Optimal Primary Cytoreductive Surgery Research Articles

Cost-effectiveness of hyperthermic intraperitoneal chemotherapy at primary cytoreduction of epithelial ovarian cancer based on residual disease status

Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin when used at the time of interval cytoreductive surgery (ICS) after neoadjuvant chemotherapy (NACT) has been shown to provide a survival advantage compared to interval cytoreduction alone for patients with advanced epithelial ovarian cancer in a cost-effective manner. A recent large multi-center retrospective cohort study showed a survival advantage with HIPEC given during primary debulking surgery compared to surgery alone. While there is an ongoing randomized controlled trial examining HIPEC at the time of primary cytoreductive surgery (PCS) before chemotherapy (OVHIPEC-2), there is currently no study of this practice in the United States or cost data to inform incorporation of this practice. To help guide the use of HIPEC in the upfront setting until the results of the OVHIPEC-2 are available in 2026, a decision-analytic cost-effectiveness model of the US healthcare sector was developed for patients undergoing PCS with or without HIPEC. Effectiveness inputs were extracted from a Chinese retrospective cohort study of 425 patients who underwent PCS with HIPEC and 159 patients who underwent PCS alone. We found incremental cost effectiveness ratios (ICER) of $9,789 per life year saved (LYS) for optimal PCS, $18,164/LYS for suboptimal PCS, and $7,854/LYS for all patients. Our findings provide preliminary data to support that HIPEC at the time of primary cytoreductive surgery can be considered cost-effective regardless of residual disease status when using a standard willingness to pay threshold.

Evaluation of results of combined treatment in patients with disseminated ovarian cancer

Background. According to the modern concept of surgical treatment of ovarian cancer (OC) it is necessary to perform cytoreductive surgery (CRS) without residual tumor in order to achieve more favorable oncological prognoses. However, the possibilities of achieving it with a disseminated process (stages IIIIV) are limited, and therefore, for some patients, neoadjuvant chemotherapy (NACT) is the optimal initial treatment.
 Aim. To compare the duration of progression-free survival (PFS) of patients with advanced OC after treatment, as well as to assess the value of the prognostic nutritional index (PNI) in predicting this outcome.
 Materials and methods. We conducted a retrospective cohort study of 78 patients with stages IIIIV OC, who received combined treatment between January 2016 and March 2020 (54 patients after primary CRS (PCRS)+platinum-based chemotherapy (CT), 24 patients after NACT+interval CRS (ICRS)+postoperative CT. The predictive value of the PNI was calculated.
 Results. The complete PCRS is associated with increased PFS: after complete PCRS 3211.21 months (95% confidence interval CI 10.0953.97); after optimal PCRS 223.46 months (95% CI 15.2128.79); after suboptimal PCRS 147 months (95% CI 0.2827.72). Performing a complete ICRS is associated with decreased PFS compared to PCRS, even if the complete CRS is achieved: after complete ICRS 143.34 months (95% CI 7.4620.54); after optimal ICRS 172.16 months (95% CI 12.7721.23); after suboptimal ICRS 7 months. PNI27.86 correlates with an increased probability of complete PCRS in patients with advanced PCR (AUC 94.3, sensitivity 80%, specificity 91.7%; p0.001).
 Conclusion. Achieving complete PCRS in patients with disseminated OC leads to an improvement in the oncological outcome. The prognostic value of pre-treatment calculation of PNI has been revealed: an increased PNI is associated with more favorable perioperative outcomes. Objective criteria should be developed for a strictly reasoned refusal to carry out the first stage of surgical treatment due to the obviously less favorable prognosis of the tactics of "NACT+ICRS+CT".

Incidence and prognostic significance of inguinal lymph node metastasis in women with newly diagnosed epithelial ovarian cancer

Objective(s)To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis. MethodsAn IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as >1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed. ResultsOf the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24). Conclusion(s)In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.

