Tertiary Cytoreductive Surgery Research Articles

Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors

BackgroundFew studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared to systemic therapy alone following the first recurrence and subsequent disease progressions. ObjectiveTo determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary. Study DesignThis is a multicenter, retrospective cohort study evaluating patients with recurrent adult granulosa cell tumor of the ovary enrolled in the MD Anderson Rare Gynecologic Malignancy Registry from 1970 to 2022. Study inclusion criteria consisted of histology-proven recurrent disease, at least one documented recurrence, and treatment/treatment planning at MD Anderson Cancer Center or Lyndon B. Johnson General Hospital. The primary exposure was cytoreductive surgery and the outcomes of interest were progression-free survival and overall survival. Survival analyses were restricted to eligible patients with resectable disease without medical barriers to surgery at each progression episode. Demographic and Clinicopathologic characteristics were summarized using descriptive statistics. Progression-free survival (after first, second, and third progression) and overall survival were estimated with methods of Kaplan and Meier and were modeled via cox proportional hazards regression. Multivariable analyses were performed for progression-free survival after first progression and overall survival. ResultsAmong the 369 patients with adult granulosa cell tumors of the ovary in the registry, there were 149 patients who met the study inclusion criteria. Secondary cytoreductive surgery was associated with a significant improvement in progression-free survival on univariable (HR 0.37, 95% CI 0.17 – 0.81, p = 0.01) and multivariable analyses (HR 0.42, 95% CI 0.19 – 0.92, p = 0.03). Those who underwent secondary cytoreductive surgery had a significantly improved median overall survival compared to those who did not undergo cytoreductive surgery (181.92 months vs 61.56 months, respectively; p = 0.002). Overall survival benefit remained statistically significant on multivariable analysis (HR 0.28, 95% CI 0.11 – 0.67, p = 0.004). Tertiary cytoreductive surgery was similarly associated with a significant improvement in progression-free survival (HR 0.43, 95% CI 0.26 – 0.70, p = 0.001). Despite a similar trend, quaternary cytoreductive surgery was not associated with a significant improvement in progression-free survival (HR 0.74, 95% CI 0.42 – 1.26, p = 0.27). ConclusionsAmong those with resectable disease and no medical contraindications to surgery, cytoreductive surgery may offer a beneficial impact on progression-free survival and overall survival in patients with recurrent adult granulosa cell tumor of the ovary.

Analysis of prognosis and associated factors in multiple recurrent epithelial ovarian cancer with three times or more cytoreductive surgeries

Objective: To explore the prognosis of epithelial ovarian cancer patients with multiple recurrences (≥2 times) who underwent three times or more cytoreductive surgeries, and to analyze the factors associated with prognosis. Methods: The clinicopathological data and follow-up data of 23 patients with ovarian cancer admitted to the Obstetrics and Gynecology Hospital of Fudan University from January 1, 2015 to January 30, 2022 with three times or more cytoreductive surgeries were collected. The degree of surgical resection, site of recurrence and metastasis, postoperative complications, and prognosis were retrospectively analyzed. The univariate Cox proportional hazards model was performed to identify the variables associated with survival. Results: (1) The median age of 23 patients with multiple recurrent ovarian cancer was 48 years old (44-55 years). Among them, 18 cases underwent tertiary cytoreductive surgery (TCS), 2 cases underwent quaternary cytoreductive surgery, 2 cases underwent quinary cytoreductive surgery, and 1 case underwent senary cytoreductive surgery. Among the 23 patients with multiple recurrent ovarian cancer, 21 cases (91%, 21/23) had serous carcinoma, 16 cases (70%, 16/23) had advanced stage (stage Ⅲ-Ⅳ), and 19 cases (83%, 19/23) had high differentiation. (2) Based on the premise that satisfactory cytoreduction was achieved by primary debulking surgery (PDS) and no visible residual disease (R0) was achieved by secondary cytoreductive surgery (SCS), the maximum diameter of the recurrent tumors was up to 10.0 cm and 62% (20/32) of patients with multiple metastatic sites. The R0 rate for three times or more cytoreductive surgeries (32 times in total) reached 88% (28/32), with a postoperative complication rate of 47% (15/32), and only 3% (1/32) for grade Ⅲ or above. During a median follow-up time of 31.1 months (20.6-43.9 months) after TCS, 20 patients (87%, 20/23) recurred after TCS, and 8 patients (35%, 8/23) eventually died of ovarian cancer. Among them, the three-year postoperative survival rate of 22 patients with R0 was 57.6%, and the patient with residual lesions ≥1 cm died at 9.2 months after TCS. (3) In univariate analysis, ages, the time interval between PDS and SCS >32 months, the interval between SCS and TCS >16 months, and no metastatic peritoneal carcinoma were associated with longer progression free survival after TCS (all P<0.05); while treatment-free interval (TFI) >10 months after SCS, the interval between SCS and TCS >16 months, no ascites and platinum-sensitive status were associated with disease-specific survival after TCS (all P<0.05). Conclusions: It is feasible to perform three times or more cytoreductive surgeries in patients with multiple recurrent ovarian cancer who are expected to achieve R0 and have manageable complications. However, the pros and cons of surgery need to be carefully evaluated for the patients whose ascites are massive and whose previous cytoreduction does not achieve R0. A prolonged TFI and previously longer surgical interval might get potential survival benefits.

