showed preferable efficacy; a clinical complete response was observed in 87% of patients and the initial response rate was 100%. The 2-year local control rate in patients who underwent ISBT + KORTUC was 79%, whereas it was 63% in the re-irradiation group which was significantly lower (P=0.02) than that in the non-irradiation group (100%). Based on this finding, KORTUC with external irradiation is considered to be an optimal treatment strategy for patients with newly diagnosed LRCC this disease. Additionally, KORTUC may be an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Efficacy and safety of intensity Modulated Radiation therapy combined with Concurrent Chemoradiotherapy in the treatment of Recurrent Cervical Cancer.

Objective: To evaluate the clinical value of intensity modulated radiation therapy (IMRT) combined with concurrent chemoradiotherapy in the treatment of recurrent cervical cancer. Methods: This was a retrospective study. Eighty patients with recurrent cervical cancer were recruited and randomly divided into two groups: the experimental group and the control group, with 40 cases in each group at The Fourth Hospital of Hebei Medical University from April, 2017 to April, 2022. Patients in the control group were only given IMRT, while those in the experimental group were given concurrent chemoradiotherapy with paclitaxel and cisplatin based on IMRT. All patients were evaluated for clinical efficacy, adverse drug reactions, and differences in the levels of SCC-Ag, CEA and CA724 and other tumor markers before and after treatment. Results: The total effective rate in the experimental group was significantly better than in the control group (p=0.02). The incidence of adverse reactions was 40% in the experimental group and 32.5% in the control group, with no statistically significant difference (p=0.48). After treatment, the levels of tumor markers in the experimental group were significantly lower than those in the control group, with a statistically significant difference (p=0.00). The three years survival rate was 80% in the experimental group and 55% in the control group (p=0.03). The five years survival rate was 65% in the experimental group and 42.5% in the control group, with a statistically significant difference (p=0.04). Conclusion: Intensity modulated radiation therapy (IMRT) combined with concurrent chemoradiotherapy is a safe and effective regimen for recurrent cervical cancer, boasting significant clinical efficacy, reduced tumor markers, no significant increase in adverse reactions, and significantly improved three-years and five years survival rate.

Penpulimab and anlotinib in an elderly patient with recurrent cervical cancer: a case report and literature review.

We present a case of a 76-year-old patient with recurrent cervical cancer who underwent first-line treatment with penpulimab combined with anlotinib. The patient was diagnosed with poorly differentiated stage III C1r cervical squamous cell carcinoma and received standard cisplatin-sensitized chemoradiotherapy, subsequently achieving a good treatment effect of complete response. Recurrence occurred nearly 14 months after treatment, with multiple metastases including in the brain and lung. Oral anlotinib was less effective, but the treatment of penpulimab combined with anlotinib showed an obvious curative effect. It has been maintained for more than 17 months, and as of April 2023 the patient is still maintaining her response. Our case suggests that penpulimab combined with anlotinib has promising efficacy in the treatment of elderly patients with recurrent cervical cancer.

A 76-year-old female patient was diagnosed with cervical cancer. She received a type of treatment called chemoradiotherapy, which helped her get better. However, after 14 months of treatment, the cancer came back and spread to other parts of the body including the brain and lungs. She was given a medicine called anlotinib, which did not work very well. Then she received two medications at the same time, penpulimab and anlotinib, which worked better. Her cancer went away completely and has stayed this way for 17 months. This case shows that the combination of penpulimab and anlotinib can help treat older people with cervical cancer that comes back.

Cemiplimab as Second-Line Therapy for Patients with Recurrent Cervical Cancer: A United States-based Cost-effectiveness Analysis.

INTRODUCTION: The efficacy of cemiplimab in recurrent cervical cancer has been demonstrated in the clinical trial EMPOWER-Cervical 1. However, its high price makes patients and clinicians hesitate to use it. Therefore, we designed a study to evaluate its cost-effectiveness. METHODS: We developed a Markov model based on phase III clinical trials to calculate the cost, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over 20 years with a willingness-to-pay (WTP) threshold of $150,000/QALY. The economic data included were obtained from official US government websites and published literature. Sensitivity analysis was used to determine the uncertainties associated with the model, and a subgroup analysis was performed. RESULTS: Compared with chemotherapy, cemiplimab produced an additional 0.597 QALYs (0.751 LYs), resulting in an ICER of $111,211.471/QALY in the United States. The cost of cemiplimab is the most influential factor in the model. The results of these models were robust in all sensitivity analyses. From the American public payers' perspective, subgroup analysis showed cemiplimab was a cost-effective regimen in patients with squamous cell carcinoma, adenocarcinoma, or programmed cell death ligand 1 (PD-L1) ≥ 1%. CONCLUSION: From the American public payers' perspective, cemiplimab is a cost-effective treatment option for second-line treatment of recurrent cervical cancer. Meanwhile, cemiplimab was a cost-effective treatment for patients with PD-L1 ≥ 1 and all histological types.

Predictors of Oncologic Outcome in Patients Receiving Phase I Investigational Therapy for Recurrent or Metastatic Cervical Cancer.

