A review of second-look laparotomy for ovarian cancer

One hundred twenty-seven patients underwent second-look laparotomies from July 1969 to June 1982. To be included in this report they must have met the following criteria: a documented ovarian neoplasm; previous surgery; adequate chemotherapy for cessation if no disease was found; and no X-ray, chemical, or clinical evidence of disease including an exam under anesthesia. Forty-one percent had residual disease at second-look laparotomy. The original stage and the percentage of tumor debulked at initial surgery were inversely related to the likelihood of finding residual disease. Age, histologic type and grade, and type of chemotherapy did not show a significant relationship with the likelihood of disease persisting. Recurrent tumor was subsequently detected in 16% of patients who had been found to be free of disease at second-look laparotomy. Of thirty stage III and IV patients treated with combinations containing cis-platinum, 10 (33%) had recurrences. This rate of recurrence was significantly greater than the 17.6% recurrence rate in 17 patients with Stage III and IV disease whose chemotherapy consisted of single alkylating agents or with combinations without cis-platinum. Twenty patients underwent a third-look laparotomy after completion of additional chemotherapy. Nine were found to have no residual disease. Two of the nine (22%) subsequently had recurrence of disease. Three of the eleven patients with persistent disease at the time of a third-look laparotomy underwent a fourth-look laparotomy. All were found free of disease and none have recurred. Six (55%) of those with persistent disease at the third-look laparotomy have died despite continued therapy. The ability to successfully treat some patients with persistent disease continues to be a justification for the use of a second-look laparotomy. However, the high rate of recurrence after cessation of treatment following the finding of no residual disease raises the question of whether it is appropriate to discontinue all therapy at this time.     

The significance of müllerian inclusions found at second-look laparotomy in patients with epithelial ovarian neoplasms

When no visible tumor is identified at second-look laparotomy, selected biopsy specimens or cytologic washings may reveal microscopic tumor or benign pathologic atypia. The pathology material from 311 patients with epithelial ovarian carcinoma who had no macroscopic tumor at second-look laparotomy was evaluated for psammoma bodies, müllerian inclusions (benign glandular inclusions), microscopic tumor, and either inflammation or fibrosis. Progression-free intervals and survival rates were influenced by the presence of müllerian inclusions (favorably), tumor or positive cytology (unfavorably), and inflammation or fibrosis (unfavorably). Multivariate analysis (proportional hazards model) demonstrated that both the progression-free interval and survival rates were influenced significantly by the presence of microscopic tumor and tumor grade. Of 51 patients with müllerian inclusions and no microscopic tumor, 23 received additional treatment after second-look laparotomy. No differences were noted in the progression-free interval or survival rates when these patients were compared with the 28 nontreated patients. Of the treated patients, three died from chemotherapy toxicity, whereas there were no chemotherapy-related deaths in the nontreated group. These findings indicate that the presence of müllerian inclusions at second-look laparotomy does not justify treatment, and that further treatment after misinterpretation of these benign pathologic entities may lead to harmful results.     

Platinum-Based Chemotherapy for Advanced-Stage Serous Ovarian Carcinoma of Low Malignant Potential

Purpose: To evaluate the effect of platinum-based chemotherapy on tumor response in patients with advanced-stage serous ovarian carcinoma of low malignant potential. Patients and methods: We conducted a retrospective review of hospital records, pathology slides, and office charts of patients identified as having Stage III or IV serous ovarian cancer of low malignant potential. Results: Between November 1979 and April 1993, 21 patients with advanced-stage serous ovarian carcinoma of low malignant potential received platinum-based chemotherapy following initial cytoreductive surgery. The amount of residual disease was recorded in 20 patients; 8 (40%) had macroscopic residual tumor <2 cm in largest diameter, and 12 (60%) had only microscopic disease. Sixteen patients underwent a second-look laparotomy following chemotherapy; 10 (62.5%) had no evidence of disease, 1 (6%) had a partial response, 2 (12.5%) had stable disease, and 3 (19%) had progressive disease. During a mean follow-up of 64 months, only 1 patient had died of disease. She had progressive disease noted at second-look laparotomy. Five of 6 patients who did not have a complete response to initial chemotherapy underwent further therapy with oral etoposide (1), intraperitoneal platinum (2), intraperitoneal mitoxantrone (1), or both (1). The sixth patient received no further therapy. Three of the patients subsequently receiving salvage intraperitoneal therapy underwent a third-look laparotomy. Two had partial responses noted, while the third patient had stable disease. Conclusions: Platinum-based chemotherapy is effective in achieving surgically documented responses in patients with advanced-stage serous ovarian tumors of low malignant potential. The benefit of this therapy in improving survival is unproven.     