A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE)

BackgroundMultimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian...

Treatment patterns and survival outcomes of recurrent adult-type granulosa cell tumors

Objectives: Granulosa cell tumors are characterized by indolent growth and late recurrence; treatment of recurrent disease is not standardized. We sought to evaluate the outcomes of patients who underwent secondary and tertiary cytoreductive surgery as part of treatment for recurrent granulosa cell tumor. Methods: A retrospective review was conducted of women diagnosed with primary or recurrent granulosa cell tumors at an urban university system between 2010 and 2019. Data collected included demographic, clinicopathologic, and treatment factors. Endpoints of treatment outcome was progression free survival. Statistical analyses were preformed using the Kaplan-Meier method, the log-rank test, and Fisher's exact test. Results: 75 patients diagnosed with primary or recurrent granulosa cell tumor were identified. After excluding cases with inadequate follow-up and juvenile granulosa cell tumor, 69 patients were analyzed. The average age at diagnosis was 48.3 years (21.2-86.0). 82.6% of patients had stage I disease; the remainder had stage II (8.7%) or stage III (8.7%) disease. 15 of 69 patients (21.7%) were treated for recurrent disease. The average time to recurrence was 6.27 years (range 1.05-20.71). There was a significant correlation between optimal resection or staging (including omentectomy and peritoneal biopsies) and recurrence (OR 0.171, 95% CI 0.0553-0.560, p=0.0076). Fertility preservation was not associated with recurrence (p=0.08). 71% of women with recurrent disease underwent secondary cytoreduction. Secondary CRS was associated with a significantly higher progression free survival compared to medical management alone at time of recurrence (median 2.3 vs 1.6 yrs, p=-0.01). 10 women were subsequently treated for a second recurrence; 50% were treated with cytoreductive surgery. No PFS benefit was seen with surgical management compared to medical management for the second recurrence (p=0.31). Seven women were then treated for a third recurrence or progression and six women for a fourth. PFS after treatment for second, third, or fourth recurrence or progression was longer among patients whose treatment included surgery compared to those who did not (median 1.708 vs 0.997 years), although this difference was not statistically significant. Conclusions: Complete staging for granulosa cell tumors was associated with decreased risk of recurrence. Secondary CRS at first recurrence is associated with a significantly higher progression free survival.

Tertiary cytoreductive surgery by laparoscopy in granulosa cell tumor recurrence

Granulosa cell tumors are diagnosed in stage I in 95% of cases, with a rate of recurrence as high as 10–64%.[1][1] The most common management of granulosa cell tumor recurrence...

Cytoreductive surgery followed by HIPEC repetition for secondary ovarian cancer recurrence.