The impacts of neoadjuvant chemotherapy and of cytoreductive surgery on 10-year survival from advanced ovarian cancer.

To compare the long-term survival outcomes for women with advanced ovarian cancer treated with chemotherapy either before or after surgery (neoadjuvant chemotherapy vs primary cytoreductive surgery) at a single tertiary cancer center. Retrospective cohort study of 326 patients with Stage IIIC or IV high-grade serous ovarian cancer who received neoadjuvant chemotherapy or primary cytoreductive surgery between 2001 and 2011. Clinical treatments were recorded and 10-year survival rates were measured. A total of 183 women (56.1%) underwent primary cytoreductive surgery and 143 women (43.9%) received neoadjuvant chemotherapy. Women who received neoadjuvant chemotherapy were more likely to have no residual disease than those who underwent primary cytoreductive surgery (51.4% vs 41.5%; P=0.030) but experienced inferior 10-year overall survival (9.1% vs 19.3%; P<0.001). Among those who had primary cytoreductive surgery, those with no residual disease had superior 10-year overall survival than those who had any evidence of residual disease (36.0% vs 7.2%; P<0.001). Among women with advanced ovarian cancer, those who underwent primary cytoreductive surgery had better survival than those who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy should be reserved for those in whom optimal primary cytoreductive surgery is not feasible.

2-Octyl cyanoacrylate for the prevention of anastomotic leak

Objective: Optimal primary cytoreductive surgery for patients with advanced ovarian cancer may require bowel resection. Anastomotic leak following colorectal surgery is a significant cause of morbidity and mortality. The aim of this study was to evaluate the impact of a reinforced colo-colonic anastomosis with tissue adhesive, 2-octylcyanoacrylate (2-O), on the integrity of anastomotic healing as measured by anastomotic bursting pressure (ABP).

Prognostic factors for maximally or optimally cytoreduced stage III nonserous epithelial ovarian carcinoma treated with carboplatin/paclitaxel chemotherapy.

To identify factors predictive of poor prognosis in women with stage III nonserous epithelial ovarian cancer (EOC) who had undergone maximal or optimal primary cytoreductive surgery (CRS) followed by six cycles of intravenous carboplatin/paclitaxel chemotherapy. A multicenter, retrospective department database review was performed to identify patients with stage III nonserous EOC who had undergone maximal or optimal primary CRS followed by six cycles of carboplatin/paclitaxel chemotherapy at seven gynecological oncology centers in Turkey. Demographic, clinicopathological and survival data were collected. A total of 218 women met the inclusion criteria. Of these, 64 (29.4%) patients had endometrioid, 61 (28%) had mucinous, 54 (24.8%) had clear-cell and 39 (17.9%) had mixed epithelial tumors. Fifty-five (25.2%) patients underwent maximal CRS, whereas 163 (74.8%) had optimal debulking. With a median follow-up of 31.5 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 34.8% and 44.2%, respectively. Bilaterality (hazard ratio [HR] 1.44, 95% CI 1.01-2.056; P = 0.04), age (HR 2.25, 95% CI 1.176-4.323; P = 0.014) and maximal cytoreduction (HR 0.34, 95% CI 0.202-0.58; P < 0.001) were found to be independent prognostic factors for PFS. However, age (HR 2.6, 95% CI 1.215-5.591; P = 0.014) and maximal cytoreduction (HR 0.31, 95% CI 0.166-0.615; P < 0.001) were defined as independent prognostic factors for OS. The extent of CRS seems to be the only modifiable prognostic factor associated with stage III nonserous EOC. Complete cytoreduction to no gross residual disease should be the main goal of management in these women.

