Neoadjuvant Chemotherapy Followed By Interval Debulking Surgery Research Articles

Leave it in the past - primary treatment modality for high-grade epithelial ovarian cancer is not associated with secondary cytoreduction outcomes: A Memorial Sloan Kettering Cancer Center Team Ovary study

ObjectivesTo compare outcomes of patients with high-grade epithelial ovarian cancer (EOC) who underwent secondary cytoreduction surgery (SCS) after up-front treatment with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) versus primary debulking surgery (PDS). MethodsPatients with high-grade EOC who underwent SCS from 2/1/2004–10/31/2021 were classified by up-front treatment. Clinical and treatment characteristics were compared between cohorts. Progression-free survival (PFS2) and overall survival (OS2) following SCS were compared using a Cox model adjusted for stage, age at SCS, and number of years between end of chemotherapy and SCS. ResultsOf 374 patients, 62 (17%) underwent NACT-IDS and 312 (83%) PDS. Justification for NACT was disease extent (n = 57, 92%), comorbidities (n = 3, 5%), and thromboembolism (n = 2, 3%). The NACT-IDS cohort had a higher median age at SCS (64 years [IQR: 56–70] vs 59 years [IQR: 53–66]; P = .03), higher proportion of stage III/IV disease (100% vs 81%; P < .001), and shorter median interval between end of chemotherapy and SCS (1.5 years [IQR: 1.1–2.3] vs 1.9 years [IQR: 1.3–3.1]; P = .01). Achievement of complete gross resection at SCS did not differ between NACT-IDS and PDS (84% vs 88%; P = .18). PFS2 (HR: 1.19, 95% CI: 0.83–1.71) and OS2 (HR: 0.96, 95% CI: 0.57–1.63) did not vary by primary treatment modality after adjusting for clinically relevant covariates. ConclusionsDespite more extensive disease at presentation, patients with high-grade EOC who recur after NACT-IDS seem to have similar surgical and survival outcomes after SCS compared to patients who recur after PDS, suggesting that prior NACT-IDS should not preclude SCS.

Clinical implications of neoadjuvant chemotherapy in advanced endometrial cancer: a multi-center retrospective cohort study

BackgroundThe mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer.MethodsFrom the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC–IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients’ clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed.ResultsOverall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032).ConclusionsNAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

Effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer

Objectives: To investigate the effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer. Methods: A retrospective study was performed among 210 patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy from May 1, 2007 to December 1, 2015. 121 patients with NACT-IDS (Neoadjuvant chemotherapy followed by interval debulking surgery) were enrolled. The patients were divided into observation group (NACT-IDS + IP group, n = 28) and control group (NACT-IDS + IV group, n = 93) depending on whether intraperitoneal chemotherapy was used after interval debulking surgery. The effects of intraperitoneal chemotherapy after NACT-IDS on PFS (progression-free survival) and OS (overall survival) were analyzed and the influencing factors were explored through multivariate analysis. The competitive model was used to analyze the effect of intraperitoneal chemotherapy after NACT-IDS on tumor recurrence. Toxicities associated with adjuvant chemotherapy were also analyzed between two groups. The effect of neoadjuvant chemotherapy cycles on prognosis and the correlation between postoperative CA125 decline and recurrence were evaluated. Results: Intraperitonal chemotherapy and R0 (no gross residual) were independent factors for PFS, with HRs of 0.560 (95% CI, 0.342–0.918, p = 0.022) and 0.578 (95% CI, 0.377–0.887, p = 0.012). There was no independent factor associated with OS. Significant difference in PFS was detected among the R0 + IP group, R0 + IV group, non-R0 + IP group and non-R0 + IV group. In patients with R0 tumor reduction, IP patients showed significantly better PFS, bonferronei adjusted p = 0.036. In patients without R0 tumor reduction, no significant difference was detected between IP and IV group, bonferronei adjusted p = 0.28. There were no significant differences of grade 3–4 toxicities, abdominal pain, treatment delays, dose reductions, and treatment modifications in NACT-IDS + IP group and NACT-IDS + IV group. Neoadjuvant chemotherapy cycles (≤3 and &gt;3) were not the influencing factors of PFS or OS and did not affect platinum-sensitive relapse or platinum-resistant relapse. The decrease in postoperative CA125 was not related to platinum-sensitive recurrence or platinum-resistant recurrence. Conclusions: Neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval debulking surgery could improve the PFS of patients with advanced epithelial ovarian cancer compared to intravenous chemotherapy without significant differences in toxicity.

