Second-look laparotomy in epithelial ovarian carcinoma. Prognostic factors associated with survival duration

This article that reports on 70 consecutive patients is one of only a few studies of advanced ovarian cancer that have attempted to define predictive factors associated with survival duration after second-look laparotomy. As in many other investigations, several factors have been analyzed for predicting second-look outcome. The prognostic variables analyzed in this study included age, stage, histologic grade, residual disease status after initial surgery, and type (cisplatin versus no cisplatin) and number of cycles of chemotherapy. Only stage (P = 0.002) and optimal disease (less than 2 cm residual tumor size) after initial surgery (P less than 0.001) were significantly associated with the absence of disease at second-look laparotomy, and both were significant predictors of second-look outcome in a multivariate logistic regression model. Their impact on actuarial survival after second-look laparotomy diminished, however. Actuarial survival after second-look laparotomy was associated with residual tumor size at second-look surgery (P = 0.02). According to second-look findings, the 3-year actuarial survival rates and standard errors were as follows: no pathologic evidence of disease, 80.7% +/- 13.4% 3-year survival; microscopic disease plus less than or equal to 2 cm residual disease, 49.1% +/- 13.1% survival; and gross residual disease (i.e., greater than 2 cm maximum tumor diameter), 29.5% +/- 11.4% survival. We also examined the effect of extensive tumor resection at second-look laparotomy on survival for patients with greater than 2 cm gross residual disease. Optimum resection (less than 2 cm residual tumor mass) resulted in significantly greater survival than suboptimum resection (P less than 0.001). This strongly suggests that there is a survival advantage associated with optimum resection at second-look laparotomy.     

Consolidation radiation therapy following cytoreductive surgery, chemotherapy and second-look laparotomy for epithelial ovarian carcinoma: long-term follow-up.

BACKGROUND: From 1979-1987, 139 stage IC-IV ovarian cancer patients who had undergone cytoreductive surgery received 6-11 cycles of cisplatin and adriamycin. STUDY DESIGN: Eighty-four clinically complete responders underwent second-look laparotomy, and 60 of them received consolidation abdominal irradiation. The patients were then followed for a median follow-up of 39 months. RESULTS: Five- and 10-year actuarial survival for all patients was 43% and 24%, for no residuum at primary surgery, 80% and 35%, for residual tumor <2 cm, 45% and 35%, and for residual tumor >2 cm, 20% and 4%. Median survival for stage III-IV patients negative at second-look laparotomy was 72 months in irradiated compared to 25 months in non-irradiated patients (P = 0.14) and 77 months in irradiated patients with microscopic disease at second-look laparotomy. Median survival in patients with macroscopic disease at second-look laparotomy was 23.5 months if irradiated compared to 18 months if not (P = 0.05). CONCLUSIONS: Consolidation whole abdominal irradiation in advanced stages of ovarian cancer may be of value in patients with negative or microscopic disease at second-look laparotomy. Unfortunately, despite the initial survival advantage observed in irradiated patients, owing to late recurrences there was no significant difference in their long-term survival probability.     

Evaluation of the second-look laparotomy in the management of carcinoma of the ovary

One hundred and thirty four patients had a second-look laparotomy in the course of management of cancer of the ovary. Patients were stratified according to four indications: (1) resection of the residual tumor following chemotherapy or radiation therapy, (2) evaluation of the disease with intent to stop chemotherapy and assess signs of recurrence or persistence, (3) restaging, and (4) surgical indication. The first group consisted of 35 patients. In 20 of 35 patients in this group, complete removal of the residual tumor (residual less than or equal to 2 cm) was possible, and the survival curves indicated that removal of the residual tumor during the second-look laparotomy improved the survival rate. The second group consisted of 77 patients. No evidence of disease was found in 44 of the 77 patients in this group. Four patients with negative second-look laparotomy developed recurrences, and three patients died from the disease. The third group consisted of seven patients. In one of seven patients in this group, the stage was modified after second-look laparotomy.     

