The number of futile laparotomies was decreased in patients with advanced-stage ovarian cancer who underwent diagnostic laparoscopies, according to the results of a study in the Journal of Clinical Oncology.
The multicenter, randomized controlled trial, which was conducted in the Netherlands, investigated whether diagnostic laparoscopy could prevent futile primary cytoreductive surgery (PCS) by identifying patients with advanced ovarian cancer in whom more than 1 cm of residual disease will be left following PCS.
“We performed the first randomized multicenter study to investigate the role of laparoscopy to make a decision to start with primary cytoreductive surgery or neoadjuvant chemotherapy,” study author Marrije R. Buist, M.D., Ph.D., gynecologic oncologist, Department of Gynecologic Oncology, Academic Medical Center, Center of Gynecologic Oncology, in Amsterdam, said in an interview with CURE.
“Our major finding is that a diagnostic laparoscopy in patients with a suspicion of ovarian cancer with metastases before the start of primary cytoreductive surgery can prevent a primary laparotomy with more than 1 cm residual disease. In these patients, an interval cytoreductive surgery is a better option after neoadjuvant chemotherapy,” added Buist.
Of 201 patients included in the study, 102 were assigned to diagnostic laparoscopy, and 99 patients were assigned to primary surgery. In the laparoscopy arm, 63 of 102 patients (62 percent) underwent PCS versus 93 of 99 patients (94 percent) in the primary surgery group. Futile laparotomy — residual tumor with a maximum diameter of more than 1 cm after PCS — was observed in 10 of 102 patients (10 percent) in the laparoscopy group versus 39 of 99 patients (39 percent) in the primary surgery arm of the trial. Three of 102 patients (3 percent) in the laparoscopy group underwent both primary and interval surgery, compared with 28 of 99 patients (28 percent) in the primary surgery group.
Patients between the ages of 18 and 80 with suspected advanced-stage ovarian cancer (FIGO stage 2B or higher) across eight gynecologic cancer centers in the Netherlands were eligible for the study whenever PCS seemed possible after conventional diagnostic workup. They were randomly assigned (1 to 1 ratio) to either diagnostic laparoscopy or PCS followed by chemotherapy.
An open laparoscopy was performed within three weeks after random assignment to inspect the whole abdomen in a systematic fashion. The decision about whether cytoreduction to less than 1 cm of residual disease was feasible or not was made by the gynecologic oncologist on the basis of the following laparoscopic findings: extensive agglutinated intra-abdominal metastatic disease, extensive serosa invasion of the intestines and/or mesenterial deposits, and irresectable peritoneal metastases at the diaphragmatic level. If PCS could leave at least 1 cm of residual disease, the procedure was performed and then followed by six cycles of chemotherapy. If it was deemed not feasible at laparoscopy for PCS to remove all tumor to less than 1 cm of disease, patients were primarily treated with three courses of neoadjuvant chemotherapy followed by interval cytoreductive surgery.
Patients in the arm without diagnostic laparoscopy were all assigned to PCS, with the goal of surgery in all cases being resection of all macroscopic tumors.
In both groups of patients, a second laparotomy was considered after three cycles of chemotherapy, in the event that more than 1 cm of residual tumor was left after the first attempt at surgery.
Follow-up consisted of visits every three months for the first two years, followed by visits every six months for up to five years.
The primary outcome measure of the study was a futile laparotomy, which the authors defined as residual tumor with a maximum diameter of more than 1 cm after PCS. The investigators ultimately sought to guide treatment decisions for either PCS or interval cytoreductive surgery, to reduce the number of patients subjected to multiple laparotomies, and to select patients who are best suited for PCS. Secondary outcomes in the study included adverse events, progression-free survival (PFS) and overall survival (OS).
Of 201 patients included in the intention-to-treat analysis, 102 were assigned to laparoscopy prior to surgery, and 99 patients were assigned to PCS. Baseline characteristics were well balanced between the two arms of the study.
In the laparoscopy group, 62 percent of patients (63 patients) were treated with PCS after laparoscopy, and 38 percent of patients (39 patients) were assigned to neoadjuvant chemotherapy followed by interval surgery. Reasons for withholding from PCS were mostly attributed to extensive agglutinated intra-abdominal metastatic disease and extensive peritoneal metastases at the diaphragmatic level. In four of these patients in the laparoscopy arm, no cytoreductive surgery was attempted due to progression while being treated with chemotherapy or inoperability because of poor general condition.
Ninety-four percent of patients (93 patients) in the primary surgery arm underwent PCS. One patient falsely received a diagnostic laparoscopy, and she was assigned thereafter to neoadjuvant chemotherapy. Five patients in the primary surgery arm of the study experienced deterioration in physical condition after random assignment and were considered unfit to receive PCS. They were treated with neoadjuvant chemotherapy instead. Four patients in this group received interval surgery.
Futile laparotomy that left more than 1 cm of residual disease following primary surgery was observed in 10 of 102 patients (10 percent) in the laparoscopy group, versus 39 of 99 patients (39 percent) in the primary surgery group. In the laparoscopy arm, 27 of 102 patients (27 percent) had any residual tumor (more than 0 cm) versus 56 of 99 patients (57 percent) in the primary surgery arm. A subgroup analysis of patients with confirmed stage 3C or 4 ovarian cancer showed that only six of 71 (8 percent) patients in the laparoscopy group received a futile laparotomy compared with 32 of 69 (46 percent) of patients in the primary surgery group.
Four of 102 patients (4 percent) in the laparoscopy group underwent both primary and interval laparotomy, versus 28 of 99 patients (28 percent) in the primary surgery group (P <.001).
The investigators also carried out analyses of the differences in the amount of residual disease per surgical strategy (primary or interval). In the laparoscopy group, no residual tumor was found in 36 of 63 patients (57 percent) who underwent PCS, versus 37 of 93 patients (40 percent) in the primary surgery group (P = .006) and in 14 of 34 patients (41 percent) and 16 of 63 patients (25 percent) in the subgroup with stage IIIC or IV ovarian cancer, respectively. Complete remission following surgery and chemotherapy was observed in 65 of 99 patients (66 percent) in the laparoscopy arm versus 65 of 95 patients (68 percent) in the primary surgery arm.
In the laparoscopy group, the median duration of follow-up was 34.6 months, versus 33.8 months in the primary surgery group. Forty-six patients in the laparoscopy group and 42 patients in the primary surgery group had died at the last time of follow-up. This indicates comparable survival between the two treatment arms.
The median PFS was 13.7 months in the laparoscopy group and 15.2 months in the primary surgery group. The median OS was 44.4 months in the laparoscopy arm and 46.3 months in the primary surgery group with a hazard ratio of 1.33. In terms of safety, 22 patients in the laparoscopy group experienced a grade 3 or 4 adverse event versus 26 patients in the primary surgery group.
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