A Theoretical View of Ovarian Cancer Relapse

Ovarian cancer (OC) is a disease that almost invariably relapses even after optimal primary cytoreductive surgery and standard first-line platinum-based chemotherapy. After recurrence, progressions occur at shorter intervals in the natural history of the disease. However, the biologic and cellular events underlying recurrence and progression (maintenance phase) are yet to be completely understood. Ovarian adenocarcinoma, like any other tissue, after reduction of the cell population (cytoreduction) either by surgery, chemotherapy, radiotherapy, or targeted therapies induced cell-death, tends to its own renewal through cancer stem cells (CSC). CSC remain quiescent most of their lives and then ‘wake up’, generating a proliferative progeny that differentiates as they become different clones of daughter cells. What defines them is their ‘self-renewal’ potential, thus perpetuating the disease with higher tumour volume relapses in which CSC increase in number. We propose a theory of how recurrence/relapse occurs in which CSC play a key role in the genesis of relapse. These self-renewing CSC can generate a proliferative progeny and this population is sensitive to chemotherapy, anti-angiogenic agents, and PARP inhibitors, which so far have only increased the disease/relapse free survival (‘maintenance phase’). In OC it seems we are not addressing the ‘root’ of recurrence/relapse. As with any theory, this is based on both proven facts and suggested hypotheses, which may serve as investigation drivers towards finally making a substantial improvement in OC management.

The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the accurate pathologic diagnosis of epithelial ovarian cancer.

The evolving role of cytopathology in the era of neoadjuvant chemotherapy for the accurate pathologic diagnosis of epithelial ovarian cancer.

Cited rationale for variance in the use of primary intraperitoneal chemotherapy following optimal cytoreduction for stage III ovarian carcinoma at a high intraperitoneal chemotherapy utilization center

ObjectiveStudies have demonstrated improved ovarian cancer survival with the administration of a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy following optimal cytoreduction. Despite this, IV/IP chemotherapy is not uniformly used. In this retrospective cohort study, we assessed the documented reasons for giving IV-only chemotherapy. MethodsAll patients who had optimal primary cytoreductive surgery for stage III ovarian, fallopian tube, or primary peritoneal carcinoma, met eligibility criteria for GOG-172, and received primary chemotherapy at our institution between 2006 and 2013 were identified. Patients who received at least one cycle of adjuvant IV/IP therapy were included in the IP group. Patient characteristics, treatment information, and reason cited for not administering IP therapy were collected. ResultsOf the patients evaluated, 330 met inclusion criteria. The majority (n=261, 79%) received at least one IV/IP cycle (median, 6; range, 1–6), and 62% completed 6cycles. The most common reason for giving IV-only therapy was postoperative status (i.e., delayed wound healing, performance status), accounting for 18 (26%) of the 69 IV-only patients (5% of the entire cohort). Other cited reasons were baseline comorbidities (15%) and IP port complications (12%). Receipt of ≥1cycle of IP chemotherapy (HR 0.51; 95% CI, 0.32–0.80) and no gross residual disease (HR 0.47; 95% CI, 0.31–0.71) were associated with improved overall survival. ConclusionPotentially modifiable factors identified as leading to the use of IV-only chemotherapy were postoperative status and IP port complications, which if altered, could potentially lead to increased IP chemotherapy use.

Anesthetic Selection and Disease-Free Survival Following Optimal Primary Cytoreductive Surgery for Stage III Epithelial Ovarian Cancer

Previous studies have offered conflicting results regarding an association between perioperative epidural analgesia and disease-free survival (DFS) following optimal primary cytoreductive surgery for stage III epithelial ovarian cancer. A possible separate role for inhalational anesthetics has not been assessed. We conducted a historical cohort study of all women undergoing optimal primary cytoreduction (<1 cm residual disease) for Stage III epithelial ovarian cancer between January 1, 2007, and December 31, 2011, at Brigham and Women's Hospital. Cohorts were defined by exposure to perioperative epidural analgesia or exposure to specific volatile anesthetics. The primary outcome was DFS. A total of 194 patients met study inclusion criteria. Addition of epidural analgesia was associated with a lower overall rate of ovarian cancer recurrence compared with general anesthesia alone (72 vs. 85 %, p = 0.028). Longer median DFS was associated with more than 48 h of epidural use (14.9 months) compared with fewer than 24 h (10.9 months) or 24-48 h of epidural use (10.0 months; p = 0.025). Use of desflurane was associated with a lower overall rate of ovarian cancer recurrence compared with sevoflurane (63 vs. 84 %, p = 0.01). In multivariate analysis, use of desflurane was independently associated with improved DFS (hazards ratio 0.563; 95% confidence interval 0.33-0.962). For patients with Stage III ovarian cancer, use of desflurane is associated with improved DFS following primary cytoreductive surgery compared with other volatile anesthetics. If epidural analgesia offers additional benefit, this effect appears limited to patients with more than 48 h of postoperative epidural use.

Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma?

ObjectiveOptimal surgical outcome has been proved to be one of the most powerful survival determinants in the management of ovarian cancer patients. Actually, for ovarian cancer patients there is no general consensus on the preoperatively establishment of cytoreducibility. MethodsBetween January 2011 and June 2012 patients affected by suspicious advanced ovarian cancer, referred to the Department of Gynecology of Campus Biomedico of Rome were enrolled in the study. All patients had serum CA125 and HE4 measured preoperatively. After a complete laparoscopy to assess the possibility of optimal debulking surgery defined as no visible residual tumor after cytoreduction (RT=0), patients were submitted to primary cytoreductive surgery (Group A) or addressed to neoadjuvant chemotherapy (Group B). ResultsAfter diagnostic open laparoscopy, 36 patients underwent optimal primary cytoreductive surgery (Group A) and 21 patients were addressed to neoadjuvant chemotherapy (Group B). In our population, based on ROC curve, the HE4 value of 262pmol/L is the best cut-off to identify patients candidates to optimal cytoreduction with a sensitivity of 86.1% and a specificity of 89.5% (PPV=93.9% and NPV=77%). In addition, CA125 has a sensitivity of 58.3% and a specificity of 84% at cut-off of 414 UI/mL (AUC is 0.68, 95% C.I.=0.620 to 0.861). ConclusionOur data indicate that preoperative HE4 is a better predictor for optimal cytoreduction compared to CA125. The best combination in predicting cytoreduction is HE4≤262 pmol/L and ascites <500mL with a sensitivity of 100% and a specificity of 89.5% (PPV=94% and NPV=100%).

Optimal primary surgical treatment for advanced epithelial ovarian cancer.