Abdominopelvic radiotherapy following surgery and chemotherapy in advanced ovarian cancer

Thirty advanced ovarian cancer patients have been treated with sequential multimodality treatment including primary surgery, cisplatin or carboplatin-based polichemotherapy, second-look laparotomy followed by abdominopelvic irradiation (moving strip or open-field technique). Toxicity related to the combined treatment was acceptable: only three patients failed to complete and two patients delayed the prescribed course of radiotherapy because of acute myelosuppression or gastroenteric disturbances. One patient without evidence of disease required laparotomy for bowel obstruction one month after completion of radiotherapy. No other chronic toxicity of clinical significance has been observed. Actuarial three-year survival significantly correlated with residual disease at the start of radiotherapy: no residuum, 100%, microscopic disease, 52%; <2cm macroscopic disease, 27.4% (P<0.05), whereas recurrences were less frequent only in the group of pathological complete responders (3/9) compared to patients with limited disease (6/1 with micro and l7/10 with macroscopic residuum). In conclusion radiotherapy following surgery and chemotherapy is not associated to serious morbidity but its value in improving progression-free survival rates has to be tested in randomized trials.     

Microscopic disease at second-look laparotomy in advanced ovarian cancer

During the 11-year interval from January 1971 to January 1982, 50 of 246 patients with advanced (Stage III and IV) epithelial ovarian carcinoma at second-look laparotomy had biopsy or cytologic evidence of persistent microscopic carcinoma. The stage and grade profile include 46 Stage III and 4 Stage IV patients: 4 borderline, 9 grade 1, 20 grade 2 and 17 grade 3 patients. Following second-look laparotomy, 4 patients received no further therapy, 45 received chemotherapy, and 1 received external radiation. No patient was lost to follow-up, and the median interval off therapy was 24 months. Progressive or recurrent disease has manifest in 12 (24%). No recurrences have developed either in patients younger than age 40 or in patients with grade 1 tumors. Two patients died of leukemia, 1 died of heart disease, and 35 (70%) are alive with no evidence of disease. In patients developing recurrence, the median progression-free interval was 17.5 months, with a range of 6 to 46 months. The median interval of survival following disease progression was 7 months. There was no evidence of progression at 2 years and 5 years in 81% and 70% of patients, respectively. The uncorrected 2- and 5-year survival rates were 96% and 71%, respectively. The 5-year survival rates for grades 1, 2, and 3 were 100%, 79%, and 36%, respectively. Other variables analyzed include number of positive foci, residual tumor volume at initial surgery, cytologic findings at second-look laparotomy, type of chemotherapy, and number of courses of chemotherapy before second-look laparotomy. In summary, patients with only microscopic evidence of disease at second-look surgery have a good probability for extended survival.     

Intraperitoneal chromic phosphate therapy after second-look laparotomy for ovarian cancer

Between 1973 and 1985, 118 patients in clinical remission after initial surgery and postoperative chemotherapy for epithelial ovarian carcinoma underwent second-look laparotomy at the University of North Carolina. No evidence of disease (NED) was found in 57 of these patients; 43 patients received 15 mCi of radioactive chromic phosphate (32P) suspension given intraperitoneally in the immediate postoperative period. In 29 other patients, only microscopic or minimal residual disease (nodules less than 2 cm in size) was found, seven received 32P alone, ten received 32P and further chemotherapy, and 12 received chemotherapy alone. The 4-year postsecond-look survival of the patients with NED at second-look was 89% for those receiving 32P and 67% for those who had not. The respective figures for patients with minimal residual disease at second-look are 59% versus 22%. Irrespective of treatment, a group at high risk for failure after negative second-look laparotomy has been identified; those with an initial International Federation of Gynecology and Obstetrics (FIGO) stage greater than I and histologic grade greater than 1. A comparison of our data with 18 previously published series, indicates that use of postsecond-look intraperitoneal 32P can improve the progression-free interval, and possibly overall survival, of patients with NED or minimal residual disease without adding significant complications.     