Factors predicting postoperative morbidity after cytoreductive surgery for ovarian cancer: a systematic review and meta-analysis.

ObjectiveAdvances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable.MethodsElectronic databases were searched. Meta-analysis was conducted using random-effects models.ResultsFifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001).ConclusionOur study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS.Trial RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42021282770

Perioperative outcomes and survival in elderly women with ovarian cancer

Objectives: The rate of perioperative adverse events, postoperative outcomes and survival between patients aged 60-69 yo versus those ≥70 yo undergoing surgery for the primary treatment of advanced ovarian cancer (OC). Methods: We retrospectively identified all patients ≥60 years old treated surgically for primary advanced high-grade OC at our institution between January 2016 and December 2018. Institutional National Surgical Quality Improvement Program data were obtained for post-operative complications. Additional data were abstracted from medical records. Results are stratified based on the treatment approach: primary debulking surgery (PDS) or neo-adjuvant chemotherapy followed by interval debulking surgery (NACT/IDS). Appropriate statistical tests were performed. Results: A total of 77 patients were analyzed; 45 were between 60-69 years and 32 were ≥70 years. There were no differences in preoperative BMI, ECOG, ASA, CCI, polypharmacy, baseline bloodwork and stage (Table 1). Only 2 patients ≥70 years (0.6%) saw a geriatric oncology specialist prior to treatment. A total of 32 patients underwent PDS (60-69yo: n=18, ≥70yo: n=14), and 45 patients had NACT/IDS (60-69yo: n=27, ≥70yo: n=18). In both PDS and NACT/IDS groups, there were no differences in the post-operative adverse events between the two age groups. Older patients in the NACT/IDS group received less total platinum and taxane chemotherapy before and after surgery compared to NACT/IDS patients aged 60-69 years (p Download : Download high-res image (144KB) Download : Download full-size image Download : Download high-res image (263KB) Download : Download full-size image Conclusions: Although baseline characteristics were comparable between younger and older OC patients, reasons for PDS versus NACT/IDS were difficult to extrapolate from the medical record. Age was not a factor influencing perioperative outcomes of advanced ovarian cancer patients and the main predictor of outcomes was treatment approach. Since PDS is the main predictor of survival, a standardized, multi-disciplinary approach to optimize the management of older patients with ovarian cancer is necessary. Use of a formal assessment tool and consultation with a geriatric specialist may facilitate more patients undergoing PDS.

Nadir CA-125 serum levels during neoadjuvant chemotherapy and no residual tumor at interval debulking surgery predict prognosis in advanced stage ovarian cancer

BackgroundRecent phase III randomized trials have suggested that neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) is a treatment option for patients with advanced epithelial ovarian cancer. This study aimed to use CA-125 and computed tomography (CT) scanning to generate a simple and clinically applicable model of predicting complete cytoreduction by interval debulking surgery (IDS) and the overall survival in patients who receive taxane/platinum-based chemotherapy as neoadjuvant chemotherapy (NACT).MethodsPatients with stage IIIc or IV epithelial ovarian cancer who underwent taxane/platinum-based NACT followed by IDS in Gunma Prefectural Cancer Center, Takasaki General Medical Center, and Gunma University from April 2009 to March 2015 were included. Patients underwent a CT scan to confirm confirm tumors unresectable by standard surgery before NACT. CA-125 levels were measured pre-NACT, after each cycle of NACT, and before IDS. CT was also performed before IDS to evaluate tumor metastasis. Data were collected retrospectively and analyzed to determine the predictive factors of complete resection and overall survival.ResultsAmong 63 patients who received NACT-IDS, 43 and 20 patients had stages IIIc and IV epithelial ovarian cancer at diagnosis, respectively. CT predictors of residual tumors after IDS such as extra-ovarian implants (P = 0.009) and omental cakes (P = 0.038) were not present. Univariate analysis revealed that the independent factors for overall survival were no residual tumor by IDS (P = 0.0016) and CA125 ≤ 20 U/ml before IDS (P = 0.0011).ConclusionsAlthough this study had a small sample size, NACT-IDS used to completely remove macroscopic disease which significantly improved the prognosis of patients with preoperative CA-125 ≤ 20 U/ml. Results from this study provide useful information for future studies on the management of patients with advanced epithelial ovarian cancer.

