Results of cytoreductive surgery for advanced and recurrent ovarian neoplasms and papillary serous carcinomas of the peritoneum

The aim of our study was to review and show the long-term results of the cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinomas of the peritoneum. We wanted to find clinical factors and in this way to select patients who can benefit from this kind of treatment. The clinical data of 32 patients searched retrospectively are presented in our research work. In 29 patients was possible radical cytoreductive surgery. Neoadjuvant and early postoperative chemotherapy were applied in most of the patients. The median follow up after cytoreductive surgery was 50 months. The overall median survival after cytoreduction was 38.5 months. We consider the cytoreductive surgery to be effective only when combined with neoadjuvant or with early postoperative chemotherapy. The surgical approach without chemotherapy leads to bad results.     

Long-term survival in advanced ovarian carcinoma following cytoreductive surgery with standard peritonectomy procedures

The impact of cytoreductive surgery with standard peritonectomy procedures has not been extensively assessed in the treatment of advanced ovarian cancer. The aims of the study are to report the long-term results of patients with advanced ovarian cancer undergoing cytoreductive surgery with standard peritonectomy procedures and to identify the prognostic indicators that may affect outcome. The records of 74 women with advanced ovarian cancer were retrospectively reviewed. Clinical indicators were correlated to survival. The hospital mortality and morbidity rates were 13.5% and 28.4%, respectively. Complete or near-complete cytoreduction was possible in 78.4% of the patients. Overall 10-year survival rate was 52.5%. Complete cytoreductive surgery, small-volume tumor, low-grade tumor, the absence of distant metastases, the use of systemic adjuvant chemotherapy, performance status >70%, and limited extent of peritoneal carcinomatosis were favorable indicators of survival. Complete cytoreduction (P= 0.000) and treatment with systemic chemotherapy (P= 0.001) independently influenced survival. Recurrence was recorded in 37.8% of the patients and was independently influenced by the tumor grade (P= 0.037). Cytoreductive surgery with standard peritonectomy procedures followed by adjuvant chemotherapy offers long-term survival in women with advanced ovarian cancer who have limited peritoneal carcinomatosis and no distant and irresectable metastases.     

Long-term survival after paclitaxel plus platinum-based combination chemotherapy for extraovarian peritoneal serous papillary carcinoma: is it different from that for ovarian serous papillary cancer?

The purpose of this study was to compare the effect of paclitaxel plus platinum-based chemotherapy in the treatment of extraovarian peritoneal serous papillary carcinoma (EPSPC) and ovarian serous papillary cancer (OSPC). Only the patients treated with initial surgery plus postoperative adjuvant chemotherapy and having FIGO stage IIIC disease with omental and/or peritoneal involvement were analyzed. Thirty-two patients with EPSPC and 43 with OSPC were included in this study. The median age, mean CA-125, and volume of ascitis were higher in patients with EPSPC. There was no significant difference between the two groups with respect to other prognosticators. The median overall survival (OS) durations were 30 months (95% CI 24.8-35.3) in patients with EPSPC and 28 months (95% CI 21.1-34.9) in those with OSPC (P= 0.35). The 3-year OS rates in the patients and controls were 28% and 31%, respectively (P= 0.84). In patients with EPSPC, only optimal cytoreduction was significantly related to progression-free survival and OS durations as a prognostic factor. In the EPSPC group, 65.5% of the patients (19/29) had lymphatic involvement, compared to 88.4% (38/43) in the OSPC group (P= 0.02). As an adjuvant therapy, the paclitaxel plus platinum-based combination regimen had similar effects on survival in the EPSPC and OSPC groups.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial

Objective.

The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC).

Methods.

Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m²) for 6 cycles.

Results.

Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤ 2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2% (median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS.

Conclusions.

In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial.     

CA125 surveillance increases optimal resectability at secondary cytoreductive surgery for recurrent epithelial ovarian cancer

Objective

Recent data suggest that serial CA125 surveillance following remission in asymptomatic patients with epithelial ovarian cancer (EOC) does not impact overall survival. However, earlier detection of recurrence may influence resectability at secondary cytoreductive surgery (SCS). We hypothesized that a shorter time interval between CA125 elevation and SCS correlates with a higher likelihood of optimal resection among eligible patients.

