Negative Second-look Laparotomy Research Articles

GYNECOLOGICAL MALIGNANCIES

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)

Results of Second-Look Laparotomy in Advanced Ovarian Cancer: One Single Center Experience

Objective. The goal of the study was to analyse the results of 85 cases of second-look laparotomy (SLL) and explore the influence of this procedure on survival. Patients and Methods. We reviewed retrospectively 85 cases of SLL collected and treated in our institute between 1994 and 2003. Results. Complete pathologic response (CPR) was 25.8%, microscopic disease (Rmicro) was 38.8%, and macroscopic disease (Rmacro) was 35.4%. In patients with negative SLL results, disease recurrence was diagnosed in 41%. The 3- and 5-year overall survival rates for the entire population were 91% and 87%, respectively. The 3- and 5-year disease-free survivals were, respectively, 76.3% and 58.5% in negative SLL versus 55.7% and 16% in positive SLL. The difference between the group of patients with complete response (76%) and the patients with residual microscopic disease (72%) was not significant. The tumoral residuum after initial surgery was the only prognostic factor influencing significantly the disease-free survival. On Cox regression model analysis, only initial tumoral residuum (P = 0.04) and tumoral residuum after SLL (P = 0.02) were independent prognostic factors for survival. Conclusions. The most important advantage of SLL is the early detection of recurrence and thus the early administration of consolidation treatment resulting in a better prognosis.

Negative laparoscopy is highly predictive of negative second-look laparotomy following chemotherapy for ovarian, tubal, and primary peritoneal carcinoma

Negative laparoscopy is highly predictive of negative second-look laparotomy following chemotherapy for ovarian, tubal, and primary peritoneal carcinoma

Predictors and outcomes of recurrent disease after a negative second look laparotomy

To analyze the predictors and outcomes of recurrent disease in patients with epithelial ovarian carcinoma (EOC) after a negative second look laparotomy (SLL). One hundred nine EOC patients with a negative SLL treated at Hacettepe Hospital were retrospectively analyzed. Of these patients, 70 (64.2%) had no evidence of disease during follow up while remaining 39 (35.8%) had recurrence. Majority of the recurrences (82.1%) were detected within the initial 2 years of the SLL procedure. Multivariate analysis revealed stage and grade of the disease to be the significant predictors for the recurrent disease (P < 0.01 and P = 0.025, respectively). A second analysis with respect to initial metastatic sites revealed omental metastatis was significantly associated with recurrent disease (P < 0.001). Survival of patients with a recurrent disease was significantly poorer and dropped abruptly once a recurrence is developed. Patients with initial omental metastasis, advanced stage and high grade tumors have highest risk for developing recurrences after a (-) SLL. Most of the recurrences develop during the initial 2 years following the (-) SLL and survival drops to less than 2 years once a recurrence is found.

Negative laparoscopy is highly predictive of negative second-look laparotomy following chemotherapy for ovarian, tubal, and primary peritoneal carcinoma

Objective. To determine the negative predictive value of second-look laparoscopy compared to laparotomy for assessment of pathologic complete response (CR) in patients with epithelial ovarian, tubal, and peritoneal carcinoma who achieved a clinical CR. Methods. Data were analyzed from patients who participated in two sequential phase II clinical trials following primary cytoreductive surgery. Both trials required surgical evaluation for pathologic CR in those patients who achieved clinical CR. Protocol specified that assessment begin with laparoscopy; if negative, conversion to laparotomy was required. Collection of peritoneal washings was performed laparoscopically. Results. One hundred thirty-six patients entered the 2 sequential clinical trials. Ninety-nine patients achieved clinical CR and 95 underwent second-look surgery (SLO). Seventy patients began SLO with laparoscopy and converted to planned laparotomy after biopsies were negative. Eighteen cases were positive based on laparoscopy with frozen section. Five additional patients had peritoneal washings and/or permanent pathology positive based on laparoscopic findings, yielding a positive SLO rate of 32.9%. Four of the 52 patients who underwent laparotomy (7.7%) were found to have persistent disease that was not detected on laparoscopic biopsy or washings and represent false-negative laparoscopy; all four patients had disease at peritoneal-based sites. The sensitivity and negative predictive value for intraoperative diagnosis of persistent disease by laparoscopy were 66.6% and 82.7%, respectively. The sensitivity and negative predictive value of laparoscopic peritoneal biopsies and washings compared to laparotomy, as determined by final pathology, were 85.2% and 91.5%, respectively. Conclusion. A negative second-look laparoscopy with negative peritoneal pathology and cytology is 91.5% predictive of negative laparotomy and is associated with a low complication rate even in the setting of prior extensive cytoreductive surgery. The small increase in sensitivity and negative predictive value afforded by laparotomy does not warrant the increased morbidity.