Primary cytoreductive surgery with rectosigmoid colon resection for patients with advanced epithelial ovarian carcinoma

BACKGROUND: The impact of radical bowel resection with multiple organ resection on the survival if patients with advanced ovarian carcinoma has not been well defined. The authors investigated whether primary cytoreductive surgery including rectosigmoid colon resection would affect the recurrence free interval and survival of these patients. METHODS: Between April 1990 and April 1997, 66 previously untreated Stage IIIC-IV ovarian carcinoma patients with macroscopic involvement of the rectosigmoid colon were enrolled. All patients underwent cytoreductive surgery with rectosigmoid colon resection to remove residual tumor less than 2 cm in greatest dimension and received 6 cycles of cisplatin-based postoperative chemotherapy. RESULTS: The median follow-up was 26 months (range, 7-104 months). In multivariate analysis, residual disease and depth of tumor infiltration of the bowel wall were independently associated with overall survival and recurrence free interval. Disease stage was independently associated only with overall survival. Residual tumor was the most strongly predictive factor for recurrence or death. The 2-year estimated survival rates according to the amount of residual tumor were 100% for 24 patients with no macroscopic residual disease and 77.3% for 28 patients with residual disease less than 1 cm. None of the 14 patients with residual disease larger than 1 cm were alive 2-years after operation. Overall, 48 patients (72.7%) developed disease recurrence: 43 (65.1%) in the abdomen, 19 (29.8%) in the liver, and 3 (4.5%) in the pelvis. CONCLUSIONS: The current findings suggest that cytoreductive surgery with rectosigmoid colon resection should be considered for ovarian carcinoma patients with bulky pelvic disease to help ensure that they are left with no residual disease after debulking surgery.     

晚期上皮性卵巢癌肠肿瘤切除的作用

目的：分析晚期上皮性卵巢癌行肿瘤细胞减灭术时肠道转移瘤行肠道肿瘤切除的临床应用。方法：回顾性分析1998～2003年52例晚期上皮性卵巢癌行肿瘤细胞减灭术时肠道转移瘤行肠道肿瘤切除的患者,与同期未行肠道肿瘤切除的仅行姑息性手术的16例患者进行比较,采用统计学方法进行处理。结果：68例手术治疗患者中,52例完成肠道肿瘤切除手术,其中34例无肉眼呵见残余肿瘤,8例残余肿瘤〈1cm,10例残余肿瘤〉1cm,其中位生存期分别为28个月、23个月和13个月,16例因肿瘤广泛转移未行肠道肿瘤切除仅行姑息性手术的患者中位生存期为7．66个月,肠道肿瘤广泛转移及肠系膜根部广泛种植是手术失败的关键。结论：晚期上皮性卵巢癌行肿瘤细胞减灭术时行肠道转移瘤切除,达到满意手术效果时对生存期提高足有帮助的,而选择恰当的患者是手术治疗的关键。     

Prognosis of surgically determined complete responders in advanced ovarian cancer

From January 1971 through December 1981, 246 patients with advanced (Stages III and IV) epithelial ovarian cancer underwent second-look laparotomy at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston. Eighty-five of these patients had a complete response (negative second-look laparotomy) following treatment with a variety of chemotherapeutic regimens. Three patients had also received irradiation. Patients were analyzed according to pretreatment characteristics (age, FIGO stage, ascites, pleural effusion, histologic grade, tumor type, type of surgery, residual tumor diameter, initial clinical status) and by the number of biopsy specimens taken at second-look laparotomy. The probability of recurrence and the length of survival following a negative second-look laparotomy are statistically related to these characteristics. Twenty of the 85 patients (24%) developed recurrent disease 5 to 32 months after laparotomy. The estimated 2- and 5-year survival rates are 99% and 85%, respectively. Patients who achieve a surgically determined complete response have an excellent chance for long-term survival.     