Survival of patients with ovarian epithelial carcinomas after second-look laparotomy

Survival of ovarian carcinoma patients undergoing second-look laparotomy after primary surgery and adjunctive chemotherapy was evaluated by retrospective chart review. From August 1976 to August 1987, 102 patients with stage I-IV disease underwent second-look laparotomy. Optimal tumor debulking and early (stage I or II) disease were positively correlated with a negative second-look laparotomy. Of the 49 patients with a "negative" second look, 15 demonstrated recurrent tumor from 12.5 to 52.5 months after laparotomy. Of the 15 recurrences, 6 were documented more than 3 years following second look. Half of the 28 patients with stage III disease and a "negative" second look have demonstrated recurrent tumor. Fifty-three patients (52%) were found to have residual disease at second-look laparotomy. Initial chemotherapy (melphalan or multiple agent) and the adequacy of primary debulking surgery (optimal vs suboptimal) were not significant factors contributing to patient survival after a positive second look. However, the size of residual disease at second-look laparotomy was a significant factor in subsequent patient survival (P less than or equal to 0.01). Fifteen patients were free of gross disease at laparotomy, but had residual tumor on microscopic examination of the specimens submitted. These patients had a 2-year actuarial survival of 78%. Forty-seven percent have survived 5 or more years after second look. Nineteen patients with tumor implants 2 cm or smaller had 2- and 5-year actuarial survivals of 61 and 31%, respectively. Nineteen patients with tumor nodules larger than 2 cm in diameter had a 2-year actuarial survival of 6%. Only 1 of 19 patients with nodules greater than 2 cm could be effectively redebulked.     

The value of second-look operation in patients with advanced epithelial ovarian carcinoma

Summary A second-look operation was performed on 151 patients with stage III and IV epithelial ovarian carcinoma who had responded to primary surgery and chemotherapy. 19% of the 79 patients who appeared clinically to be free of disease had microscopic recurrences and 23% had macroscopic residual disease at a second-look operation. The 5-year survival rate for patients with no histological and for those with microscopic secondaries at second-look operation were 55% and 35% respectively (P=0.45). Only patients with well or moderately well differentiated tumors and a small residual tumor mass at first operation had a good prognosis after a second-look operation even without further chemotherapy. Median survival after secondary debulking was 15 to 17 months and was independent in the radicality of the second-look procedure. Outside of clinical trials second-look laparotomy should therefore only be performed as a diagnostic procedured as a diagnostic procedure in patients with well or moderately well differentiated tumors who are left with a small residual tumor mass at the time of the first operation. Because this is a group of patients in whom chemotherapy can be discontinued after a negative second-look operation.     

Use of CA 125 to monitor patients with ovarian epithelial carcinomas

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.     

Place of Second-look Laparotomy After 18 Courses of Chemotherapy in Epithelial Ovarian Cancer

Summary: Thirty-two patients with epithelial carcinoma of the ovary underwent a second-look laparotomy after the completion of an average of 18 courses of adjuvant chemotherapy. Nine patients (28%) were found to have persistent disease. This low-rate of positive second-look laparotomy is probably because these patients received chemotherapy for 18 months and in those patients whose tumour did not respond to the medication, the disease would progress and the patient died without becoming a candidate for laparotomy.
There was no stage 1c patient whose second-look laparotomy was positive and the need for second-look laparotomy is questionable in such patients. Stage 111/ IV patients and patients with recurrence had a significantly higher positive second-look laparotomy rate than stage Ic/II patients, 44% and 7% respectively. In the present group of patients with positive tumour at second-look laparotomy, 33% responded to further debulking operation and chemotherapy and remained disease free 15–33 months after completion of their second line chemotherapy treatment. For second-look laparotomy to be of maximum benefit to the patient, we recommend that it be performed after 12 courses of chemotherapy.     

Use of second-look laparotomy in the management of patients with ovarian epithelial malignancies