Methods

We identified patients with recurrent epithelial ovarian cancer who underwent SCS from 1995 to 2009 at our institution. All patients initially underwent primary cytoreductive surgery followed by platinum-based chemotherapy. CA125 elevation was considered the first value two-times the patient's nadir level. Our “study interval” was the time between CA125 elevation and SCS. Optimal SCS was defined as microscopic residual disease (≤ 0.5 cm). Our analysis compared patients who underwent optimal vs. suboptimal SCS.

Results

Seventy-four patients who underwent SCS for recurrent EOC met inclusion criteria. Median disease-free interval prior to SCS was 19 vs. 12 months for the optimal and suboptimal SCS groups. More patients undergoing suboptimal SCS had ascites (21% vs. 2%, p = 0.01) and carcinomatosis (42% vs. 5%, p < 0.0001). Patients who underwent optimal SCS went to the operating room 5.3 vs. 16.4 weeks (HR 1.03, 95% CI 1.01-1.06, p = 0.04) from the time of their CA125 elevation. Optimal SCS was associated with a longer overall survival (47 vs. 23 months, p < 0.0001).

Conclusions

Each week delay after first CA125 elevation correlated with a 3% increased chance of suboptimal resection at SCS. Serial CA125 surveillance for early detection of recurrence may increase rates of optimal SCS and potentially influence overall survival.     

Cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma

OBJECTIVE: This study aims to identify favorable preoperative characteristics and examine the impact of secondary cytoreductive surgery on survival for patients with recurrent epithelial ovarian carcinoma. METHODS: Patients who underwent cytoreductive surgery for recurrent epithelial ovarian cancer were identified in our surgical database for the period 1988-2004. Patient charts were reviewed and data collected regarding patient demographics, surgical management, preoperative evaluation, perioperative complications, and oncologic outcome. RESULTS: Eighty-five patients met eligibility criteria. Preoperative factors that correlated with improved survival were disease-free interval of greater than 12 months (p<0.01) and residual disease after primary surgery of <2 cm (p<0.02). Other preoperative factors evaluated but not found significant included radiographic findings, physical findings, previous histology, stage, grade, previous chemotherapy, prior recurrence, and serum CA-125 level. Optimal resection to <1 cm residual disease was achieved in 86% of patients who had secondary cytoreduction. Small bowel and colon resection for cytoreduction occurred in 7% and 51% of patients, respectively. Operative complications occurred in 14% and postoperative complications occurred in 21% of patients. The median survival of patients who were optimally cytoreduced to <1 cm was 30 months compared to 17 months for patients with residual disease>or=1 cm (p<0.05). Operative factors that were evaluated and did not significantly effect survival were location of recurrence, presence of ascites, and extent of recurrence. Recurrent or progressive disease occurred in 75% of patients during follow-up. CONCLUSION: When selecting patients for secondary cytoreduction, the most significant preoperative factors are disease-free interval and success of a prior cytoreductive effort. Once secondary cytoreductive surgery is attempted, the most important factor for improved survival is optimal cytoreduction. Of equal importance is counseling regarding the significant risk for bowel surgery, colostomy, and complications.     

Cost effectiveness of neoadjuvant chemotherapy followed by interval cytoreductive surgery versus primary cytoreductive surgery for patients with advanced stage ovarian cancer during the initial treatment phase

Objective

Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective.

Cytoreductive surgery and HIPEC after neoadjuvant chemotherapy for advanced epithelial ovarian cancer

AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage IIIC-IV epithelial ovarian cancer (EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modified Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy (ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy. RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up. CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.     

Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma

Scarabelli C, Gallo A, Campagnutta E, Carbone A. Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma. Int J Gynecol Cancer 1998; 8 : 215–221.
Splenectomy is occasionally indicated to achieve optimal cytoreduction during surgery for epithelial ovarian cancer. Between January 1989 and December 1996, 40 epithelial ovarian cancer patients underwent splenectomy: 14 patients during primary surgery and 26 during secondary cytoreductive surgery. Splenectomy was performed for tumor reduction in 34 patients (85 %) and for iatrogenic injury in six patients (15%). The spleen was removed because of parenchymal splenic metastases in nine patients (22.5 %), significant hilar and/or capsular disease in 10 patients (25 %), and perisplenic disease in 15 patients (37.5%). The histopathological diagnosis of the resected spleens showed microscopic hilar disease in four patients who had the spleen removed because of iatrogenic injury and no disease in only two patients. Splenectomy could be carried out with an acceptable morbidity. Left-sided pleural effusion was the most frequent complication. The estimated two-year survival rate for patients who underwent splenectomy during primary surgery with no residual disease and <2 cm intraperitoneal residual disease was 83% and 42%, respectively. Nine of these patients (64.3%) had recurrent disease. The median time to recurrence was 11 months (range 5–18). The estimated two-year survival rate for patients who underwent splenectomy during secondary surgery with no residual disease and <2 cm intraperitoneal residual disease was 78% and 24%, respectively. The estimated three-year survival rate was 0% for all these patients. The results of the present study show that splenectomy, if necessary to achieve optimal debulking, should be considered in previously untreated patients with no intraperitoneal residual disease and in patients with late (>1 year) recurrent disease.     

Long-term survival after chemotherapy for advanced epithelial ovarian carcinoma

Four hundred twenty-nine patients were entered into four prospective randomized clinical studies between January 1, 1973, and July 1, 1979. The records of 395 of these were analyzed to determine the proportion of patients surviving 48 months after therapy initiation. Ninety-six patients (24%) were living at 48 months, 89 of whom had second-look laparotomies. Of the 96 living patients, 53 (55%) were clinically free of disease and 43 (45%) had disease. Combination-agent chemotherapy produced a larger proportion of 48-month survivors than single-agent therapy (P = 0.001); 70% of these survivors were clinically free of disease. Patient characteristics, such as age, International Federation of Gynaecology and Obstetrics (FIGO) stage, histologic grade of tumor, and amount of residual tumor present prior to chemotherapy exerted a strong influence on length of survival. Long-term survival was not totally dependent on a complete response to chemotherapy; in fact, persistent treatment with drug regimens induced bone marrow disorders and death due to toxicity in five patients. The continued fall in survival curves after 48 months suggests that current therapy regimens are not dramatically changing long-term survival rates.     

Advances in the management of advanced and recurrent uterine papillary serous carcinoma

Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer that accounts for 5–10% of all cases. Over 50% of the patients with UPSC present with advanced stage disease ⁽¹⁾ . Among patients with noninvasive uterine disease, 40% have advanced stage UPSC ⁽¹⁾ ; therefore, complete surgical staging is crucial to determine prognosis and treatment ⁽²⁾ . Optimal tumor debulking (<1cm) is associated with a better prognosis and improved overall survival ⁽³⁾ . After initial surgical staging, patients with high stage UPSC have an improved overall survival if treated with chemotherapy (platinum-based or paclitaxel-based therapy) ⁽¹⁾ . Even with chemotherapy, the disease free interval is approximately 1 year ^(4–6) . The role of radiation in these patients is unclear. Up to 30% of recurrences occur outside of the abdomen and pelvis (unpublished data). While the response rate to chemotherapy in the recurrent setting is up to 80%, the duration of response is approximately 7 months ^(4–6) . Because the disease free interval in the adjuvant setting and the duration of response in patients with recurrent disease is limited, better strategies are needed to treat patients with this disease. We have recently evaluated Her-2/neu overexpression and amplification in a series of patients with UPSC. Her-2/neu overexpression was independently associated with a poor prognosis, however the rate of specific gene amplification was only 3% ⁽⁷⁾ . We have found that imatinib-targeted kinases are overexpressed in UPSC ⁽⁸⁾ . We currently are evaluating imatinib (Gleevec, Novartis) and paclitaxel for the treatment of UPSC in patients with advanced or recurrent disease.