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Simple Summary: This systematic review was conducted using four public electronic databases (PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials) from the date of inception to 31 May 2023, and 10 original articles with information regarding neoadjuvant chemotherapy (NACT) for malignant ovarian germ cell tumors (MOGCT) were identified. The results of the meta-analysis showed that NACT was used in approximately 40% of advanced MOGCT cases, with a response rate of 95.8%. The uterine preservation rate was approximately 70%, and the cumulative resumed menstruation rate was 100% (n = 30). Four comparator studies evaluating NACT versus primary debulking surgery between the groups showed similar overall survival, disease-free survival, recurrence rate, and adverse event rate (grade 3–4) from chemotherapy. Although available data are limited and level I evidence is lacking, we believe that NACT may be feasible for advanced MOGCT. Further studies are required to confirm this study's results. Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15–5.27), comparable overall survival (n = 3; 87.0–100% versus 70.0–100%), disease-free survival (n = 3; 87.0–100% versus 70.0–100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38–32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients. [ABSTRACT FROM AUTHOR]

Simple Summary: To investigate the efficacy of minimally invasive surgery (MIS) in the treatment of uterine-confined and node-negative cervical cancer in Japan, we conducted a population-based study using Osaka Cancer Registry data ranging between 2011 and 2018. A total of 2279 patients who underwent surgical treatment for uterine-confined and node-negative cervical cancer were identified. The patients were classified into groups according to surgery type (open and MIS groups) and year of diagnosis (2011–2014 and 2015–2018), and their oncologic outcomes were compared between the MIS and open groups. In the analyses including all patients, i.e., patients diagnosed in 2011–2014 and those diagnosed in 2015–2018, there were no differences in overall survival between the MIS and open groups. Our population-based cohort study provides epidemiological evidence that MIS does not compromise survival outcomes when compared with conventional open surgery in Japanese patients with FIGO 2018 stage I cervical cancer. We aimed to compare the oncological outcomes between Japanese women with uterine-confined and node-negative cervical cancer who underwent open surgery and those who underwent minimally invasive surgery (MIS). A population-based retrospective cohort study was conducted using data from the Osaka Cancer Registry that ranged from 2011 to 2018. A total of 2279 patients who underwent surgical treatment for uterine-confined and node-negative cervical cancer were identified. The patients were classified into groups according to surgery type (open and MIS groups) and year of diagnosis (group one, 2011–2014; group two, 2015–2018). The oncologic outcomes were compared between the MIS and open groups. When the MIS group (n = 225) was compared with open group (n = 2054), overall, there was no significant between-group difference in terms of overall survival. Based on Kaplan–Meier estimates, the probability of overall survival at four years was 99.5% in the MIS group and 97.2% in the open group (p = 0.1110). When examined according to the year of diagnosis, there were no significant between-group differences in the overall survival in both groups one and two. In this population-based cohort study, MIS did not compromise survival outcomes when compared with conventional open surgery in Japanese patients with uterine-confined and node-negative (FIGO 2018 stage I) cervical cancer. [ABSTRACT FROM AUTHOR]

To investigate the prognostic significance of pretreatment C-reactive protein (CRP), albumin, and the CRP to albumin ratio (CRP/Alb) in epithelial ovarian cancer (EOC) patients. Clinical data from 308 EOC patients between April 2007 and March 2016 were collected and retrospectively reviewed. The cutoff values for CRP, albumin, and CRP/Alb were defined by receiver operating characteristics (ROC) analyses. Univariate or multivariate analysis was conducted to evaluate the prognostic significance of these factors for disease-specific survival. The cutoff values for CRP, albumin, and CRP/Alb were 0.76, 3.8, and 0.048 by ROC analysis, respectively. Cox regression analyses demonstrated that an elevated CRP/Alb is an independent predictor of short disease-specific survival irrespective of clinical stage or optimal surgery rate. When examined according to clinical stage, elevated CRP/Alb was associated with short disease-specific survival in both early-stage and advanced-stage patients. Cox regression analyses demonstrated that an elevated CRP, but not lower albumin, is also an independent predictor of short disease-specific survival. When two prognosticators were compared, CRP/Alb was found to be superior to CRP for predicting disease-specific survival in EOC patients. Pretreatment elevated CRP/Alb is a predictor of shorter survival in EOC patients regardless of clinical stage. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and toxicity of external beam radiotherapy (RT) for isolated recurrent epithelial ovarian cancer (EOC). Methods: Twenty‐four isolated recurrent EOC patients treated with RT at Osaka University Hospital between January 2000 and January 2017 were included in the current study. Data regarding the primary or recurrent diseases, follow‐up findings, and efficacy or toxicities of RT were collected and retrospectively analyzed. Survival rates were calculated using the Kaplan–Meier method and compared using the log‐rank test. Results: Their median age was 59 years. Most patients had International Federation of Gynecology and Obstetrics stage III‐IV diseases at the initial diagnosis. Histologically, serous adenocarcinoma was predominant, followed by clear cell adenocarcinoma. All patients had received at least one regimen of platinum‐based chemotherapy; 8 were platinum‐sensitive relapse and the others were platinum‐resistant. Lymph nodes were the most common sites of recurrence, and the median tumor size was 25.5 mm. The median total dose of RT administered was 54 Gy, with a median daily dose of 2 Gy. RT was well‐tolerated, and no patients experienced Grade 3/4 toxicities. The in‐field overall response rate was 58.3% (14/24), the median regression rate was −40.2% (range: −100 to 0) and the median survival period after RT was 17 months. The 1‐year survival and local progression‐free survival rates after RT were 66.7% and 45.8%, respectively. Conclusion: RT showed significant antitumor effect against isolated recurrent EOC without causing severe toxicities. Prospective studies with sufficient statistical power are warranted to further evaluate the role of RT in this patient population. [ABSTRACT FROM AUTHOR]