Study of upfront surgery versus neoadjuvant chemotherapy followed by interval debulking surgery for patients with stage IIIC and IV ovarian cancer, SGOG SUNNY (SOC-2) trial concept.

BackgroundTwo randomized phase III trials (EORTC55971 and CHORUS) showed similar progression-free and overall survival in primary or interval debulking surgery in ovarian cancer, however both studies had limitations with lower rate of complete resection and lack of surgical qualifications for participating centers. There is no consensus on whether neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) could be a preferred approach in the management of advanced epithelial ovarian cancer (EOC) in the clinical practice.MethodsThe Asian SUNNY study is an open-label, multicenter, randomized controlled, phase III trial to compare the effect of primary debulking surgery (PDS) to NACT-IDS in stages IIIC and IV EOC, fallopian tube cancer (FTC) or primary peritoneal carcinoma (PPC). The hypothesis is that PDS enhances the survivorship when compared with NACT-IDS in advanced ovarian cancer. The primary objective is to clarify the role of PDS and NACT-IDS in the treatment of advanced ovarian cancer. Surgical quality assures include at least 50% of no gross residual (NGR) in PDS group in all centers and participating centers should be national cancer centers or designed ovarian cancer section or those with the experience participating surgical trials of ovarian cancer. Any participating center should be monitored evaluating the proportions of NGR by a training set. The aim of the surgery in both arms is maximal cytoreduction. Tumor burden of the disease is evaluated by diagnostic laparoscopy or positron emission tomography/computed tomography scan. Patients assigned to PDS group will undergo upfront maximal cytoreductive surgery within 3 weeks after biopsy, followed by 6 cycles of standard adjuvant chemotherapy. Patients assigned to NACT group will undergo 3 cycles of NACT-IDS, and subsequently 3 cycles of adjuvant chemotherapy. The maximal time interval between IDS and the initiation of adjuvant chemotherapy is 8 weeks. Major inclusion criteria are pathologic confirmed stage IIIC and IV EOC, FTC or PPC; ECOG performance status of 0 to 2; ASA score of 1 to 2. Major exclusion criteria are non-epithelial tumors as well as borderline tumors; low-grade carcinoma; mucinous ovarian cancer. The sample size is 456 subjects. Primary endpoint is overall survival.Trial RegistrationClinicalTrials.gov Identifier: NCT02859038

Using an evidence-based triage algorithm to reduce 90-day mortality after primary debulking surgery for advanced epithelial ovarian cancer

ObjectiveTo evaluate the impact of an evidence-based triage algorithm to decide between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT/IDS) for advanced epithelial ovarian cancer (EOC). MethodsSurgical morbidity and mortality (M/M) after PDS for stage IIIC-IV EOC at Mayo Clinic after implementation of the triage algorithm (contemporary cohort, 2012-July 2016) were compared to that of a historic PDS cohort (2003−2011). ResultsMean age of the 232 women who met inclusion criteria in the contemporary cohort was 63.9 years. We observed a 71% decrease in 90-day mortality from 8.9% to 2.6% (P = 0.002) between the contemporary and historic cohorts. Accordion grade 3+ postoperative complications within 30 days after surgery decreased from 22.3% to 18.3% (P = 0.19). Among those with a grade 3+ complication, 90-day mortality rates decreased from 28.3% in the historic cohort to 2.4% in the contemporary cohort (P < 0.001) suggesting patients were better able to tolerate complex surgery. When compared to the historic PDS cohort, oncologic outcomes were also improved in the contemporary PDS cohort. Complete as well as optimal (residual disease ≤1 cm) cytoreduction rates increased (45.5% vs. 62.5% and 84.5% vs. 95.3%, respectively, P < 0.001), and the proportion of women starting chemotherapy within 42 days of surgery increased (57.4% vs. 69.8%, P = 0.001). Three-year overall survival was 53% in the historic cohort and 66% in the contemporary cohort (P < 0.001). ConclusionsUse of the Mayo triage algorithm for EOC was associated with reduced 90-day mortality after PDS and improved oncologic outcomes. Surgical risk assessment is a critical aspect of treatment planning in the primary management of EOC and should be incorporated into practice.