Correlation of serum and ascitic IL-12 levels with second-look laparotomy results and disease progression in advanced epithelial ovarian cancer patients

Forty-two consecutive patients with advanced epithelial ovarian cancer who underwent primary surgical treatment were evaluated. The control group comprised 21 patients who had undergone surgery associated with benign pathologies. Forty-one patients had stage III disease except one who had stage IV. Optimal debulking (<1 cm) was performed in all the patients who subsequently received chemotherapy. Based on the results of the second-look laparotomy and follow-up, the patients were divided into three groups: the first group had negative second-look laparotomy or no evidence of disease during follow-up (n= 21), the second group had positive second-look laparotomy or progressive disease (n= 21), and the third was the control group (n= 21). Interleukin-12 (IL-12) levels were measured in preoperative serum and intraoperative ascites samples for all the patients. The mean serum IL-12 levels (+/-SD) in serum (S) and ascites (A) were as follows: in the first group, S: 108.44 +/- 76.40 pg/mL and A: 330.93 +/- 125.25 pg/mL; in the second group, S: 51.80 +/- 40.95 pg/mL and A: 206.89 +/- 113.47 pg/mL; and in the control group, S: 36.55 +/- 33.16 pg/mL and A: 93.62 +/- 73.07 pg/mL (P= 0.01). In the patients with advanced ovarian cancer, IL-12 levels in serum and ascites were higher compared to the levels of the controls. Also, there was an inverse relationship between initial serum and ascitic IL-12 levels and disease progression.

A 10-year review of primary fallopian tube cancer at a community hospital: a high association of synchronous and metachronous cancers

Primary fallopian tube carcinomas (PFTC) are rare gynecological tumors infrequently diagnosed prior to operative intervention. A retrospective review was performed to characterize the distribution and clinicopathologic significance of these tumors. Identification of PFTC was achieved through a review of the tumor registry and medical record ICD-9 codes at a community teaching hospital. A total of 1.5% of all gynecological cancers were PFTC. Most patients were presumed to have ovarian cancer. Ultrasound had the highest sensitivity (82%) for preoperative diagnosis. Surgical exploration was needed for definitive diagnosis in all patients. Optimal debulking was predictive of survival and of a negative second-look laparotomy (P < 0.05). Twenty-five percent of patients had a metachronous cancer diagnosed prior to their fallopian tube cancer, and 22% had a synchronous gynecological malignancy diagnosed at the time of surgical exploration. The response rate to platinum-based chemotherapy was 78%. The 5-year survival rate was 87%, and the overall survival rate was 75%. The median follow-up was 38 months. This report details the diagnostic and therapeutic experience of patients with PFTC and describes the occurrence of synchronous and metachronous gynecological cancers.

Efficacy of intraperitoneal continuous hyperthermic chemotherapy as consolidation therapy in patients with advanced epithelial ovarian cancer: A long-term follow-up

This trial was performed to determine the efficacy and progression-free and overall survivals of patients with advanced ovarian cancer who had been treated with intraperitoneal hyperthermic chemotherapy (IPHC). Ten patients with advanced ovarian cancer participated in this trial and were treated with IPHC. The median progression-free and overall survival rates for all patients treated in this study were 41.2 and 70.2 months, respectively. Two of ten patients received optimal primary cytoreduction surgery followed by IPHC; four of ten, optimal interval debulking surgery followed by IPHC; and four of ten, negative second-look operation followed by IPHC. The groups had 5 and 14.5, 17.75 and 38, and 82.75 and 130.25 months median progression-free and overall survival rates, respectively. Grades 3-4 toxicity included myelosuppresion, and nephropathy was detected. One patient required blood transfusions due to grade 4 anemia and thrombocytopenia. Another patient developed grade 3 nephrotoxicity but did not require continuous hemodialysis. IPHC was feasible, produced manageable toxicity, and showed promise for the treatment of advanced ovarian cancer. Negative second-look laparotomy followed by IPHC was especially effective when consolidation intraperitoneal chemotherapy had been indicated. It produced excellent median progression-free and overall survival rates.