Aim To investigate the predictors of distant relapse in International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IVA cervical cancer patients treated with definitive radiotherapy (RT). Methods The clinical data of 219 patients with FIGO stage IIB-IVA cervical cancer treated with definitive RT between January 1997 and December 2011 were retrospectively reviewed. The cumulative distant relapse, progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was used to investigate the predictors of distant relapse in patients. Results Following treatment with definitive RT, 61 of the 219 (27.9%) patients developed distant relapse with median PFS and OS rates of 9.9 and 32.8 months, and estimated five-year PFS and OS rates of 4.9% and 21.3%, respectively. Multivariate analysis revealed that pelvic node metastasis, pretreatment leukocytosis and pretreatment neutrophilia were significant predictors of distant relapse. The risk of developing distant relapse was found to be associated with the number of predictors that the patients displayed: the estimated five-year distant relapse rates of the patients with no predictors, one predictor and two predictors were 20.3%, 35.5% and 88.9%, respectively. Conclusions Roughly 28% of patients with FIGO stage IIB-IVA cervical cancer developed distant relapse after definitive RT. Pelvic lymph node metastasis and pretreatment leukocytosis/neutrophilia are independent predictors of distant relapse. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of radical hysterectomy after radiotherapy (RH-AR) for recurrent or persistent cervical cancer.Methods: The present retrospective study included patients who underwent RH-AR for recurrent or persistent cervical cancer at Osaka University Hospital, Japan, between May 1, 2010 and September 30, 2016. Patient characteristics, intraoperative and postoperative adverse events, and surgical outcomes were investigated to identify patients at increased risk of recurrence or severe surgical adverse events.Results: There were 31 patients scheduled for treatment with RH-AR; one hysterectomy procedure was aborted. No intraoperative adverse events or treatment-related deaths occurred, and 8 (27%) patients experienced severe postoperative adverse events. After a median 34 months of follow-up, 13 (43%) patients had developed recurrent disease, predominantly at distant sites. The estimated 3-year overall survival rate was 53.8%. Positive surgical margins, nodal metastasis, parametrial invasion, and no adjuvant treatment after RH-AR were found to be predictors of increased risk of recurrence. No predictors of severe surgical adverse events were identified.Conclusion: RH-AR was a safe, curative treatment for patients with recurrent or persistent cervical cancer. However, considering the significant risk of surgical adverse events, RH-AR should only be performed for a select group of patients. [ABSTRACT FROM AUTHOR]