Whole abdominal irradiation following chemotherapy in patients with minimal residual disease after second look surgery in ovarian carcinoma

From January 1981 through December 1985, 65 patients with epithelial carcinoma of the ovary were treated with the following protocol: surgery, combination chemotherapy, second-look surgery documenting tumor less than or equal to 2 cm, and whole abdominal irradiation. Chemotherapy consisted of a combination of cyclophosphamide, adriamycin, and cisplatinum in 89% of the patients. The median number of cycles was eleven. Second-look surgery documented no residual tumor in 23 patients, microscopic disease in three patients, and macroscopic disease less than or equal to 2 cm in 39 patients. Whole abdominal irradiation was given with an open field technique up to 20 Gy without renal or hepatic shield. A pelvic boost of 15-30 Gy was subsequently added in 17 patients with macroscopic disease in the pelvis at the time of second-look surgery. Fifteen patients received complementary chemotherapy mostly hexamethylmelamine. All but two patients completed whole abdominal irradiation: one refused further radiotherapy after 3 Gy and one developed disease progression with bowel obstruction after 1 Gy. The median follow-up was 69 months. The 3-year and 6-year no evidence of disease survival rates were 60% (95% CI: 48-71) and 33% (95% CI: 21-46), respectively. The 3-year and 6-year recurrence rates were 33% (95% CI: 22-45) and 54% (95% CI: 40-67), respectively. The 3-year and 6-year metastasis rates were 22% (95% CI: 13-34) and 43% (95% CI: 30-58), respectively. A multivariate analysis showed that residual disease after second-look surgery was the only significant prognostic factor with a relative risk of death or local or distant failure of 4.2 (95% CI: 1.9-9.5, p less than 10(-4)). Two patients developed mean-term gastrointestinal complications (small bowel obstructions requiring surgery). Survival remains poor with high level of failure even with aggressive multimodal treatment.     

腹腔镜检在孵巢癌二次探查术中的价值

对３８例术后多疗程化疗后临床常规检查无肿瘤征象的卵巢癌患者进行腹腔镜检结合剖腹探查。结果：镜下发现可疑病灶１４例，术后病理阳性９例；２４例镜下阴性者，术后病理阳性７例。腹腔镜下诊断与剖腹探查病理检查结果相对照，其诊断的敏感性为６４．３％，特异性为７０．８％，准确性为６８．４％。因此，腹腔镜检在卵巢癌二探术中有一定的临床诊断价值。尤其是对膈下病灶的发现有独到之处，但尚不能完全替代剖腹二次探查术。     

Single agent vs. combination chemotherapy for ovarian cancer

Forty evaluable patients with advanced epithelial cancers of the ovary received chemotherapy. Twenty-seven previously untreated patients underwent a 1:1 randomization between a combination of Cytoxan, Hexamethylmelamine, and Fluorouracil (CHF) versus a single agent, L-phenylalanine mustard (L-pam). Thirteen patients previously treated with other therapies received CHF as a second-line therapy. Eighty-five percent of the patients receiving triple therapy were responders, versus 57% in the single agent group. Fifty percent of the CHF group had a complete response versus 17% in the L-pam group (p = 0.09). All patients with complete resection of less than 2 cm residual disease at primary surgery were responders, regardless of the type of therapy. Response in these patients is defined in terms of disease-free interval. The importance of maximal surgical resection in management of these cancers is discussed. Five of eight patients treated with CHF undergoing second-look operations had no evidence of disease. One of three L-pam treated patients had no evidence of disease at second-look surgery. Six of 13 patients (46%) had partial response to CHF as a second-line drug.     

Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy

The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy. © 1996 Wiley-Liss, Inc.     

How does negative clinical evaluation of ovarian carcinoma after full course of chemotherapy correlate with second-look laparotomy findings?

Surgical reexploration was performed in 46 patients with epithelial nonmucinous ovarian adenocarcinoma requiring adjuvant chemotherapy whose initial therapy consisted of optimum debulking and surgical staging. All patients were placed on CAP (cisplatinum, Adriamycin, cyclophosphamide) chemotherapy for at least six courses until proved to be clinically disease free (mainly CA-125 below 35 U/ml and normal ultrasonography or computerized tomography). All women underwent second-look laparotomy (SLL) after completion of adjuvant therapy. We classified SLL findings in five categories, namely, no evidence of disease, cytological evidence of disease, histological evidence of disease, macroscopic evidence of disease (<2 cm), and bulky tumor (>2 cm). SLL demonstrated 14 (30%) patients with disease. Of these, five cases had histological evidence of disease and nine had macroscopic disease; however, we found no patient with persistent disease larger than 1.5 cm. No patient in stage I demonstrated disease at SLL. All cases with macroscopic disease and three cases with histological disease were initially in stage III. We found that about one third of cases who were clinically free of disease had persistent disease at the completion of chemotherapy. Hence, we conclude that routine SLL is still of importance in the management of patients with epithelial ovarian adenocarcinoma except those with stage I disease. © Wiley-Liss, Inc.     