Between June 1976 and January 1986, 94 evaluable patients with stage I-IV disease underwent second-look laparotomy as part of their treatment for ovarian epithelial carcinomas. Stage and residual tumor size after initial debulking surgery demonstrated a significant association with absence of disease at reexploration. Forty-nine patients (52%) had no evidence of disease at second-look laparotomy. Thirty patients (32%) had macroscopic residual tumor, and 15 patients (16%) had microscopic disease at reexploration. Patients with a negative second-look laparotomy had an excellent prognosis; uncorrected 2- and 5-year survival rates exceed 90%. None of the patients with stage I or II disease developed recurrent tumor after a negative second-look laparotomy. However, 7 of the 25 (28%) patients with stage III disease and a negative second-look have demonstrated recurrent carcinomas. Recurrences were documented from 15.4 to 51.7 months after second-look laparotomy and were located within the abdominal cavity. Life table methods demonstrated improved survival for patients with microscopic disease as compared to those with gross tumor at second-look survey. Both groups had similar mean patient ages and tumor stage distributions. Patients with microscopic residual disease had uncorrected 2- and 5-year survival rates of 76 and 64%. The 2-year uncorrected survival rate for patients with gross tumor at second-look laparotomy was 25%. Thirty patients with macroscopic disease at second-look laparotomy underwent a repeat attempt at tumor debulking. Seventeen patients completed second-look surgery with residual disease less than 1 cm in maximum dimensions. Life table methods demonstrated improved survival when residual disease was less than 1 cm. Regardless of residual tumor size after reexploration, patients with gross tumor had a worse survival than those with microscopic disease.     

The second-look celiotomy in ovarian cancer

Thirty-six patients with primary ovarian carcinoma who had 42 second-look procedures performed are reported. Twenty-three patients had no tumor found at the second-look celiotomy and were given no further treatment. Thirteen patients had tumor at the second-look procedure and were continued on therapy. Six patients have died with disease and all had a positive second-look celiotomy. Two patients have died with leukemia but with no evidence of ovarian cancer, one after a negative second-look and the other a negative third-look. No patient with a negative second-look celiotomy has died with disease. A correlation with respect to the findings at the second-look was found with respect to the stage of disease and the amount of residual tumor at the initial surgery. The use of the second-look celiotomy in patients with disease in the early stages and in patients treated with irradiation is discussed, along with the utilization of the laparoscopy.     

Chemotherapy versus radiotherapy in the management of ovarian cancer patients with pathological complete response or minimal residual disease at second look

The management of patients with epithelial ovarian cancer with no or minimal residual disease at second-look laparotomy after aggressive surgery and platinum-based chemotherapy has not been definitively established. We report the results of a randomized study comparing three more courses of the same chemotherapy inducing the response (21 patients) with whole-abdomen radiotherapy (20 patients). Thirty-eight patients responded to first-line chemotherapy and three had stabilization of disease. In eight patients tumor debulking was performed at second-look laparotomy. No severe toxic effects were noted in both arms. Bowel obstruction occurred in one patient treated with radiotherapy. At a median follow-up of 22 months, 11 of 20 patients in the radiotherapy arm and 6 of 21 in the chemotherapy arm progressed and 9 and 3 patients died, respectively. Although the number of randomized patients is small we stopped the trial because of the survival and progression-free survival advantage of chemotherapy-treated patients.     

Second-look procedures in ovarian cancer patients receiving six vs. nine courses of platinum, adriamycin, cytoxan (PAC) chemotherapy: the SCPMG experience 1982-1985

From July 1, 1982, through December 31, 1985, 100 patients with Stage I, II, or III ovarian cancer, who were clinically NED following primary chemotherapy, underwent second look laparotomy. A prospective, nonrandomized study was set up among the various institutions within the Southern California Kaiser Permanente Medical Group. Those patients being treated at the Tertiary Oncology center received six courses of PAC while patients treated at other centers received nine courses of PAC. There was no selection as to severity of disease. Patients with Stage IV disease were not subjected to second-look procedures. Twenty patients with Stage I disease received other than PAC chemotherapy. Eighty patients with Stage II and III disease received PAC chemotherapy; 39 had six courses and 41, nine courses or more of PAC. Standard second-look procedure was performed and the status of the second-look procedure was the determining factor of response. Eighteen of the 39 patients (46%) who received six courses and 26 of 41 patients (63%) who received nine courses of chemotherapy had negative second-look procedures. Sixty-five patients had Stage III ovarian cancer, 34 with six courses of therapy and 31 with nine courses of therapy. There was no statistical difference in the incidence of positive or negative second-look procedures between the groups. The therapeutic index of six courses of PAC chemotherapy was in our hands, higher than with nine courses, since there was no observed difference in the status of the second-look and there was significantly more toxicity with the nine courses of therapy.     