Secondary and tertiary cytoreductive surgery was associated with improved overall survival in platinum-sensitive recurrent ovarian cancer (ROC). Hyperthermic intraoperative intra-peritoneal chemotherapy (HIPEC) is considered an attractive method in the treatment of ROC to deliver chemotherapy with enhanced effect directly at the tumor site. However, another deserving aspect is the feasibility and the oncologic role of HIPEC repetition. Twelve patients affected by secondary ovarian cancer recurrence previously submitted to cytoreduction followed by HIPEC were enrolled for the present study to receive tertiary cytoreduction followed by HIPEC repetition. The median operative time, including time for HIPEC procedure, was 360min (range 240-540). Average EBL was 325ml (from 100 to 500ml). The median hospital stay was of 5days, from 4 to 10. Low-grade post operatory complications occurred in 2 patients (16.6%) and high-grade complication in 1 case (8.3%). Our study report encouraging data about safety of HIPEC repetition in ovarian cancer treatment.

Tertiary Cytoreductive surgery in a Case of Platinum Sensitive Recurrent Ovarian Cancer

Tertiary Cytoreductive surgery in a Case of Platinum Sensitive Recurrent Ovarian Cancer

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study

ObjectivesTo evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. MethodsA multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. ResultsA total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I–II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31–58) compared to those with residual tumor (median OS: 33months, 95% CI 28–46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. ConclusionsThis is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Tertiary Cytoreduction for Recurrent Epithelial Ovarian Cancer: a Multicenter Study in Turkey.

The purpose of this study was to determine the benefit of tertiary cytoreductive surgery (TC) for secondary recurrent epithelial ovarian cancer (EOC), focusing on whether optimal cytoreduction has an impact on disease-free survival, and whether certain patient characteristics could identify ideal candidates for TC. Retrospective analysis of secondary recurrent EOC patients undergoing TC at three Turkish tertiary institutions from May 1997 to July 2014 was performed. All patients had previously received primary cytoreduction followed by intravenous platinum-based chemotherapy and secondary cytoreduction for first recurrence. Clinical and pathological data were obtained from the patients' medical records. Survival analysis was caried out using the Kaplan Meier method. Actuarial curves were compared by the two tailed Logrank test with a statistical significance level of 0.05. Median age of the patients was 49.6 years (range, 30-67) and thirty-eight (72%) had stage III-IV disease at initial diagnosis. Twenty six (49%) had optimal and 27 (51%) suboptimal cytoreduction during tertiary debulking surgery . Optimal initial cytoreduction, time to first recurrence, optimal secondary cytoreduction, time interval between secondary cytoreduction and secondary recurrence, size of recurrence, disease status at last follow-up were found to be significant risk factors to predict optimal TC. Optimal cytoreduction in initial and tertiary surgery and serum CA-125 level prior to TC were independent prognostic factors on univariate analysis. Our results and a literature review clearly showed that maximal surgical effort should be made in TC, since patients undergoing optimal TC have a better survival. Thus, patients with secondary recurrent EOC in whom optimal cytoreduction can be achieved should be actively selected.

Pancreatic resections as part of debulking surgery for relapsed epithelial ovarian cancer – a single center experience

Aims: To demonstrate the effectiveness and safety of pancreatic resections as part of cytoreductive surgery for relapsed epithelial ovarian cancer. Material and methods: Data of patients submitted to cytoreductive surgery for relpaed epithelial ovarian cancer in “Dan Setlacec” Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute between January 2002 and May 2015 were retrospectively reviewed. Results: Five patients were considered eligible for the study. In four cases distal pancreatectomy was performed as part of secondary cytoreduction while in the fifth case a spleno-pancreatectomy was performed at the moment of tertiary cytoreduction. Postoperatively a single patient developed a pancreatic leak which was successfully managed in a conservative manner. A median overall survival of 36 months was reported after secondary cytoreduction while the patient submitted to pancreatic resection as part of tertiary cytoreductive surgery experienced a 10 months survival, the patient being dead of disease at the time of ending the study. Conclusions: Pancreatic resections can be safely introduced as part of the therapeutic armamentarium for relapsed epithelial ovarian cancer.