Whole-abdomen, single-dose consolidation radiotherapy in patients with pathologically confirmed complete remission of advanced ovarian epithelial carcinoma: a long-term survival analysis.

The value of consolidation therapy in advanced epithelial ovarian carcinoma patients is controversial. The aim of the present study was to assess the long-term survival of patients with a pathologically confirmed complete remission who had consolidation by single-dose, whole-abdominopelvic radiotherapy. Of 96 histologically confirmed stage II-IV epithelial ovarian carcinoma patients who underwent cytoreductive surgery followed by high-dose, platin-based chemotherapy, 57 were in complete clinical remission at the end of therapy and 50 underwent a second-look laparotomy. The study group comprises 32 consecutive patients who had no pathological evidence of disease and who received 800 cGy single-dose, whole-abdominal radiotherapy by an 8 MEV linear accelerator in a single fraction. The absolute 5-year survival and the actuarial 10-year survival were 78.7 and 63.3%, respectively. The survival was significantly better in patients who had < or =2 cm residual disease at the completion of the original operation. No severe postradiation complications were encountered. Mild complications were seen in three (9.4%) patients. Our data indicate a favorable long-term survival of patients with a negative second-look laparotomy who had consolidation with single-dose, whole-abdominal radiotherapy. These results seem to suggest that a collaborative, prospective, randomized multiarm study is indicated to solve the controversial issue of consolidation therapy.

Whole-abdomen, single-dose consolidation radiotherapy in patients with pathologically confirmed complete remission of advanced ovarian epithelial carcinoma: a long-term survival analysis

The value of consolidation therapy in advanced epithelial ovarian carcinoma patients is controversial. The aim of the present study was to assess the long-term survival of patients with a pathologically confirmed complete remission who had consolidation by single-dose, whole-abdominopelvic radiotherapy. Of 96 histologically confirmed stage II–IV epithelial ovarian carcinoma patients who underwent cytoreductive surgery followed by high-dose, platin-based chemotherapy, 57 were in complete clinical remission at the end of therapy and 50 underwent a second-look laparotomy. The study group comprises 32 consecutive patients who had no pathological evidence of disease and who received 800 cGy single-dose, whole-abdominal radiotherapy by an 8 MEV linear accelerator in a single fraction. The absolute 5-year survival and the actuarial 10-year survival were 78.7 and 63.3%, respectively. The survival was significantly better in patients who had ≤2 cm residual disease at the completion of the original operation. No severe postradiation complications were encountered. Mild complications were seen in three (9.4%) patients. Our data indicate a favorable long-term survival of patients with a negative second-look laparotomy who had consolidation with single-dose, whole-abdominal radiotherapy. These results seem to suggest that a collaborative, prospective, randomized multiarm study is indicated to solve the controversial issue of consolidation therapy.

Laparotomía de second looken el tratamiento del áncer epitelial de ovario

Objective:To carry out a retrospective study on patients with ovarian epithelial cancer (OEC), diagnose in our Health Area (Cabuenes, Gijón) from 1991 to 2001.Material and methods:We review the patient’s characteristics, tumor and treatment carried out, with the intention of establishing the role of second look laparotomy (SLL) in the treatment of OEC, and its possible impact on patients survival.Results:During the period studied SLL was carried out on 70 patients who, following primary treatment with surgery and chemotherapy were apparently free f disease. Although the women with negative SLL had better survival rates than women with residual disease, no statistically significant differences in global survival or post-SLL were found, even when there was residual disease following this surgery. On completion of treatment, we found recurrence in 41% of patients had been disease free, a level very similar to the 39% found in the patients with negative SLL, which demonstrates the high index of false negatives in this type of surgery.