Adriamycin and cisplatin in the treatment of stage III and IV epithelial ovarian carcinoma

A total of 342 eligible, previously untreated patients with Stage III or IV epithelial ovarian carcinoma were treated with Adriamycin and cisplatin, both at 50 mg/m2, for nine courses. Of the 210 patients who had clinically detectable disease after initial surgery, 85 (41%) had a complete clinical response and 45 (21%) had a partial clinical response. A total of 197 were clinically free of disease at the completion of chemotherapy and 175 of these had a second-look laparotomy; 55 had no macroscopic or microscopic evidence of residual disease after multiple random biopsies were examined histologically (complete surgical/histologic response). The major determinants of complete surgical/histologic response were diameter of largest residual tumor prior to treatment, ECOG performance status, and grade, patients with grade 3 tumors having a higher complete response rate than those with grade 1 or 2 tumors. The major determinants of survival were ECOG performance status and diameter of largest residual tumor prior to treatment. Median survival of the total group was 1.8 years.     

The role of second-look laparotomy in the management of patients with stage II, III and IV ovarian cancers following chemotherapy with cisplatin, adriamycin and cyclophosphamide

Twenty-eight patients underwent a second-look laparotomy on completing triple agent chemotherapy with cisplatin, adriamycin and cyclophosphamide. The adequacy of the primary debulking procedure and the stage of tumour were the most significant factors associated with a good prognosis. Grade and histological type of tumour had no effect on survival rates. Eighteen patients were surgically free of disease at the second-look procedure and of these, all are alive and disease free with a mean survival time of 39 months. Of the 10 patients with positive second-look procedures, four are dead. The mean survival for patients with positive second look laparotomies was 30.7 months. Second-look laparotomy may contribute to increased survival if pelvic clearance was not attempted at initial staging laparotomy but should primarily be used to assess new agents and new combinations of chemotherapeutic agents and to define the optimum number of courses of chemotherapy.     

Second-look laparotomy in ovarian cancer: evaluation of pathologic variables

From 1977 through 1982, 135 patients with ovarian cancer, having a mean age of 53.7 years and no clinical evidence of disease after approximately 1 year of treatment, underwent a "second-look" laparotomy. Of the 135 patients, 58 (43%) had histologic confirmation of disease at the second-look procedure. Persistent disease was positively correlated with the original stage and negatively correlated with the extent of the original reductive surgery. The original histologic grade or cellular subtype did not significantly influence the findings at reexploration. Patient survival, as judged by percentage of patients alive 3 years after the second-look laparotomy, was dependent on the following surgical/pathologic parameters: tumor size at reexploration, peritoneal cytologic features, residual tumor after reexploration, and histologic grade.     

Second-look laparotomy in the management of epithelial ovarian carcinoma: an evaluation of fifty cases

Fifty patients with ovarian cancer had a second-look laparotomy performed after chemotherapy. Complete histologic response was confirmed in 12 patients, microscopic disease was found in 12 patients, and macroscopic disease was found in 26 patients. Fifteen patients with macroscopic disease had total tumor clearance at second look. Surgical response to chemotherapy was found to correlate well with disease volume at the onset of chemotherapy. The operation is a safe, accurate technique for assessing the ovarian cancer patient. The findings and outcome probably depend upon the timing of the procedure. Any survival benefit from the operation remains to be proved.     

Influence of secondary cytoreduction at the time of second-look laparotomy on the survival of patients with epithelial ovarian carcinoma

The value of secondary cytoreductive surgery at the time of second-look laparotomy in patients with epithelial ovarian carcinoma is not established. Sixty-seven patients with residual carcinoma found at the time of second-look laparotomy performed at Memorial Sloan-Kettering Cancer Center between December 1, 1978, and May 30, 1986, were evaluated for survival relative to the success of secondary cytoreductive surgery. At second-look laparotomy, 17 patients had microscopic disease, 28 patients had disease less than 2 cm and 22 patients had disease greater than 2 cm. After secondary cytoreductive surgery 33 patients had microscopic disease, 26 patients had disease less than 2 cm, and 7 patients had disease greater than 2 cm (1 unknown). Five-year survival by Kaplan-Meier calculation was 62% for patients found to have microscopic disease at second-look laparotomy and 51% for patients whose disease was rendered microscopic by secondary cytoreductive surgery (P = 0.55). Patients left with gross disease (either less than or greater than 2 cm) had 5-year survivals of less than 10% (P = 0.013 compared with microscopic residual). Secondary cytoreductive surgery at the time of second-look laparotomy in patients with epithelial ovarian carcinoma may result in improved survival of patients who are reduced to microscopic residual disease.     