A study of clinicopathologic factors as indicators for early prediction of suboptimal debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer.

This study aimed to evaluate early clinicopathologic factors predicting gross residual disease after neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. We analyzed clinicopathologic data of 68 patients with ovarian cancer who were treated with neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) between March 2006 and December 2016. All the patients received three cycles of NAC followed IDS. We evaluated all possible clinicopathologic characteristics, including reduction rates of serum CA-125 after each NAC and seven initial abdominopelvic computed tomography (CT) findings related to disease severity. After IDS, no gross residual disease was found in 46 (67.6%) patients and 22 (33.4%) patients had gross residual disease. Multivariate analysis identified that reduction rate of CA-125 after 2nd NAC, body mass index (BMI) and small bowel lesion in the initial CT findings were significantly associated with gross residual disease after IDS (P = 0.005, 0.030, 0.001, respectively). The optimal cutoff value predicting gross residual disease were less than 50% of CA-125 reduction rate after 2nd NAC and low BMI (<23 kg/m2 ). The combined receiver operating characteristic curve analysis of these factors showed good performance for predicting gross residual disease after IDS (area under the curve = 0.845). A model using small bowel mesentery involvement on CT, BMI (<23 kg/m2 ) and less than 50% reduction of the initial CA-125 level after the 2nd NAC is highly predictive of gross residual disease after IDS in advanced ovarian cancer patients. These results may be helpful in further treatment planning and patients counseling.

Neoadjuvant chemotherapy or primary debulking surgery in FIGO IIIC and IV patients; results from a survey study in the Netherlands

IntroductionPrimary debulking surgery (PDS) followed by adjuvant chemotherapy is historically recommended as first line treatment for advanced stage ovarian cancer. Two randomized controlled trials, however, showed similar efficacy and reduced toxicity with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Nevertheless, uptake of NACT-IDS varies widely between hospitals, which cannot be explained by difference in patient populations. In this survey, we therefore aimed to evaluate the views on NACT-IDS among all Dutch gynaecologists and medical oncologists involved in the treatment of ovarian cancer. Study designAn e-mail link to the online questionnaire was sent to all medical oncologists and gynaecologists in the Netherlands, regardless of their (sub)specializations. The data was analysed using descriptive statistics and chi-square tests were used to analyse differences between groups. ResultsThree-hundred-forty physicians were invited to fill out the questionnaire. After two reminders, 167 of them responded (49%). Among the responders, 82% of the gynaecologists versus 93% of the medical oncologists considered the available evidence sufficiently convincing to treat advanced stage ovarian cancer patients with NACT-IDS (p = 0.076). Moreover, 33% of gynaecologists and 62% of medical oncologists preferred NACT-IDS to PDS as first line treatment (p = 0.001). While most responders (86%) indicated that selecting the right patients for NACT-IDS is difficult, those with bulky disease, FIGO stage IV or metastases near the porta hepatica were most likely to undergo NACT-IDS. ConclusionThe majority of Dutch gynaecologists and medical oncologists adopted NACT-IDS as an alternative treatment approach for advanced stage primary ovarian cancer. About two-thirds of medical oncologists and one-third of gynaecologists prefer NACT-IDS to PDS as first line treatment in this setting. Improving patient selection is considered of paramount importance.