Twice-daily, split-course abdominopelvic radiation therapy after chemotherapy and positive second-look laparotomy for epithelial ovarian carcinoma

Between July 1983 and December 1988, 34 patients with ovarian carcinoma received whole abdominal irradiation in an attempt to eliminate residual disease following second-look laparotomy. Three additional patients who had initial complete responses to chemotherapy were treated for a recurrence of their disease. All patients had been treated with chemotherapy that included cisplatin and cyclophosphamide. Three patients had also received doxorubicin with some or all chemotherapy cycles. Thirty Gray of abdominopelvic radiation therapy (APRT) was delivered using a twice-daily, split-course schedule. Eleven patients also had a boost of 9-20 Gy to sites of residual disease. Treatment was well tolerated. Only one patient did not complete therapy and two patients had 1-week prolongations of treatment because of hematologic toxicity. Thirty-two percent of patients had grade 2 neoplasms and 61% had grade 3 disease. Three patients with grade 1 tumors continue to have no evidence of disease 20-50 months after irradiation. Patients with grade 2 and 3 neoplasms who had microscopic residual disease prior to APRT had relapse-free survival rates at 3-years of 10% and 14%, respectively. Twelve patients with gross residual disease had rapid recurrences (median time to relapse, 4.9 months) and all have died of their disease. Although 14 patients (38%) have experienced small bowel obstructions, all of these had known recurrent abdominal disease at the time. Twenty patients (54%) had undergone more than two abdominal surgeries prior to APRT, and several were noted to have extensive adhesions at second-look laparotomy. None of the five patients currently believed to be free of disease has experienced a small bowel obstruction. Radiation is only one of several factors that contributed to bowel obstructions. Although APRT may be able to eliminate residual disease in a small proportion of patients with microscopic residual disease after chemotherapy, the aggressive biology of tumors that respond incompletely to chemotherapy and the compromises in radiation dose and schedule that must be made in these heavily treated patients probably contribute to the disappointing results of this treatment.     

Significance of cytoreductive surgery including bowel resection for patients with advanced ovarian cancer.

The aim of this study was to determine the significance of bowel resection in advanced ovarian cancer. A total of 64 women with stage IIIc or IV epithelial ovarian cancer, who consecutively received primary treatment between 1991 and 1995, were entered in this prospective study. The outcome of the patients undergoing bowel resection was evaluated. Thirty-nine patients underwent cytoreductive surgery at initial surgery. Of them, 16 patients could undergo optimal operation without bowel resection. Twenty-three patients received bowel resection at initial surgery. Of these 23 patients, 16 underwent optimal operation and 7 did not. Among 25 patients judged as inoperable cases at initial surgery, 21 responded to chemotherapy and underwent second surgery. Of 21 patients receiving second surgery, 15 underwent optimal operation (7 without bowel resection and 8 with bowel resection). The 3-year survival rate for 24 patients undergoing optimal operation with bowel resection (46.8%) was not significantly different from that for 23 patients without bowel resection (59.1%). Postoperative complications were seen in 8 patients (21.6%) of the patients receiving bowel resection and 3 (13.0%) of those without bowel resection. Cytoreductive surgery including bowel resection is effective for an improvement of the survival in patients with advanced ovarian cancer, if an optimal operation can be performed.     

Survival with intraperitoneal cisplatin in advanced ovarian cancer after second-look laparotomy.