Outcomes and patterns of secondary relapse in platinum-sensitive ovarian cancer: Implications for tertiary cytoreductive surgery

To evaluate the outcomes and patterns of patients with secondary relapsed ovarian cancer. A retrospective study was conducted. The cases comprised 83 patients who underwent tertiary cytoreductive surgery (TCS) followed by chemotherapy, whereas the controls consisted of 76 patients who received chemotherapy alone. The median survival was 20 months in 159 patients. Patients with microscopic residual disease after TCS had a median survival of 32.9 months compared with 14.6 months in those with macroscopic residual disease [hazard ratio (HR), 2.82; P = 0.001) and 15.0 months in patients with chemotherapy alone (HR, 2.23; P = 0.001). When stratified by a progression-free interval (PFI) after secondary cytoreduction (SCR), TCS showed no benefit in patients with a PFI ≤12 months or a PFI >12 months compared with those with chemotherapy alone. TCS improved survival in patients with recurrent disease in the pelvis compared with those with recurrent disease in the middle or upper abdomen, with a median survival of 34.9 months and 14.6 months, respectively (HR, 2.94; P = 0.010). However, TCS was not a survival determinant by multivariate analysis. A multivariate analysis identified a PFI after SCR (≤12 mos vs. >12 mos; HR, 2.34; 95% CI, 1.29-4.24; P = 0.005), mesenteric lymph node metastasis at SCR (yes vs. no; HR, 4.18; 95% CI, 1.93-9.03; P < 0.001) and treatment arms at secondary relapse (chemotherapy alone vs. TCS; HR, 1.56; 95% CI, 1.03-2.38; P = 0.037) as independent predictors of survival. Limited survival benefit from tertiary cytoreductive surgery was observed in patients with platinum-sensitive secondary relapsed ovarian cancer.

Value of Tertiary Cytoreductive Surgery in Epithelial Ovarian Cancer: An International Multicenter Evaluation

The value of surgery for recurrent epithelial ovarian cancer (OC) is controversial. The aim of the present study was to evaluate the outcome of EOC-patients who underwent tertiary cytoreductive surgery (TCS) and to identify prognostic markers for complete tumor resection and survival. Retrospective multicenter evaluation of TCS patients treated between 1997 and 2011 in 14 centers across Europe, the United States, and Asia. We evaluated 406 patients (median age, 55years; range, 16-80years). Median time from first to second recurrence was 18months (2-204months). Median follow-up from TCS was 14months (0-182months), and median OS was 26months (95% CI, 19.62-32.38months). Median OS for patients without versus any tumor residuals was 49months (95% CI, 42.5-56.4months) versus 12months (95% CI 9.3-14.7months) (p<0.001). The majority of the patients had an advanced initial FIGO stage III/IV (69%), peritoneal carcinomatosis (51.7%), and absence of ascites (72.2%). A total of 224 patients (54.1%) underwent complete tumor resection. The most frequent tumor dissemination site was the pelvis (73%). Rates of major operative morbidity and 30-day mortality were 25.9% and 3.2%, respectively. Multivariate analysis identified platinum resistance, tumor residuals at secondary surgery, and peritoneal carcinomatosis to be of predictive significance for complete tumor resection, while tumor residuals at secondary and tertiary surgery, decreasing interval to second relapse, ascites, upper abdominal tumor involvement, and nonplatinum third-line chemotherapy significantly affected OS. In this largest known database for TCS, residual tumor retains its high impact on survival even in the tertiary setting of OC. In specialized centers high rates of complete tumor resection can be obtained. Prospective analyses are warranted to define the value of TCS in EOC.

Clinical Outcome of Tertiary Surgical Cytoreduction in Patients with Recurrent Epithelial Ovarian Cancer