Ovarian cancer is the sixth most common cancer among women. In addition to diagnosis and staging, primary surgery is performed to achieve optimal cytoreduction (surgical efforts aimed at removing the bulk of the tumour) as the amount of residual tumour is one of the most important prognostic factors for survival of women with epithelial ovarian cancer. An optimal outcome of cytoreductive surgery remains a subject of controversy to many practising gynae-oncologists. The Gynaecologic Oncology group (GOG) currently defines 'optimal' as having residual tumour nodules each measuring 1 cm or less in maximum diameter, with complete cytoreduction (microscopic disease) being the ideal surgical outcome. Although the size of residual tumour masses after surgery has been shown to be an important prognostic factor for advanced ovarian cancer, it is unclear whether it is the surgical procedure that is directly responsible for the superior outcome that is associated with less residual disease. To evaluate the effectiveness and safety of optimal primary cytoreductive surgery for women with surgically staged advanced epithelial ovarian cancer (stages III and IV).To assess the impact of various residual tumour sizes, over a range between zero and 2 cm, on overall survival. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3) and the Cochrane Gynaecological Cancer Review Group Trials Register, MEDLINE and EMBASE (up to August 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Retrospective data on residual disease from randomised controlled trials (RCTs) or prospective and retrospective observational studies which included a multivariate analysis of 100 or more adult women with surgically staged advanced epithelial ovarian cancer and who underwent primary cytoreductive surgery followed by adjuvant platinum-based chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm. Two review authors independently abstracted data and assessed risk of bias. Where possible, the data were synthesised in a meta-analysis. There were no RCTs or prospective non-RCTs identified that were designed to evaluate the effectiveness of surgery when performed as a primary procedure in advanced stage ovarian cancer.We found 11 retrospective studies that included a multivariate analysis that met our inclusion criteria. Analyses showed the prognostic importance of complete cytoreduction, where the residual disease was microscopic that is no visible disease, as overall (OS) and progression-free survival (PFS) were significantly prolonged in these groups of women. PFS was not reported in all of the studies but was sufficiently documented to allow firm conclusions to be drawn.When we compared suboptimal (> 1 cm) versus optimal (< 1 cm) cytoreduction the survival estimates were attenuated but remained statistically significant in favour of the lower volume disease group There was no significant difference in OS and only a borderline difference in PFS when residual disease of > 2 cm and < 2 cm were compared (hazard ratio (HR) 1.65, 95% CI 0.82 to 3.31; and HR 1.27, 95% CI 1.00 to 1.61, P = 0.05 for OS and PFS respectively).There was a high risk of bias due to the retrospective nature of these studies where, despite statistical adjustment for important prognostic factors, selection bias was still likely to be of particular concern.Adverse events, quality of life (QoL) and cost-effectiveness were not reported by treatment arm or to a satisfactory level in any of the studies. During primary surgery for advanced stage epithelial ovarian cancer all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (< 1 cm) residual disease. Due to the high risk of bias in the current evidence, randomised controlled trials should be performed to determine whether it is the surgical intervention or patient-related and disease-related factors that are associated with the improved survival in these groups of women. The findings of this review that women with residual disease < 1 cm still do better than women with residual disease > 1 cm should prompt the surgical community to retain this category and consider re-defining it as 'near optimal' cytoreduction, reserving the term 'suboptimal' cytoreduction to cases where the residual disease is > 1 cm (optimal/near optimal/suboptimal instead of complete/optimal/suboptimal).

Significance of hepatic resection in the treatment of hepatic parenchymal metastasis of recurrent epithelial ovarian carcinoma

To investigate the validity of hepatic resection as a treatment option for hepatic parenchymal metastasis in patients with recurrent epithelial ovarian cancer. A retrospective review of the clinicopathological and follow up data of 39 patients treated in our hospital from 1996 to 2008 was conducted. Ten patients underwent partial hepatic resection for metastatic ovarian cancer. All the 10 patients underwent surgery were with unilobar metastasis and the number of tumors was lower than 3(P < 0.05). No significant difference existed in patient age, the primary pathology type and tumor grade, the rate of optimal primary cytoreductive surgery, the disease free survival after the primary therapy and the serum CA125 level at the liver metastasis when compared with the 29 patients accepted salvage chemotherapy (P > 0.05). There were 7 patients who achieved optional surgery. The operation complication was 3/10 and there was no perioperative mortality. There were 2 patients without postoperative chemotherapy in the 8 recurrent patients with microscopic negative margins. The median recurrence time was 12 (5 - 24) months after the hepatic resection. The overall median survival periods after hepatic metastasis were 26 and 9 months and the 3-years cumulative survival rates were 60.0% and 16.8% for the optimal surgery patients including hepatic surgery and the salvage chemotherapy patients, respectively (P < 0.05). Hepatic resection for liver metastatic epithelial ovarian cancer is safe and may achieve long-term survival in patients after optimal second cytoreductive surgery.

