Interval cytoreduction in advanced ovarian cancer : Santa Casa São Paulo experience

Objective: To analyze the interval cytoreduction in patients with advanced ovarian cancer. Methods: A prospective study was carried out with 25 patients with advanced ovarian cancer (stages IIIC or IV) who underwent interval cytoreduction. Nonresectability criteria were based on the ones from Gustave-Rousy Institute. After induction chemotherapy and rapprochement we evaluated the rates of optimal surgery and the morbidity and mortality of the procedure in addition to the overall survival at two years. Results: optimal cytoreduction was possible in 17 patients (68%) with morbidity and mortality from 8% to 4%. The overall survival at two years was 68%. Conclusion: The interval cytoreduction is an alternative therapy in advanced ovarian cancer, allowing optimal cytoreduction opportunity to patients suffering from unresectable disease, with acceptable morbidity


INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION INTRODUCTION
O varian cancer has the highest fatality rate among gynecological tumors; in Brazil about 3500 new cases/year, with 2000 deaths/year, are estimated 1 .
So far there are no effective tracking methods for early detection of this neoplasia, only 25% being diagnosed in early stages.Despite optimal advances in chemotherapy and surgical treatment, the survival rate for ovarian carcinoma has remained steady in recent decades, with a 30% overall survival at five years 2 .
Since the pioneering work of Griffiths in 1975 to the present day, numerous studies show that the optimal primary cytoreduction, i.e. the residual tumor less than 1 cm, implies survival gain [3][4][5][6] .However, this can only be reached in 50% of patients with advanced disease, not being exempt of morbidity and mortality, 30% and 10% respectively 7 .
To improve surgery optimal rates, as well as decrease primary debulking's morbidity, comes the interval laparotomy, which consists of reapproach after neoadjuvant chemotherapy for patients with non-resectable disease or poor result from the first laparotomy 8 .
In view of the evidence that present interval laparotomy as a therapeutic option to primary cytoreduction , showing similar survival but with lower morbidity and mortality, we felt motivated to study this approach in patients with advanced carcinoma of the ovary in our institution.

METHODS METHODS METHODS METHODS
In the period from September 2004 to January 2007, after approval of the Committee of Ethics in Research of Santa Casa de Misericórdia de São Paulo (Protocol number 424/06), we carried out a prospective study of 25 patients with advanced carcinoma of the ovary (IIIC or IV) initially submitted to laparotomy during which nonresectable disease was diagnosed and a biopsy was performed.Irresectability criteria were based on the Institute Gustave-Rousy 9 , which were the presence of at least one of these factors; resection of more than three segments of intestine, splenopancreatectomy, liver resection, presence of lymph nodes larger than 2 cm, "frozen pelvis", difuse carcinomatosis or invasion of the root of the mesentery.
We employed a neoadjuvant chemotherapy protocol with paclitaxel 175 mg/m 2 and carboplatin AUC 5 every 21 days in three cycles.In the sequence, patients were examined and evaluated by abdomen and pelvis CT and CA 125 dosage.In the absence of disease progression, patients were subjected to interval laparotomy with the goal of optimal cytoreduction.
After reapproach we evaluated the rate of optimal surgery, as well as the morbidity and mortality of the procedure and overall survival in two years.

RESULTS RESULTS
We were able to perform optimal cytoreduction in 17 patients (68%).The standard procedure, i.e., hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and omentectomy, was performed in 13 patients, and there was need for extended resection in 12 (Table 1).The results of our initial experience with interval laparotomy are exposed in table 2.

DISCUSSION
DISCUSSION DISCUSSION DISCUSSION DISCUSSION Van der Burg et al. 10 , comparing interval laparotomy with chemotherapy in 278 patients with stages IIB and IV 11 ovarian carcinoma subjected to initial suboptimal cytoreduction , observed a disease-free survival in two years of 56% for the group that underwent laparotomy versus 46% for the control group, submitted to chemotherapy alone (p < 0.01).They concluded that interval laparotomy presents a gain survival when compared to chemotherapy alone for patients subjected to initial sub-optimal cytoreduction 10 .However, these data has not been demonstrated in the study GOG152 11 .
Morice et al 12 compared patients subjected to interval laparotomy with the one submitted to primary cytoreduction and obtained optimal cytoreduction rates of 94% in both groups.Nevertheless, morbidity in the interval laparotomy Group was lower than that of primary cytoreduction.After five years of follow-up, the rates of overall survival were 24% in both groups.The authors concluded that, although there is no gain in survival with interval laparotomy, it is an effective therapy option, with less morbidity, for the treatment of advanced ovarian cancer 12 .
Chan et al 13 .used a EORTC (QLQ-C30) questionnaire to assess the quality of life of patients with stages III and IV submitted to interval laparotomy or primary cytoreduction.They demonstrated that the group submitted to interval laparotomy presented better scores in the questionnaire in relation to the group that received conventional treatment 13 .
The purpose of this study was to evaluate the safety and efficacy of interval laparotomy in patients with advanced ovary carcinoma.Using this approach, we obtained cytoreduction in 88% of our patients, agreeing with the data from Onda et al 14 .As for the achievement of optimal surgery, our result of 77% (68%) was also consistent with the results found in the literature (50%-90%) 15 .
Morbidity of cytoreduction in advanced carcinoma of the ovary is 12% and in our service it was 8%.Perioperative mortality in our series was 4%, similar to the literature data 16 .
The need for an extended operation in interval laparotomy results from the more aggressive biological behavior of the tumor, with worse prognosis, and thus interval cytoreduction should only be performed with    17 .In this case extended resection was necessary in 48% of patients, and optimal cytoreduction occurred in 83%.
Our median of overall survival after 24 months was 68%, a result that corroborates with previous studies 18 .
Our data suggest that the interval cytoreduction is an alternate therapy in advanced carcinoma of the ovary, enabling an opportunity of optimal surgery for patients with formerly non-resectable disease, with acceptable morbidity and mortality.

Table 1 Table 1 -
Procedures performed on 12 patients subjected to interval laparotomy with extended operation for carcinoma of ovary.