We studied survival in 36 patients with Stage III/IV ovarian cancer who received intraperitoneal high-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g), after intravenous (i.v.) cisplatin-based chemotherapy followed by second-look laparotomy. Complete responders were scheduled for three courses of IP chemotherapy, and others for six. Eight patients (22%) did not complete treatment (6 catheter failures and 2 renal failures). Peritoneal cytology remained positive in 6 patients (17%). Median overall and progression-free survival after second-look laparotomy were 44 and 37 months, respectively, for 13 complete responders to i.v. chemotherapy; 24 months and 11 months for patients with residual tumors less than 2 cm (17 cases); 15 and 12 months with tumors greater than 2 cm (6 cases). There was a significant difference in overall (p = 0.05) and progression-free (p = 0.001) survival between complete responders to i.v. chemotherapy and patients whose tumor was less than 2 cm. We find no evidence that high-dose cisplatin-based intraperitoneal chemotherapy given after second-look laparotomy will enhance survival in advanced ovarian cancer with zero or minimal residual disease.     

Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.     

Cisplatin-containing versus cisplatin-free adjuvant chemotherapy in ovarian carcinoma. Results after second-look laparotomy

In 1980, second-look laparotomy was introduced simultaneously into the treatment regimen for ovarian carcinoma at the two main referral centers of northern Spain. First-line chemotherapy after initial surgery was, however, different at both hospitals. At one of them (Bilbao), a combination involving the use of cisplatin was employed (cyclophosphamide 600 mg/m2, Adriamycin 45 mg/m2, and cisplatin 80 mg/m2 i.v. on day 1), whereas the patients of the other hospital were treated mainly with single-agent chemotherapy (melphalan 0.2 mg/kg p.o. on days 1-5) and never with a cisplatin combination as first-line therapy in any case. In all, 92 patients (42 stage I, 14 stage II, 33 stage III, and 3 stage IV) could be treated during the study period with optimal surgery (complete tumor excision or largest residual tumor less than 2 cm in diameter). This was followed by adjuvant chemotherapy for 12-18 months in all cases, except for 18 patients with a stage Ia borderline or G1 tumor. The latter were merely kept under observation until their second-look laparotomy after 1 year of negative follow-up. All of the 74 patients who received adjuvant chemotherapy, of whom 36 with cisplatin and 38 without, were clinically disease free after at least twelve courses of treatment and had a second-look laparotomy performed. This was positive in 33.3% of the cases after cisplatin-containing therapy and in 26.3% of the cases after cisplatin-free therapy. This difference is not statistically significant. The mean follow-up period after negative second-look was 34 months. The long-term results of both patient groups were comparable as far as rate of positive second-look laparotomies and survival rate, overall and stage for stage are concerned. The use of cisplatin did not result in any significant therapeutic improvement. It was uniformly bad tolerated by the patients and carried higher cost, since all patients had to be hospitalized for treatment.     

The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma

Forty consecutive patients with stage III and IV invasive ovarian carcinoma were treated on a phase II protocol consisting of optimal debulking surgery, induction cisplatin, cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy, 6-month interval laparoscopy, reinduction cisplatin, PAC chemotherapy, and second-look procedure. All 40 patients have either disease progression or have completed the 12-month protocol. Eighty-seven percent of the patients (35) underwent optimal (less than or equal to 2 cm residual) debulking surgery before chemotherapy, in spite of the fact that 50% (20) were referred to Roswell Park Memorial Institute (RPMI) as inoperable after initial surgery elsewhere. There were no postoperative deaths and chemotherapy was started in less than or equal to 14 days in 97% of the patients. Of the 40 patients, 30% (12) achieved a pathologic complete remission (11) or a clinical complete remission (one patient refused second-look surgery). The estimated 3-year survival rate was 62%, but the 3-year progression-free survival rate was only 29%. The median survival time was 48 months. The estimated 3-year progression-free survival rate was 31% for residual disease less than or equal to 2 cm. For the five patients with residual disease greater than 2 cm, four died within 3 years. The median survival time of patients with less than or equal to 2 cm residual disease was 48 months, as compared with 21 months for those with greater than 2 cm residual disease. Although the estimated 3-year survival rate of 62% is noteworthy, the 3-year progression-free survival rate of only 29% is probably indicative that in spite of extensive debulking surgery and cisplatin-based chemotherapy as used in this protocol, the long range proportion of patients "cured" will remain small.