The role of secondary cytoreductive surgery for recurrent mucinous epithelial ovarian cancer (mEOC)

Background Mucinous epithelial ovarian cancer (mEOC) may exhibit a distinct biological behavior in epithelial ovarian cancer (EOC). The role of secondary cytoreductive surgery was evaluated in patients with recurrent mEOC, and the prognosis was assessed. Methods Twenty-one patients with stages IIc to IV mEOC who experienced disease recurrence and received secondary cytoreductive surgery at Fudan University Cancer Hospital between Jan. 1997 and Dec. 2005 were retrospectively reviewed. Survival curves were generated using the Kaplan–Meier method and the significant comparison of survival rate was estimated by the log-rank test. Results The median progression-free interval (PFI) was 14 months (range, 5–46 months) after the first cytoreduction. Seven patients (33%) who received secondary cytoreductive surgery were optimally cytoreduced with residual disease less than or equal 1 cm, and the other 14 patients (67%) underwent suboptimal surgical cytoreduction. The overall median survival time was 27 months (range, 8–64 months). The median survival time after recurrence was 10 months (range, 3–32 months). There was no significant statistical difference in median survival between patients with optimal and suboptimal secondary surgical cytoreduction, with an estimated survival of 10 months and 9.8 months, respectively ( P > 0.05). Conclusion Optimal primary cytoreductive surgery for advanced mEOC was very important. Once it recurs, the prognosis is very poor. Patients with recurrent mEOC should be carefully assessed before performing secondary cytoreductive surgery, as this may have limited impact on the overall survival rates.

Survival impact of multiple bowel resections in patients undergoing primary cytoreductive surgery for advanced ovarian cancer: A case–control study

Objective. To evaluate clinicopathological factors and survival outcome of patients with advanced epithelial ovarian carcinoma undergoing multiple bowel resections to achieve optimal (≤ 1 cm) cytoreduction. Methods. A case–control study was performed identifying patients undergoing optimal primary cytoreductive surgery with ≥ 2 bowel resections between 10/1997 and 2/2006. The two control groups consisted of (1) patients undergoing optimal cytoreduction with ≤ 1 bowel resections matched [1:2] for age and stage and (2) patients left with suboptimal disease. Cox proportional hazards model were used to evaluate the effects of demographic and surgico-pathologic factors on survival outcome. Results. A total of 34 patients underwent ≥ 2 bowel resections. Sixty-eight patients underwent ≤ 1 bowel resections. All patients had optimal cytoreduction and 40/102 patients (39.2%) underwent complete cytoreduction. Patients undergoing multiple bowel resections experienced a higher EBL (700 v 500 mL, p = 0.01) and longer LOS (10 v 7 days, p = 0.01) compared to patients with ≤ 1 bowel resections. Multivariate analysis revealed the amount of residual disease to be a statistically significant and radiation therapy to the right pelvic sidewall and cul-de-sac independent predictor of overall survival. The median overall survival time for patients undergoing ≥ 2 bowel resections was 28.3 months, which was comparable to patients undergoing ≤ 1 bowel resections, (37.8 months, p = 0.09) but statistically significantly superior to patients left with suboptimal residual disease (12 months, p = 0.02). Conclusions. Although primary surgery that includes ≥ 2 bowel resections is associated with longer LOS and a higher EBL, such extensive procedures are warranted if they will contribute to an overall optimal residual disease state.

Intraperitoneal cisplatin and paclitaxel versus intravenous carboplatin and paclitaxel chemotherapy for Stage III ovarian cancer: A cost-effectiveness analysis