Long-term survival with consolidation intraperitoneal chemotherapy for patients with advanced ovarian cancer with pathological complete remission

Objective The goal of this study was to evaluate the long-term outcome after consolidation intraperitoneal (IP) chemotherapy in patients with a negative second-look laparotomy (SLL) following first-line intravenous chemotherapy for advanced ovarian cancer. Methods This study included patients with FIGO stage III–IV ovarian cancer who entered into four prospective trials (1984–1995) including intravenous chemotherapy based on cisplatin (six cycles) and anthracycline, early debulking surgery after three cycles of chemotherapy in the case of initial residual disease >2 cm, SLL, and IP consolidation chemotherapy. Among 218 patients, 68 with biopsy-negative SLL received every 4 weeks three consolidation cycles of IP chemotherapy (mitoxantrone, cisplatin, etoposide) via a totally implantable port. Long-term outcome of these patients is reported. Results Mean age was 56 years (33–72 years). Overall, 51% of the patients had at least a grade 3 or 4 toxic effect. Main toxic effects were leukopenia, abdominal pain related to the catheter, and nausea and vomiting. Only 13 patients (19%) did not receive the full three cycles. The median progression-free survival (PFS) for the whole population is 34 months, 34% of the patients being estimated to be free of disease at 5 years. The median overall survival is 73 months, and the 5-year survival is 58%. Conclusion In this selected population treated with IP consolidation chemotherapy, prolonged survival was observed. However, the occurrence of late relapses in this most favorable patient category underlines the need to improve the consolidation therapy options in ovarian cancer.

Prognostic significance of second-look laparotomy for surgically confirmed early-stage epithelial ovarian cancer: a multicenter retrospective study

In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic significance of second-look laparotomy (SLL) in early-stage epithelial ovarian cancer that was confirmed by complete surgical exploration. In July 2001, 12 Japanese institutions received questionnaires regarding patients with early-stage epithelial ovarian cancer and SLL. Eligibility criteria included patients with stage I or II epithelial ovarian cancer who were surgically diagnosed between January 1988 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, stage, preoperative carbohydrate antigen (CA) 125 level, results of SLL if performed, recurrence, disease-free survival, and overall survival. Survival analyses and comparisons were performed by univariate methods. There were 87 patients who met the eligibility criteria. There were no significant differences in the backgrounds of patients who had had SLL ( n = 30) and the non-SLL group ( n = 57). Of the 30 SLL-group patients, 28 had negative SLL findings and 2 had positive findings. Six and 5 patients in the SLL group and the non-SLL group, respectively, had recurrence ( P = 0.177), and 4 patients in the SLL group had a recurrence after "negative" SLL findings. There was no significant difference between the two groups for either overall ( P = 0.73) or disease-free survival ( P = 0.273). On univariate analysis, only clear-cell histology was associated with a poor prognosis in early-stage epithelial ovarian cancer ( P = 0.031). SLL is not beneficial for early-stage epithelial ovarian cancer. More favorable outcomes will be achieved for early-stage patients with the improvement of treatment for clear-cell adenocarcinoma.

Randomized trial of intraperitoneal chronic phosphate therapy versus observation following negative second-look laparotomy for stage III ovarian carcinoma: a gynecologic oncology group study

Purpose/Objective: The objective of this trial was to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal chromic phosphate suspension (ip 32P) therapy in patients with Stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure.

Impact of second look laparotomy and secondary cytoreductive surgery at second-look laparotomy in ovarian cancer patients

Currently, no prospective study supports or refutes the value of secondary cytoreductive surgery in patients with ovarian cancer. We therefore reviewed the surgical data of patients who underwent second-look laparotomy (SLL) with or without secondary cytoreductive surgery at our department. Analysis is based on the data of 179 patients who had FIGO stage II (suboptimally staged), stage III or IV ovarian cancer, who received a platinum-based first-line chemotherapy, who were clinically considered to be tumor-free or had at least a clinically partial response to first-line chemotherapy, and who underwent SLL. In patients with macroscopic tumor the diagnostic SLL was followed by a secondary cytoreductive surgery in order to remove as much tumor as possible. Patients with a positive SLL were given second-line chemotherapy. Survival from SLL until death was considered the primary statistical endpoint. In 78 out of 179 (43.5%) a negative SLL could be confirmed pathologically. Patients with negative findings, with microscopic, and macroscopic disease at SLL had a median survival of 66.6, 57.2, and 19.0 months, respectively (p=0.0001). In patients who underwent a secondary cytoreductive operation and in whom residual tumor was none, less than 2 cm, or more than 2 cm, the median survival was 22.9, 17.8, and 15.5 months, respectively (p=0.325). The presence of macroscopic tumor at SLL is an adverse prognostic factor whereas the role of secondary cytoreductive surgery at SLL appears to be limited in the routine management of ovarian cancer patients.

Treatment of fallopian tube cancer. Review of the literature.