Primary Cytoreductive surgery (PS) and Neoadjuvant Chemotherapy (NACT) followed by Interval Debulking Surgery (NACT/IDS) in Advanced Epithelial Ovarian Cancer (EOC): Regional Cancer Centre Experience

Primary Cytoreductive surgery (PS) and Neoadjuvant Chemotherapy (NACT) followed by Interval Debulking Surgery (NACT/IDS) in Advanced Epithelial Ovarian Cancer (EOC): Regional Cancer Centre Experience

Feasibility of Upfront Debulking Surgery versus Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery for Advanced Ovarian Cancer

Background: Inappropriately ovarian cancer cannot be detected until an advanced stage. Radical debulking surgery is considered the cornerstone in the management of advanced ovarian cancer pointing to complete tumor resolution. Unless optimal debulking cannot be achieved, these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT) has been recommended as a novel therapeutic modality to a diversity of malignant tumors when the disease is not willing to optimal surgical resection at the time of diagnosis or the patient who unfit for aggressive debulking surgery. The purpose of this study is to compare survival in the patient with advanced ovarian cancer (stage III/IV) underwent primary debulking surgery followed by adjuvant chemotherapy (PDS-ACTR) to those who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Results: Neoadjuvant chemotherapy (NACT-IDS) showed significant complete cytoreduction and decreased in surgical morbidity in comparison to primary debulking surgery (PDS-ACTR). NACT-IDS showed significant improvement in progression-free survival (P-value 0.002) and overall survival (P-value 0.03) in comparison to PDS-ACTR. Response to NACT and residual volume were the two independent prognostic factors for overall survival. Conclusion: NACT-IDS for advanced ovarian cancer (III/IV) resulted in higher frequency of complete resection with no residual tumor, less post-operative surgical morbidity and significant increase progression-free survival and overall survival. Both responses to NACT and residual tumor volume were the two independent prognostic factors for survival in ovarian cancer.

The role of neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer: a systematic review and meta-analysis of randomized controlled trials and observational studies.

ObjectiveWe aimed to performed a meta-analysis and systematic review on the role of neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) in advanced ovarian cancer (AOC) patients.Materials and MethodsWe searched PubMed, EMBASE, and the Cochrane Library for relevant articles. All statistical analyses were performed in Review Manager 5.3.5.ResultsIn two randomized controlled trials (RCTs), there was no significant difference in overall survival (OS) (HR = 0.93, 95% CI: 0.81–1.06) or progression-free survival (PFS) (HR = 0.97, 95% CI: 0.86–1.09). Few adverse events (HR = 0.37, 95% CI: 0.19–0.72) and a high optimal debulking surgery rate (HR = 1.69, 95% CI: 1.50–1.91) were observed with NACT. In 22 observational studies, primary debulking surgery (PDS) yielded better OS (HR = 1.38, 95% CI: 1.19–1.60) but not progression-free survival (PFS) (HR = 1.03, 95% CI: 0.86–1.23). An increased optimal cytoreduction rate (HR = 1.17, 95% CI: 1.12–1.22) was observed with NACT. Irrespective of the degree of residual disease, OS was longer in the PDS group than that in the NACT group. Patients with FIGO stage III (HR = 1.43, 95% CI: 1.05–1.95) and IV (HR = 1.14, 95% CI: 1.06–1.23) disease had better survival with PDS.ConclusionsTreatment with NACT-IDS improves perioperative outcomes and optimal cytoreduction rates, but it may not improve OS. NACT-IDS is not inferior to PDS-CT in terms of survival outcomes in selected AOC patients. Future studies should focus on candidate selection for NACT.

Serum CA 125 Level after Neoadjuvant Chemotherapy is Predictive of Prognosis and Debulking Surgery Outcomes in Advanced Epithelial Ovarian Cancer.

Recently, neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) has been recommended for selected patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV disease and bulky tumors. The aim of this study was to evaluate associations between post-NACT serum CA 125 levels, surgical outcomes, and clinical outcomes in patients with advanced epithelial ovarian cancer. We retrospectively analyzed 107 patients with FIGO stage III or IV ovarian cancer who were treated with NACT-IDS at the Gynecology Department of Kanagawa Cancer Center between January 2001 and December 2012. Serum CA 125 levels after NACT were significantly lower in the complete/optimal IDS group compared to the suboptimal IDS group (mean±standard deviation: 48.1±27.6 vs. 346.5±295.2 U/mL, p<0.01). Patients with low preoperative CA 125 levels (<35 U/mL) had a higher probability of optimal IDS (78.1±41.9% vs. 33.3±19.2%, p<0.01) and longer progression-free survival (mean±standard deviation: 30.4±14.3 months vs. 21.3±7.3 months, p<0.05) than patients with high CA 125 levels (>100 U/mL). Patients with low CA 125 levels (<35 U/mL) had a higher probability of complete/optimal IDS and longer progression-free survival compared to patients with high CA 125 levels (>100 U/mL).

Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome

ObjectiveTo establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL). Material and methodsThis is a single-Institution, superiority, randomised phase III trial enrolling supposed AEOC women. Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index (PI) of tumour load. All AEOC women with PI≥8 or≤12 (considered as HTL) were included. They were randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy (arm A, standard), or NACT followed by IDS (NACT/IDS) (arm B, experimental). Co-primary outcome measures were postoperative complications (graded according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system) and progression free survival (PFS); secondary outcomes were overall survival, and quality of life (QoL). QoL was assessed using the EORTC QoL questionnaires. A sample size of 110 patients was required for the analysis of the first co-primary end-point (major peri-operative morbidity) whereas recruitment is still on-going to achieve the statistical power on PFS. ResultsBetween October 2011 and November 2014, we registered 280 AEOC. Of the 110 eligible women, 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery, rates of complete residual disease (residual tumour=0 cm) were superimposable between the groups (45.5% versus 57.7%; p=0.206). Twenty-nine patients (52.7%) in arm A experienced early grade III–IV complications versus three patients (5.7%) in IDS (p=0.0001). The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage (17/55 women (30.9%) in arm A versus 1/52 (1.9%) in arm B, p=0.0001). Three grade IV (5.4%) (i.e., two re-operations for postoperative haemorrhage and one septic multi-organ failure), and two grade V (3.6%) (two deaths for acute cardiopulmonary failure) early complications were observed in arm A only.Mean QoL scores of several scales/items were shown to ameliorate over time in both arms. Emotional functioning, cognitive functioning, nausea/vomiting, dyspnoea, insomnia and hair loss were statistically and clinically better in NACT/IDS compared to PDS arm. ConclusionsPerioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS arm than PDS in AEOC patients with very HTL. Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL.

Reduction of CA125 Levels During Neoadjuvant Chemotherapy Can Predict Cytoreduction to No Visible Residual Disease in Patients with Advanced Epithelial Ovarian Cancer, Primary Carcinoma of Fallopian tube and Peritoneal Carcinoma.

Background and aims. To determine whether reduction of CA125 levels is a predictive factor for cytoreduction to no visible residual disease (NVRD) and chemotherapeutic sensitivity in advanced epithelial ovarian carcinoma (EOC), primary carcinoma of fallopian tube and peritoneal carcinoma patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS).Methods. This was a single-team-based study of advanced EOC, primary carcinoma of fallopian tube and peritoneal carcinoma patients diagnosed between 1996 and 2015 at Peking Union Medical College Hospital. Patients were treated with NAC-IDS by one gynecologic oncologist. Demographic data, CA125 levels, radiographic data, and chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with optimal cytoreduction to NVRD and chemotherapy-sensitivity.Results. One hundred and eighteen patients met the study inclusion criteria. Thirty-seven (31.4%) patients underwent resection to NVRD. The median serum CA125 level at presentation and before IDS was 1814.5 U/ml and 205.9 U/ml, respectively. In the univariate analysis, histology, a preoperative CA125 of ≤200 U/ml and a >80% reduction of CA125 between presentation and IDS were significantly associated with the likelihood of NVRD (P=0.014, 0.000, 0.000, respectively). Multivariate analysis revealed that, of the various CA125 parameters tested, preoperative CA125 ≤200 U/ml was the only independent predictor of NVRD (odds ratio 3.667, 95% confidence interval 1.337-10.057; P=0.012). Preoperative CA125 ≤200 U/ml was also significantly associated with chemotherapy-sensitive disease in the univariate analysis (P=0.037).Conclusions. EOC patients who received NAC-IDS and had a preoperative CA125 level of ≤200 U/ml were highly likely to be cytoreduced to NVRD and to exhibit chemotherapeutic sensitivity.