Objective. To evaluate the cost-effectiveness of intraperitoneal cisplatin and paclitaxel chemotherapy as front-line treatment for patients with Stage III epithelial ovarian cancer following optimal primary cytoreductive surgery. Methods. Based on Gynecologic Oncology Group protocols #172 and #158, a decision analysis model was created to compare two treatment strategies for patients with optimal residual disease Stage III ovarian cancer: (1) inpatient intravenous paclitaxel (24 h) and intraperitoneal cisplatin plus outpatient intraperitoneal paclitaxel chemotherapy (IP/IV), and (2) outpatient intravenous paclitaxel (3 h) and carboplatin chemotherapy (IV/IV). The cost-effectiveness of each strategy was evaluated from the perspective of society. Results. Cost-effectiveness analysis revealed that the strategy of IP/IV chemotherapy had an overall cost per patient of $39,861 and effectiveness of 5.16 QALYs compared to $18,822 and 4.59 QALYs for IV/IV chemotherapy. The IP/IV chemotherapy strategy was associated with an additional 0.56 QALYs at an incremental cost of $21,039. The incremental C/E ratio for IP/IV chemotherapy was $37,454/QALY. Inpatient treatment accounted for 43.2% of the cost of IP/IV chemotherapy. Sensitivity analysis testing confirmed the robustness of the model. Conclusions. In this model, IP/IV chemotherapy was associated with a modest extension in quality-adjusted survival time but was also more costly than IV/IV chemotherapy. On balance, the IP/IV strategy can be considered a good healthcare value. However, these data also suggest that efforts to reduce the cost of IP/IV chemotherapy, such as through development of an ambulatory regimen with equivalent therapeutic efficacy but an improved toxicity profile, would improve the overall value of this adjuvant treatment program.

Diagnostic Open Laparoscopy in the Management of Advanced Ovarian Cancer

Improved surgical techniques have led to agreement that optimal primary cytoreductive surgery (OPCS) is, along with adjuvant chemotherapy, the preferred management of advanced ovarian cancer (AOC). The best survival can be expected if no gross macroscopic disease is left behind, but there is considerable variation in reported rates of OPCS. This study evaluated diagnostic open laparoscopy (DOL) as a means of predicting the best candidates to undergo OPCS. DOL was carried out in 87 patients with newly diagnosed AOC. Those who were not considered candidates for OPCS received 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Among 87 women having DOL were 53 (61%) who were thought to be operable and who underwent primary cytoreductive surgery (group A). The remaining 34 patients (group B) had a partial clinical response and were scheduled to undergo IDS and receive neoadjuvant and then adjuvant chemotherapy. An attempt was made at DOL to systematically examine the entire abdominal cavity using atraumatic forceps. Major postoperative complications occurred in 9% of patients in group A and 4% of those in group B. The rate of optimal debulking, leaving behind no residual tumor, was 96% in patients in group A and 80% in group B. After a median follow up of 22 months, survival rates were 87% and 60% in groups A and B, respectively, and rates of survival with no evidence of disease were 49% and 27%, respectively. When patients in group B not having IDS were excluded, the survival rate was 81% in those with no residual tumor after debulking, and 36% of these patients in group B had no evidence of disease. Patients in group B who failed to respond to chemotherapy and therefore did not have IDS lived for a median of 7 months. Median times to progression were longer in patients in group A (10 months vs 6 months in group B). Rates of optimal debulking of AOC—eliminating gross residual tumor—have improved greatly with the advent of DOL. The investigators believe that DOL is a valid means of choosing patients to undergo OPCS while at the same time avoiding aggressive surgery in other patients unsuited for primary cytoreductive surgery.

Intraperitoneal chemotherapy with taxanes for ovarian cancer with peritoneal dissemination

Paclitaxel and docetaxel are currently the two clinically available taxanes. The combination of a taxane and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer. Despite the high activity of these drugs in systemic chemotherapy, the majority of patients with advanced ovarian cancer will develop recurrent disease and ultimately decease of this disease. Therefore, more effective systemic chemotherapy regimens or alternative treatment modalities are warranted. Intraperitoneal chemotherapy is such an alternative treatment option. Pharmacokinetic studies on intraperitoneal administration of paclitaxel and docetaxel demonstrated very high locoregional drug concentrations and exposure. Their activity and response seem to be dose-dependent and hence higher efficacy with limited systemic toxicity is to be expected. Intraperitoneal chemotherapy may be combined intraoperatively with hyperthermia, which enhances tissue penetration and cytotoxic activity of many drugs. The data concerning thermal enhancement of taxanes are inconsistent, but at the high locoregional concentrations provided by intraperitoneal drug administration such a thermal enhancement seems to exist. Clinical studies have clearly demonstrated the feasibility and efficacy of intraperitoneal instillation chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of a phase III study demonstrated improved outcome with the addition of intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel has been performed in a single study, in which promising results were observed. Further clinical investigations with an adequate follow-up period are needed to confirm the promising initial results and to determine the exact efficacy of intraperitoneal chemotherapy with these drugs.