To contribute toward the understanding of the therapeutic management of fallopian tube cancer. Recent studies related to the treatment of fallopian tube cancer were reviewed. Current evidence indicates that even patients in early stages have nodal disease, and often experience relapses in distant sites. In advanced stages, survival prolongation by the use of platinum-based chemotherapy has been demonstrated. Aggressive cytoreductive surgery followed by chemotherapy and negative second-look laparotomy offer the possibility of long-term survival. However, a significant fraction of patients eventually relapses after negative second-look laparotomy, and a poor survival rate after positive second-look laparotomy has been observed. This series suggests the need for thorough evaluation of lymph nodes at the time of surgery. The use of platinum-based chemotherapy is probably the best adjuvant therapy for both early stages and advanced stages. The clinical value of second-look laparotomy will remain limited until effective salvage therapy is developed. The potential benefits of neoadjuvant chemotherapy and the use of paclitaxel will be increasingly important.

Results of second-look laparotomy with extensive dissection of retroperitoneal lymph node in ovarian cancer patients

Objective: To evaluate retrospectively the results of extensive lymphadenectomy during second-look laparotomy on patients with ovarian cancer. Methods: A total of 63 patients with ovarian malignancies received second-look laparotomy (SLL). Retroperitoneal lymph nodes, including pelvic and para-aortic lymph nodes below the level of left renal vein, were extensively dissected. Results: Of the 63 patients, residual tumor was found in 24 (38.0%) on SLL. The frequency of residual tumor was positively correlated with the clinical stage and with the amount of tumor left after initial debulking but not with degree of differentiation of tumor cells. Lymph node metastasis(LNM) was pathologically confirmed in 19 cases (30.2%), of which no residual tumor was found in 8 patients. Tumor recurred in only 4 of the 39 patients (10.3%) with negative SLL. The overall 3- and 5-year survival rate were 75.0% and 68.0%, respectively. Conclusion: Extensive retroperitoneal lymph node dissection was recommended during SLL. It favored a decrease in recurrence rate in ovarian cancer patients negative on SLL.

Second-look and second surgery: second chance or second best?

About 40 years ago, second-look laparotomy (SLL) was introduced to evaluate, surgically and pathologically, primary treatment in case a clinical complete remission was obtained in ovarian cancer patients. But does SLL increase the disease-free or overall survival? Important technical aspects of the procedure as: how many biopsies should be taken, can laparoscopy be replaced by laparotomy and should complete lymphadnectomy be performed at SLL, are still not clarified. This and maybe even more important issues, are disputed in literature: for instance, should a SLL be done at all, or should a SLL be performed in order to do a secondary cytoreduction in case tumour is found at the operation. If clinical remission is reached in more than 50% of the patients with advanced disease, tumour still can be found at SLL. If no tumour is found at SLL, macroscopically or microscopically, the operation is redundant. Apart from this, the recurrence rate after such a "negative SLL" is about 35%. Whether tumour found at SLL should be removed will depend on the fact if the tumour still is responsive to chemotherapy. To minimise the chance of tumour resistance, secondary surgery should be done as early as possible during treatment. Therefore, an interval debulking will be the intervention of choice. So, as long as there is no evidence that SLL increases the survival in ovarian cancer patients, it should be done in a research setting only. Also, the usefulness of secondary surgery for recurrent disease mainly depends on the chemo-sensitivity of the tumour. After a complete remission, which lasts for more than a year, complete secondary cytoreduction, again followed by chemotherapy, improves survival.

Simplified Laparoscopic Approach to “Second-Look” Laparotomy: A Review

Acute mesenteric vascular accidents are being diagnosed more commonly as a consequence of an aging population and often result in emergency bowel resection for ischemia. Because predicting postoperative intestinal viability remains difficult, second-look laparotomy has been advocated to improve outcomes. Recently, laparoscopy has emerged as an alternative to laparotomy for the diagnosis and treatment of ongoing postoperative ischemia. A review of the literature since 1994 reveals that, to date, 19 procedures have been reported to prevent 13 (68%) unnecessary laparotomies. We describe our laparoscopic second- look technique and review the literature. Second-look laparoscopy has been shown repeatedly to be a safe alternative to laparotomy. It is simple and reduces negative second-look laparotomy in critically ill patients.

Clinical Significance of Apoptosis-Related Factors p53, Mdm2, and Bcl-2 in Advanced Ovarian Cancer

To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer. Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined. Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival. p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.