Primary surgery or interval debulking for advanced epithelial ovarian cancer: does it matter?

The aim of the present study was to investigate the surgical complexity, the postoperative morbidity, and the survival of the women after primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for advanced epithelial ovarian cancer. We consecutively included all patients who underwent debulking surgery at our institution between January 2007 and December 2012 for stages IIIc and IV of epithelial ovarian cancer. Of the 332 patients included, 165 (49.7%) underwent PDS, and 167 (50.3%) had NACT-IDS. Complete intraperitoneal cytoreduction was achieved in 70.9% after PDS and in 59.9 % after NACT-IDS. Residual disease of greater than 1 cm was left in 18.5% and 27.5% after PDS and NACT-IDS, respectively. Compared with NACT-IDS, PDS was associated with higher surgical complexity (P < 0.001), longer operating time (P < 0.001), greater blood loss (P < 0.001), longer hospitalization (P = 0.001), and a higher rate of major postoperative complications (26.7% vs 16.8%). No statistical difference in the median overall survival (OS) was found between the patients having complete cytoreduction and residual disease of 1 cm or less after NACT-IDS. Furthermore, no statistical difference in the median OS was found between the patients with macroscopic residual disease (≤1 vs >1 cm) after NACT-IDS. Patients with residual disease of greater than 1 cm after PDS had a median OS of 15 months. We suggest that NACT-IDS may be a better treatment alternative for the group of highly selected women not suitable for PDS, where expected suboptimal cytoreduction does not have any appreciable survival benefit and exposes them for unnecessary risks. A substantial number of women who receive either PDS or NACT-IDS have greater than 1 cm of tumor tissue left after the operation. These women probably have no survival benefit from the operation, and future studies should focus on how to select these women preoperatively.

Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

To compare the survival and perioperative morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with advanced epithelial ovarian cancer (EOC). We retrospectively reviewed 67 patients with stage IIIC or IV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009. Wherein, 37 and 30 patients underwent PDS and NAC/ IDS, respectively. No difference in overall survival (OS) or progression-free survival (PFS) was observed between NAC/IDS group and PDS group (OS: 41.2 vs. 39.1 months, P=0.23; PFS: 27.1 vs. 24.3 months, P=0.37). The optimal debulking rate was 60% in the NAC/IDS group, which was significantly higher than that in the PDS group (32.4%) (P=0.024). The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion, lower nasogastric intubation rate, and earlier ambulation and recovery of intestinal function than the PDS group (P<0.05). NAC/IDS is less invasive than PDS, and offers the advantages regarding optimal cytoreduction rate, intraoperative blood loss, and postoperative recovery, without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC. Therefore, NAC/IDS may be a valuable treatment alternative for EOC patients.

Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer.

To compare the survival and perioperative morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with advanced epithelial ovarian cancer (EOC). We retrospectively reviewed 67 patients with stage IIIC or IV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009. Wherein, 37 and 30 patients underwent PDS and NAC/IDS, respectively. No difference in overall survival (OS) or progression-free survival (PFS) was observed between NAC/IDS group and PDS group (OS: 41.2 vs. 39.1 months, P=0.23; PFS: 27.1 vs. 24.3 months, P=0.37). The optimal debulking rate was 60% in the NAC/IDS group, which was significantly higher than that in the PDS group (32.4%) (P=0.024). The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion, lower nasogastric intubation rate, and earlier ambulation and recovery of intestinal function than the PDS group (P<0.05). NAC/IDS is less invasive than PDS, and offers the advantages regarding optimal cytoreduction rate, intraoperative blood loss, and postoperative recovery, without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC. Therefore, NAC/IDS may be a valuable treatment alternative for EOC patients.

Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

ObjectiveTo evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC). MethodsUsing the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical–pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon–Mann–Whitney test. ResultsOne hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749U/mL and 161U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566U/mL v. 2077U/mL, p=0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233U/mL (p=0.001). In the NRD group, 38 patients (80%) had preoperative CA-125≤100U/mL compared to 33 patients (63.4%) in the OMD group (p=0.04). ConclusionsPatients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤100U/mL were highly likely to be cytoreduced to no residual disease.