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Preoperative Cancer Antigen 125 Level as Predictor for Complete Cytoreduction in Ovarian Cancer: A Prospective Cohort Study and Systematic Review.

ABSTRACT: The tumor marker 'cancer antigen 125' (CA-125) plays a role in the management of women with advanced stage ovarian cancer. This study aims to describe the predictive value of pre-treatment CA-125 level and the reduction after neoadjuvant chemotherapy (NACT) on surgical outcome. A systematic review and a prospective clinical study were performed. Multiple databases were searched from database inception to April 2022. The clinical study is part of a randomized controlled trial named "PlaComOv-study". A regression analysis was performed to demonstrate correlations between preoperative CA-125 levels, CA-125 reduction after NACT, and surgical outcome. Fourteen relevant articles were analyzed of which eleven reported that lower preoperative CA-125 levels were associated with a higher probability of complete cytoreduction. In the clinical study, 326 patients with FIGO stage IIIB-IV ovarian cancer who underwent CRS were enrolled from 2018 to 2020. Patients who underwent interval CRS with preoperative CA-125 levels ≤35 kU/L had higher odds of achieving complete CRS than patients with CA-125 level >35 kU/L (85% vs. 67%, OR 2.79, 95%CI 1.44-5.41, p = 0.002). In multivariable analysis with presence of ascites and peritoneal carcinomatosis, normalized preoperative CA-125 did not appear as a significant predictor for complete CRS. In literature, preoperative CA-125 levels ≤35 kU/L were associated with a significant higher percentage of complete CRS in univariable analysis. According to our cohort study, preoperative CA-125 level ≤35 kU/L cannot independently predict surgical outcome either for primary or interval CRS.

SUBMITTER: Brons PE

PROVIDER: S-EPMC9740757 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Preoperative Cancer Antigen 125 Level as Predictor for Complete Cytoreduction in Ovarian Cancer: A Prospective Cohort Study and Systematic Review.

Brons Puck E PE Nieuwenhuyzen-de Boer Gatske M GM Ramakers Christian C Willemsen Sten S Kengsakul Malika M van Beekhuizen Heleen J HJ

Cancers 20221122 23

Background: The tumor marker ‘cancer antigen 125’ (CA-125) plays a role in the management of women with advanced stage ovarian cancer. This study aims to describe the predictive value of pre-treatment CA-125 level and the reduction after neoadjuvant chemotherapy (NACT) on surgical outcome. Methods: A systematic review and a prospective clinical study were performed. Multiple databases were searched from database inception to April 2022. The clinical study is part of a randomized controlled trial ...[more]

PMID: 36497218

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Project description:UnlabelledBackgroundThere is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS).MethodsWe identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration.ResultsThe CA-125 level of 1.68?×?nadir was defined as the indicator of recurrent disease (p?<?0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31?days (ranging from 1 to 391?days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of?<?1.68?×?nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p?=?0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level???1.68?×?nadir at relapse (69.4 and 13.8?months) were longer than those with a CA-125 level?>?1.68?×?nadir at relapse (55.7 and 10.4?months; p?=?0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p?=?0.02 and 0.04 respectively).ConclusionsThe increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.

Project description:The cornerstone of ovarian cancer treatment is complete surgical cytoreduction. The gold-standard option in the absence of extra-abdominal metastases and intra-abdominal inoperable circumstances is primary cytoreductive surgery (CRS). However, achieving complete cytoreduction is challenging, and only possible in a selected patient population. Preoperative imaging modalities such as [18F]FDG PET/CT could be useful in patient selection for cytoreductive surgery. In our systematic review and meta-analysis, we aimed to evaluate the role of preoperative [18F]FDG PET/CT in predicting complete cytoreduction in primary and secondary debulking surgeries. Publications were pooled from two databases (PubMed, Mendeley) with predefined keywords "(ovarian cancer) AND (FDG OR PET) AND (cytoreductive surgery)". The quality of the included studies was assessed with the Prediction model Risk Of Bias Assessment Tool (PROBAST). During statistical analysis, MetaDiSc 1.4 software and the DerSimonian-Laird method (random effects models) were used. Primary and secondary cytoreductive surgeries were evaluated. Pooled sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated and statistically analyzed. Results were presented in forest plot diagrams and summary receiver operating characteristic (SROC) curves. Overall, eight publications were included in our meta-analysis. Four publications presented results of primary, three presented results of secondary cytoreductions, and two presented data related to both primary and secondary surgery. Pooled sensitivities, specificities, and positive and negative predictive values were the following: in the case of primary surgeries: 0.65 (95% CI 0.60-0.71), 0.73 (95% CI 0.66-0.80), 0.82 (95% CI 0.77-0.87), 0.52 (95% CI 0.46-0.59); and in the case of secondary surgeries: 0.91 (95% CI 0.84-0.95), 0.48 (95% CI 0.30-0.67), 0.88 (95% CI 0.81-0.93), 0.56 (95% CI 0.35-0.75), respectively. The PPVs of [18F]FDG PET/CT proved to be higher in cases of secondary debulking surgeries; therefore, it can be a valuable predictor of complete successful secondary cytoreduction.