Background: There are no guidelines about the selection of recurrent cervical cancer patients for salvage surgery. Methods: Patients who developed recurrent or persistent cervical cancer in a previously irradiated field and were subsequently treated with salvage surgery (the surgery group) or palliative care alone (the palliative group) were identified. Patient characteristics, treatment-related complications, and survival were retrospectively compared between the two groups. Results: A total of 79 patients (surgery group, n = 51; palliative group, n = 28) were identified. In the surgery group, no intraoperative complications or treatment-related deaths occurred. Eleven patients (21.6%) experienced severe postoperative complications. After a median follow-up period of 41.5 months, 23 patients (45.1%) had developed recurrent disease, predominantly at distant sites, and 19 patients (37.3%) had died of disease progression. The estimated 3-year progression-free survival (PFS) and overall survival rates of the surgery group were 50.4 and 56.5%, respectively. In the palliative group, all of the patients died of disease progression. Positive surgical margins and lymph node metastasis were found to be independent prognostic factors for PFS in the surgery group. Among the patients with no or one poor prognostic factor, the patients in the surgery group survived significantly longer than those in the palliative group. However, among the patients with 2 poor prognostic factors, the surgery group and palliative group displayed similar survival periods. Conclusions: Salvage surgery is a curative treatment in recurrent or persistent cervical cancer patients. However, considering its high surgical complication rate, salvage surgery should only be offered to carefully selected patients. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the significance of adenocarcinoma (AC) compared with squamous cell carcinoma (SCC) with regard to the survival of surgically-treated early stage cervical cancer patients. Methods: We retrospectively reviewed the medical records of 520 patients with FIGO stage IA2–IIB cervical cancer who were treated with radical hysterectomy with or without adjuvant radiotherapy between January 1998 and December 2008. The patients were classified according to (i) pathological risk factors (low-, intermediate-, or high-risk group) and (ii) adjuvant radiotherapy (concurrent chemoradiotherapy [CCRT group] or radiotherapy alone [RT group]). Survival outcomes were examined by Kaplan–Meier method and compared with Log-rank test. Multivariate analysis for disease-specific survival (DSS) was performed using Cox proportional hazards regression model to investigate the prognostic significance of histological subtype. Results: AC histology was associated with significantly decreased DSS compared with SCC histology in the intermediate- and high-risk groups (hazard ratio: 3.06 and 2.88, respectively, both P<0.05) while there was no survival difference in the low-risk group (P=0.1). Among patients who received any types of adjuvant radiotherapy, DSS of AC histology patients were significantly poorer than SCC histology. Multivariate analysis demonstrated AC histology to be an independent predictor of decreased DSS in both CCRT and RT groups. Moreover, pelvic nodal metastasis significantly predicted the poor survival of patients with AC histology who received CCRT in multivariate analysis Conclusions: Adenocarcinoma is an independent prognostic indicator of poor survival in early stage cervical cancer patients with intermediate- and high-risk factors, regardless of the type of adjuvant radiotherapy after radical hysterectomy. [Copyright &y& Elsevier]

Purpose: We investigated the role of physical examination, CT scan, chest X-ray, and Pap smear in the routine follow-up program for cervical cancer patients previously treated with radiotherapy. Methods: The records of women who had developed recurrent cervical cancer after radiotherapy were retrospectively reviewed. The optimal procedure for the detection of recurrence was evaluated according to the disease-free interval (DFI). Survival analysis was performed based on the Kaplan-Meier method and comparisons between groups were made using the log-rank test. Results: A total of 146 recurrent cervical cancer patients were included in our database. The majority of recurrences were diagnosed either by symptoms, physical examination, or CT scan. The patients whose recurrent disease was detected by Pap smear, physical examination, or CT scan had a significantly longer survival than those detected by symptoms. When analyzed according to DFI, physical examination, and CT scan led to the detection of recurrence in patients with a DFI of 1-5 years. In contrast, chest X-ray and Pap smear only had a clinical impact on the diagnosis of recurrence in patients with a DFI of 1-2 years. Conclusions: Chest X-ray and Pap smear can be routinely performed for the first 2 years after radiotherapy, but can be omitted or used sparingly thereafter. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage IIB cervical cancer. Methods: We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups. Results: Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p=0.77), PFS (log-rank, p=0.57), and OS rates (log-rank, p=0.41) to definitive radiotherapy alone. The frequencies of acute grade 3–4 toxicities were similar between the two groups (24.2% versus 24.5%, p=1.0), whereas the frequencies of grade 3–4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p=0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3–4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97–5.99, p=0.059). Conclusions: Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of this study was to compare the efficacy of postoperative pelvic radiotherapy plus concurrent chemotherapy with that of extended-field irradiation (EFRT) in patients with FIGO Stage IA2–IIb cervical cancer with multiple pelvic lymph node metastases. Methods: We retrospectively reviewed the medical records of patients with FIGO Stage IA2–IIb cervical cancer who had undergone radical surgery between April 1997 and March 2008. Of these, 55 patients who demonstrated multiple pelvic lymph node metastases were treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy (n=29) or EFRT (n=26). Thirty-six patients with single pelvic node metastasis were also treated postoperatively with pelvic radiotherapy plus concurrent chemotherapy. The recurrence rate, progression free survival (PFS), and overall survival (OS) were compared between the treatment groups. Results: Pelvic radiotherapy plus concurrent chemotherapy was significantly superior to EFRT with regard to recurrence rate (37.9% vs 69.2%, p=0.0306), PFS (log-rank, p=0.0236), and OS (log-rank, p=0.0279). When the patients were treated with pelvic radiotherapy plus concurrent chemotherapy, there was no significant difference in PFS or OS between the patients with multiple lymph node metastases and those with single node metastases. With regards to grade 3–4 acute or late toxicities, no statistically significant difference was observed between the two treatment groups. Conclusions: Postoperative pelvic radiotherapy plus concurrent chemotherapy is superior to EFRT for treating patients with FIGO Stage IA2–IIb cervical cancer displaying multiple pelvic lymph node metastases. [ABSTRACT FROM AUTHOR]

Background: The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT).Methods: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005 to 2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched-cohort analysis were compared.Results: A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p = 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02-1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort.Conclusion: The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted. [ABSTRACT FROM AUTHOR]