Second-look laparotomy in the management of malignant germ cell tumors of the ovary

From 1970 to 1985, 53 patients with malignant nondysgerminomatous germ cell tumors of the ovary underwent second-look laparotomy after initial surgery and combination chemotherapy. Twenty-two patients had immature teratoma, 15 had endodermal sinus tumor, 15 had mixed germ cell tumor, and one patient had embryonal carcinoma. Thirty-one of the neoplasms were stage I, four were stage II, 17 were stage III, and one was stage IV. Two patients received a combination of actinomycin-D, 5-fluorouracil, and cyclophosphamide; four patients received vinblastine, bleomycin, and cisplatin; 44 patients received vincristine, actinomycin-D, and cyclophosphamide; and three patients received a combination of the last two regimens. Second-look findings were negative in 52 patients and positive in one patient who was subsequently salvaged with further chemotherapy. One patient with stage I endodermal sinus tumor relapsed nine months after a negative second-look laparotomy and died. Two patients with negative findings subsequently died of leukemia. Of 53 patients undergoing second-look laparotomy, three are dead (one of cancer and two of leukemia), and 50 patients are surviving without disease. Although the precise role of second-look laparotomy in patients with malignant germ cell tumors is yet to be established, possible indications are discussed.     

Survival of ovarian carcinoma with or without lymph node metastasis

Because of the limited number of reports concerning the influence of retroperitoneal lymph node metastasis upon survival in patients with ovarian carcinoma, a prospective study was conducted between December 1975 and December 1982 to provide such information. This series consisted of 75 unselected patients with epithelial carcinoma of the ovary in all stages. Thirty-three patients had tumor-positive nodes and 42 had negative nodes. The two groups were compared with regard to stage of disease, grade of tumor, histology of tumor, residual disease after initial operation, finding at second-look laparotomy, and survival. All had initial maximal surgery and biopsy of para-aortic and pelvic nodes: most received postoperative chemotherapy. Follow-up was from 36 months to 10 years. Patients with positive nodes preferentially had more advanced disease (Stage III and IV). Grade 3 tumor, papillary serous cystadenocarcinoma, residual disease greater than 2%, low rate of second-look laparotomy, and death. Patients with negative nodes were connected with earlier disease (Stage I and II), nonserous tumor, minimal residual disease, high rate of second-look laparotomy, and survival. No patient with isolated nodal metastasis to pelvic or para-aortic survived. Only 18.2% with concomitant para-aortic and pelvic node involvements are currently alive, opposed to 64.3% with negative node. The results indicate that tumor-positive nodes in ovarian carcinoma are a poor prognostic factor and current combination chemotherapy is not effective. Alternative treatment for these patients should be considered.     

Second-look laparotomy in epithelial ovarian cancer: an evaluation of 23 cases

Between 1981-1988, 23 patients with epithelial ovarian cancer underwent second-look laparotomy after initial surgery followed by multiple courses of chemotherapy. There was no evidence of tumor before operation. Six patients (26%) had gross tumor and 5 (22%) had microscopic tumor. One of 3 patients with stage I or II and 50% (10/20) of patients with stage III and recurrent disease had positive second-look. Two of 7 (29%) patients with no residual tumor after initial surgery and 9 of 16 (56%) with residual tumor had positive second-look. It showed that the results of second-look were correlated with stage and residual tumor left after initial surgery. Sixteen patients had CA125 serum immunoassay prior to second-look. CA125 level was in normal limits (less than or equal to 65 U/ml) in 12 patients. Positive second-look findings were observed in 7 patients (58%), of which 5 had microscopic tumors. The results indicate that the second-look laparotomy is probably the best way to evaluate residual tumor in the abdominal cavity.     

Stage I ovarian epithelial carcinoma: survival analysis following definitive treatment.

Between 1977 and 1986, 55 patients with surgical stage I ovarian epithelial carcinoma were managed in a definitive fashion, which included surgical staging and adjuvant therapy in 51 of 55 patients (93%) and second-look laparotomy. The mean follow-up time from the data of reassessment surgery was 94 months, allowing sufficient time to facilitate the identification of one or more subgroups of patients at risk of having persistent disease or developing a recurrence. Treatment failures were detected at second-look laparotomy in 6 patients (11%), and an additional 5 patients (9%) subsequently had recurrences after being declared free of disease at second-look reassessment. Analysis of pathologic variables identified grade and substage as important prognostic factors, with 8 of the 9 deaths (89%) being associated with Broders grade 3 or 4 and/or stage IC. Within the bivariate model consisting of patients harboring poorly differentiated (grade 3 or 4) stage IC lesions, 6 of 14 patients (43%) are dead from disease, yielding a long-term survival rate that at best approximates the survival rate associated with optimally reduced (microscopic residual) stage III patients subjected to contemporary adjuvant therapy and reassessment surgery. These data suggest that intensive therapy as utilized in advanced disease, including platinum-based chemotherapy, second-look laparotomy, and innovative salvage or investigational consolidation therapy, is equally applicable to this "high-risk" stage I group.