Diagnostic open laparoscopy in the management of advanced ovarian cancer

Objective. Optimal primary cytoreductive surgery (OPCS) plus adjuvant chemotherapy (AC) represents the standard management for patients with advanced ovarian cancer (AOC). Recently, some authors have suggested the use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in patients with unresectable AOC. This study has been started to evaluate the role of diagnostic open laparoscopy (DOL) in predicting who are the best candidates to OPCS. Methods. All patients newly diagnosed as affected by AOC were submitted to DOL in order to establish the possibility of OPCS considered as no residual tumor left after operation. Patients considered not susceptible of OPCS were submitted to three cycles of NACT, administered every 3 weeks (Carboplatin, targeted AUC = 6, plus paclitaxel 175 mg/mq), followed by IDS and adjuvant chemotherapy. Results. From January 2000 to March 2004, 87 patients with AOC underwent DOL. Fifty-three patients (61%) were judged operable and therefore submitted to primary cytoreductive surgery (Group A). Optimal debulking rate in this group of patients was 96%. Thirty-four patients were judged affected by disease not cytoriducible to absent residual tumor and therefore scheduled for NACT-IDS-AC (Group B). Twenty-five patients were judged with partial clinical response and were therefore scheduled for IDS and AC. Optimal debulking rate (no residual tumor ) in Group B patients was 80%. No major perioperative complications, due to laparoscopy, occurred. All Group B patients received the first cycle of chemotherapy the day after DOL. In 34 patients (39%), an explorative laparotomy was avoided. With a median follow-up of 22 months (range 2–49 months), the proportions surviving were 87% and 60% in Group A and Group B patients, respectively. Conclusion. DOL could be considered a valid diagnostic tool in evaluating the extent of disease in AOC. Our data suggest that the use of DOL leads to decrease the rate of primary cytoreductive surgery for AOC; on the other hand, a higher optimal debulking rate (no residual tumor) at primary surgery is achieved.

Drug sensitivity-related benefit of systematic lymphadenectomy during cytoreductive surgery in optimally debulked stages IIIc and IV ovarian cancer

Objective. The purpose of this study is to assess the survival experience following systematic lymphadenectomy (LNX) in conjunction with primary but optimal cytoreductive surgery in advanced epithelial ovarian cancer (OC) patients when followed by intensive chemotherapy Methods. This is a retrospective analysis of all women with OC who were treated in our institution between 1992 and 2000. A total of 98 patients with stages IIIc–IV of OC underwent primary cytoreductive surgery which was ‘optimal’ (<1 cm residual disease). All patients subsequently received postoperative platinum-containing chemotherapy. Group I, consisting of 51 patients underwent LNX; Group II, consisting of 47 patients did not undergo LNX. The percentage of patients failing to respond to chemotherapy in each group was similar. Each group had statistically equivalent age, stage, regimens of chemotherapy performed, and all other known prognostic factors. Results. No survival benefit could be seen in platinum-sensitive patients. However, in patients who failed to respond to chemotherapy, the 2-year progression-free survival (PFS) (42.8% vs. 14.3%) and overall survival (OS) (51.2% vs. 28.8%) was quite different. LNX significantly improved those of drug-resistant patients when optimal cytoreductive surgery was performed [ P = 0.008, risk ratio (rr) = 2.675, 95% confidence interval (CI) = 1.251–5.724]. Cox's proportional analysis shows that LNX was one of the three most significant covariate with the tumor grade and the number of postoperative residual lesions. Conclusions. The results show that LNX might be of benefit in patients who have optimal primary cytoreductive surgery and who do not respond to platinum-based chemotherapy.