Project description:ImportanceInternational guidelines use cancer antigen (CA) 125 thresholds to recommend which patients with pelvic masses should undergo evaluation by gynecologic oncologists for ovarian cancer. However, CA-125 thresholds were developed from White populations. If CA-125 levels differ among patient populations, current guidelines may contribute to delayed ovarian cancer diagnoses among women of other races and ethnicities than White.ObjectiveTo examine CA-125 levels at ovarian cancer diagnosis by patient race and ethnicity and associations of elevated CA-125 levels with timely treatment.Design, setting, and participantsThis retrospective cohort study included all patients with ovarian cancer diagnosed between January 1, 2004, and December 31, 2020, using the US National Cancer Database. The data analysis was performed between November 1, 2023, and July 10, 2024.ExposurePatient race and ethnicity as identified in the National Cancer Database.Main outcome and measuresCancer antigen 125 level was defined as elevated or borderline and negative or normal. Multivariable logistic regression models were used to examine the association of patient race and ethnicity with CA-125 level overall and for epithelial and high-grade serous cancers. Generalized linear models were used to examine the association of CA-125 level with days from diagnosis to chemotherapy start for patients with stage II to IV ovarian cancer.ResultsOf the 250 749 patients with ovarian cancer diagnosed between 2004 and 2020 (median [IQR] age, 62.0 [52.0-73.0] years; 0.4% American Indian, 3.7% Asian, 8.6% Black, 85.2% White, and 2.0% other or unknown race and 6.7% Hispanic, 88.8% non-Hispanic, and 4.6% of unknown ethnicity), 212 477 had measured CA-125 levels, and 88.2% had an elevated CA-125 level at diagnosis. Patients with American Indian, Asian, or Black race were less likely to have an elevated CA-125 level at ovarian cancer diagnosis than White patients. In multivariable analyses adjusted for stage, comorbidities, and menopausal status, Black patients had lower odds of elevated CA-125 levels (adjusted odds ratio [AOR], 0.77; 95% CI, 0.74-0.81) compared with White patients, as did American Indian patients (AOR, 0.77; 95% CI, 0.62-0.94). Among patients with high-grade serous ovarian cancer only, Black patients had a lower odds of having an elevated CA-125 level at diagnosis (AOR, 0.81; 95% CI, 0.73-0.91). Patients with stage II to IV ovarian cancer with false-negative CA-125 findings at diagnosis had 9.38 days longer (95% CI, 8.43-10.34 days) to chemotherapy start compared with patients with an elevated CA-125 level.Conclusions and relevanceIn this cohort study of patients with ovarian cancer, American Indian and Black patients were 23% less likely to have an elevated CA-125 level at diagnosis. Current CA-125 thresholds may miss racially and ethnically diverse patients with ovarian cancer. Work is needed to develop inclusive CA-125 thresholds and diagnostic guidelines and not compound disparities in ovarian cancer diagnosis and treatment.

Project description:Background:To assess the ability of preoperative positron emission tomography/computed tomography (PET/CT) scans to predict postoperative residual disease in advanced epithelial ovarian cancer (AEOC). Methods:Thirty-one women with suspected AEOC were enrolled in our prospective study before surgery from July 2016 to December 2017. Complete resection was determined as no residual disease (R0) after surgery. A PET/CT scan was obtained within 2 weeks before surgery in our hospital. The PET score was the sum of each score of the radiological criteria from Suidan's model. The correlations between the PET score and tumor burden and surgical complexity were evaluated by Pearson correlation analysis. T-test or Fisher's exact test was used to compare differences in the variables between the complete and incomplete resection groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the PET score for predicting complete postoperative resection. Results:The median [range] of PET score was 2 [0-8], and the PET score in 20 (65%) patients was less than 3. Complete resection was achieved in 11 (35.5%) patients after surgery, including 10 (90.91%) with low PET scores and only 1 (9.09%) with a high score. The PET score had a significant positive correlation with tumor burden [Eisenkop: r=0.603, P<0.001; peritoneal cancer index (PCI): r=0.522, P=0.003] but not with surgery complexity (Aletti: r=0.291, P=0.113). Patients with lower PET scores (P=0.046) and tumor burdens (Eisenkop: P=0.013; PCI: P=0.012) had higher rates of complete resection. The PET score and tumor burden were effective for predicting complete resection. The AUCPET, AUCEisenkop, and AUCPCI were 0.797 (95% CI: 0.633-0.961, P=0.01), 0.847 (95% CI: 0.707-0.988, P=0.003), and 0.811 (95% CI: 0.653-0.969, P=0.007), respectively. However, surgery complexity was not useful for assessing complete resection. Conclusions:The preoperative PET score can noninvasively reflect tumor burden and helps predict complete resection after surgery in AEOC patients.

Project description:BackgroundSecondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation.MethodsWe randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival.ResultsA total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.ConclusionsIn this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).

Dataset Information

Preoperative Cancer Antigen 125 Level as Predictor for Complete Cytoreduction in Ovarian Cancer: A Prospective Cohort Study and Systematic Review.

Publications

Preoperative Cancer Antigen 125 Level as Predictor for Complete Cytoreduction in Ovarian Cancer: A Prospective Cohort Study and Systematic Review.

Similar Datasets

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