Introduction: We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials. Methods: Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed. Results: We included 65 patients with a median age of 41 years (range, 20-74), 3 prior therapies (range, 1-7), and 67.7% squamous carcinoma. The rate of distant metastasis at trial entry was 84.6%. The most common molecular alterations included PIK3CA (46.5%), PD-L1+ (46.2%), EPH (30.0%), and CREBBP (23.1%); 23.1% had received a prior checkpoint inhibitor. Phase I trials were for immunotherapy (58.5%) or targeted therapy (41.5%). The rate of biomarker matching was 21.5%. For all patients, median PFS was 3.6 months (95% CI, 2.0-5.2) and OS was 9.3 months (95% CI, 7.0-10.6). Factors at study entry associated with worse survival were presence of bone metastasis (PFS 1.6 vs 4.4 months: hazard ratio [HR], 2.8; p = 0.001; OS 3.8 vs 10.0 months: HR, 3.9; p < 0.0001) and absolute lymphocyte count below 1000/µL (PFS 1.8 vs 5.2 months: HR, 2.9; p = 0.0004; OS 7.0 vs 10.6 months: HR, 3.2; p = 0.0009). Factors associated only with worse OS were absolute neutrophil count above 4700/µL, hemoglobin below 10.5 g/dL, and smoking status. Grade 3+ treatment-related adverse events were seen in 16.9% of cases. Conclusion: Bone metastasis and absolute lymphocyte count below normal range at phase I study entry portend poor survival in patients with recurrent or metastatic cervical cancer.

Investigational drugs for recurrent or primary advanced metastatic cervical cancer: what is in the clinical development pipeline?

INTRODUCTION: Recurrent or primary advanced metastatic cervical cancer (R/M CC) has a poor prognosis with a 5-year-survival rate of 16.5%, demanding novel and improved therapies for the treatment of these patients. The first-line standard of care for R/M CC now benefits from the addition of the immune checkpoint inhibitor, pembrolizumab, to platinum-based chemotherapy with paclitaxel and bevacizumab. Additionally, new options for second-line treatment have become available in recent years. AREAS COVERED: Here, we review current investigational drugs and discuss their relative targets, efficacies, and potential within the R/M CC treatment landscape. This review will focus on recently published data and key ongoing clinical trials in patients with R/M CC, covering multiple modes of action, including immunotherapies, antibody-drug conjugates, and tyrosine kinase inhibitors. We searched clinicaltrials.gov for ongoing trials and pubmed.ncbi.nih.gov for recently published trial data, as well as recent years' proceedings from the annual conferences of the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO), and the International Gynecologic Cancer Society (IGCS). EXPERT OPINION: Therapeutics currently attracting attention include novel immune checkpoint inhibitors, therapeutic vaccinations, antibody-drug conjugates, such as tisotumab vedotin, tyrosine kinase inhibitors targeting HER2, and multitarget synergistic combinations.

Impact of lymphadenectomy in patients with locally recurrent or persistent cervical cancer treated with salvage hysterectomy.

AIM: To investigate the role of lymphadenectomy (LND) in locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy. METHODS: Locally recurrent or persistent cervical cancer patients treated with salvage hysterectomy, with or without LND, were identified. Patients were divided into two groups according to the status of radiologic evidence of lymph node metastasis, and the impact of LND was investigated by evaluating postoperative survival. RESULTS: This study included 72 patients; 48 did not show radiological evidence of lymph node metastasis (Group 1) while 24 did (Group 2). Overall, the addition of LND to salvage hysterectomy resulted in increased postoperative complications. In Group 1, salvage hysterectomy plus LND resulted in the identification of five cases with false-negative lymph nodes (19.2%), but showed no advantage over salvage hysterectomy alone in terms of postoperative survival. In Group 2, all patients underwent LND, which resulted in the identification of eight cases with false-positive nodes (33.3%), and reasonably long postoperative survival. The estimated 3-year postoperative survival rate in this group was 39.7%. CONCLUSION: Including LND in salvage hysterectomy allows for precise lymph node staging but increases risk of postoperative complications. However, considering the inability to improve survival, LND should not be performed during salvage hysterectomy in patients without radiological evidence of lymph node metastasis. In patients with radiological evidence of lymph node metastasis, salvage hysterectomy plus LND can only be performed in those who understand the risk of postoperative complications and the limited evidence supporting its survival advantage.

Pattern of Care of Recurrent Cervical Cancer in Low-resource Settings: Challenges and Patient-initiated Follow-up as a Novel Opportunity.

Introduction: The availability of optimum diagnostic strategies remains a major problem in resource-constraint countries. This technique of patient-initiated follow-up (PIFU) has been recently adopted in the UK for gynecological cancers and has proven cost benefits. However, no study from the Indian subcontinent has ever been reported. Aims and Objectives: The primary objective was to study the pattern of care of recurrent cervical cancer in low-resource settings. The secondary objective was to compare the reliability of symptomatology/clinical evaluation and imaging methods on follow-up to detect recurrence and thus explore the feasibility of symptom-based PIFU. Materials and Methods: This was a single-institutional retrospective analysis of recurrent cervical cancer cases for a period of 3 years from January 2019 to January 2022. Patients who followed up for minimum of 6 months were included in the study. Results: In 57 of the total 69 patients, symptoms alone were the index diagnostic method. Interestingly, neither of the methods of recurrence detection had impact on overall survival (OS). Cox regression analysis revealed adverse impact of erratic/lost to follow-up (hazard ratio [HR] = 3.8) and pelvic side wall disease (HR = 1.33) on survival. Patients with positive para-aortic nodes had significantly shorter disease-free interval of 11 months, so adding systemic therapy to adjuvant treatment in this cohort needs to be further investigated. Conclusion: Our analysis showed that patients with recurrence who were diagnosed with clinical manifestations alone vis-à-vis the ones who were diagnosed primarily on routine follow-up visit by some imaging or diagnostic test had comparable oncologic outcomes. PIFU can be a "practice changing modality" in patient management system, especially in low-resource settings. It will prove to be a simple cost-effective method to detect recurrence and prevent fallouts. Our study points to the feasibility of PIFU in Indian scenario.