The value of tertiary cytoreductive surgery (TCS) on overall survival (OS) of patients with relapsed epithelial ovarian cancer (ROC) is not well defined. Aim of the present study was to evaluate the operative and clinical outcome after TCS. We systematically evaluated all consecutive patients undergoing TCS. Tumor dissemination pattern, operative morbidity, residual tumor, and survival are described based on a validated intraoperative documentation tool. Predictors of survival and complete tumor resection are analyzed with Cox regression or logistic regression models. Between October 2000 and December 2008, 135 patients (median age, 51 years; range, 22-80 years) of mainly initial FIGO stage ≥ III (106 patients, 78.5%) were evaluated. In 53 patients (39.3%) a complete tumor-resection was obtained. The 1-month operative mortality was 6%. During a median follow-up period of 9.6 months (range, 0.1-75 months), 78 patients (57.8%) died, while 52 patients (38.5%) experienced a further relapse. Median OS was 19.1 months for the total collective (95% confidence interval [95% CI], 14.84-23.35). Median OS was 37.8 months (95% CI, 12.7-62.7) for patients without residual tumor; versus 19.0 months (95% CI, 9.8-28.2) for residual tumor ≤ 1 cm and 6.9 months (95% CI, 3.05-10.7) for residual tumor > 1 cm (P < .001). The presence of peritoneal carcinomatosis did not seem to significantly affect OS. Complete tumor resection was identified as the strongest predictor of OS. Other independent predictors of OS were interval to primary diagnosis ≥ 3 years (hazard ratio [HR], 0.28; 95% CI, 0.14-0.59) and serous papillary histology (HR, 0.23; 95% CI, 0.09-0.56). A total of 42 patients (31.1%) presented at least 1 major complication. Multivariate analysis identified tumor involvement of the middle abdomen and peritoneal carcinomatosis as independent predictors of complete tumor resection. Postoperative tumor residual disease remains the strongest predictor of survival even in TCS setting. To identify the optimal candidates for TCS, the predictive value of ascites and peritoneal carcinomatosis should be confirmed by future prospective trials.

A third evaluation of tertiary cytoreduction

To evaluate the impact of tertiary cytoreductive surgery (TCS) on patient survival and to determine predictors of optimal TCS. Twenty patients with recurrent epithelial ovarian carcinoma who had TCS at Hacettepe University Hospital during 1992-2004 were retrospectively reviewed. Tertiary cytoreductive attempt was successful (optimal defined as <2 cm residual) in 12 patients and suboptimal in the remaining eight patients. Seven patients had no macroscopic residual, five patients had <2 cm gross residual and remaining 8 patients had >or=2 cm gross residual disease. Of these alive patients, 10 patients were alive with metastatic disease and only three patients were alive without any evidence of disease. Three patients had operative morbidity (15%), all of which were mild-moderate degree. Multivariate analysis could not differentiate a unique significant factor to have a possible predictor effect of optimal TCS. Multivariate survival analysis also could not differentiate any factor to have significant effect upon patient survival, neither the outcomes of primary, secondary or tertiary cytoreductive surgeries nor the usage of preoperative or postoperative chemotherapies. TCS may not be helpful for patient survival. Neither of the clinical factors predicted an optimal TCS. Further larger series are needed for a definite conclusion.

Tertiary cytoreductive surgery in recurrent ovarian cancer: Selection criteria and survival outcome

Tertiary cytoreductive surgery in recurrent ovarian cancer: Selection criteria and survival outcome

Tertiary cytoreductive surgery in recurrent ovarian cancer: Selection criteria and survival outcome

Studies of tertiary cytoreductive surgery (TCS) in recurrent epithelial ovarian cancer are limited, and appropriate patient selection remains a clinical challenge. We sought to evaluate the impact of TCS on survival and to determine predictors of optimal tertiary resection. Between January 1997 and July 2004, 47 women with recurrent epithelial ovarian cancer underwent TCS at two institutions. All patients received initial platinum and taxane-based chemotherapy following primary cytoreductive surgery. Clinico-pathologic factors and survival were retrospectively abstracted from medical records. Optimal TCS was defined as microscopic residual disease. Thirty of 47 (64%) patients underwent optimal TCS. Size of tumor implants<5 cm on preoperative imaging was the only significant predictor of achieving optimal TCS. Overall survival after TCS was statistically longer in patients with microscopic versus macroscopic residual disease (24 versus 16 months, p=0.03). After controlling for age, time to progression and optimal TCS, only the presence of diffuse disease at tertiary exploration remained a significant poor predictor of survival. However, in a cohort of patients with limited disease implants, multivariate analysis indicated that optimal TCS retained prognostic significance as a positive predictor of survival. Twelve patients (26%) experienced severe postoperative complications, including six with pulmonary embolism, four with fistulae and two with postoperative myocardial infarctions. Size of disease implants on preoperative imaging may guide the selection of candidates for TCS. In those patients with limited disease implants at laparotomy, optimal TCS is associated with improved survival.