Prognostic influence of an early time to chemotherapy following primary cytoreductive surgery for advanced epithelial ovarian cancer.

OBJECTIVE: The current investigation analyzes the prognostic role of the time to chemotherapy (TTC) interval following primary cytoreductive surgery for patients with advanced epithelial ovarian cancer. METHODS: Characteristics and outcome data for 509 consecutive patients with stage IIIB-IVB ovarian, fallopian tube, and peritoneal cancer who had primary cytoreductive surgery between January 2000 and December 2019 are utilized. A univariate Cox regression determined the association of categorical variables with progression-free survival (PFS) and overall survival (OS). Significant variables (p≤0.05) on univariate analysis were applied to Cox proportional hazard regression. RESULTS: The median TTC was 19 days and overall follow-up was 62.2 months. The PFS and OS were 25.5 months and 78.4 months for the study cohort plus 28.4 months and OS 84.5 months for patients rendered grossly disease-free. An early TTC (7-14 vs. 15-21 vs. 22-28 vs. >28 days) was associated with an improved PFS (41.7 vs. 30.6 vs. 18.9 vs. 17.9 months; p<0.001) and OS (132.7 vs. 104.6 vs. 56.5 vs. 48.0 months; p<0.001). The performance status, histology, disease distribution, dimension of residual disease, and categorical plus continuous TTC were predictors of PFS and OS. The use of maintenance therapy was also a predictor of PFS, and the route of chemotherapy administration was a predictor of OS. CONCLUSIONS: For advanced epithelial ovarian cancer, a TTC of less than 21-days was observed to independently improve the PFS and OS. A 7-14 days TTC trended towards a further extension of the OS.

Total Laparoscopic Hysterectomy with Pelvic/Aortic Lymph Node Dissection for Endometrial Cancer Using Passive Instrument Positioners: A Retrospective Case-Control Series.

STUDY OBJECTIVE: To investigate the influence of the use of passive instrument positioners (PIPs) on laparoscopic operative outcomes for endometrial cancer relative to other independent variables. DESIGN: Retrospective case-controlled study (Canadian Task Force classification II-2). SETTING: Laparoscopies performed by the author in multiple community hospitals. PATIENTS: A total of 297 consecutive patients between December 2009 and October 2016 with clinically isolated endometrial cancer or retroperitoneal lymphadenopathy on imaging studies. INTERVENTIONS: Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and pelvic/aortic lymph node dissection using passive instrument positioners to secure the laparoscope (PIP group) and using instruments providing exposure and historical control by hand control of all instruments (HC group). MEASUREMENTS AND MAIN RESULTS: The overall group mean age was 63.2 years (range, 32.4-90.9 years), and patient characteristics were equivalent in the 2 groups. In the PIP group, 1 procedure was converted to a laparotomy (0.5%), and in the HC group, 6 procedures were converted (5.4%; p = .008). The mean operative time was 140.1 minutes for the PIP group and 153.8 minutes for the HC group (p < .001). The mean length of hospital stay was 44.8 hours for the PIP group and 58.6 hours for the HC group (p < .001). Multivariate analysis confirmed that study group (PIP vs HC; p = .014) and the presence vs absence of metastatic disease (p = .001) influenced conversion; study group (PIP vs HC; p < .001), body mass index (p < .001), past surgical history (p = .010), and assistant training (p = .011) influenced operative time; and study group (PIP vs HC; p < .001), Eastern Cooperative Oncology Group performance status (p < .001), and operative time (p = .051) influenced hospital stay. CONCLUSION: For clinically localized endometrial cancer managed laparoscopically, the use of PIPs reduces conversions, operative time, and hospital stay.

Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study.

PURPOSE: The primary objective was to establish noninferiority of laparoscopy compared with laparotomy for recurrence after surgical staging of uterine cancer. PATIENTS AND METHODS: Patients with clinical stages I to IIA disease were randomly allocated (two to one) to laparoscopy (n = 1,696) versus laparotomy (n = 920) for hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The primary study end point was noninferiority of recurrence-free interval defined as no more than a 40% increase in the risk of recurrence with laparoscopy compared with laparotomy. RESULTS: With a median follow-up time of 59 months for 2,181 patients still alive, there were 309 recurrences (210 laparoscopy; 99 laparotomy) and 350 deaths (229 laparoscopy; 121 laparotomy). The estimated hazard ratio for laparoscopy relative to laparotomy was 1.14 (90% lower bound, 0.92; 95% upper bound, 1.46), falling short of the protocol-specified definition of noninferiority. However, the actual recurrence rates were substantially lower than anticipated, resulting in an estimated 3-year recurrence rate of 11.4% with laparoscopy and 10.2% with laparotomy, or a difference of 1.14% (90% lower bound, -1.28; 95% upper bound, 4.0). The estimated 5-year overall survival was almost identical in both arms at 89.8%. CONCLUSION: This study previously reported that laparoscopic surgical management of uterine cancer is superior for short-term safety and length-of-stay end points. The potential for increased risk of cancer recurrence with laparoscopy versus laparotomy was quantified and found to be small, providing accurate information for decision making for women with uterine cancer.

Total laparoscopic hysterectomy with pelvic/aortic lymph node dissection for endometrial cancer--a consecutive series without case selection and comparison to laparotomy.

OBJECTIVE: To determine feasibility of duplicating operative time and nodal yield of "open" procedures by using laparoscopy for clinically localized endometrial cancer without case selection and eliminating influence of BMI on conversion. METHODS: In this retrospective study 210 consecutive patients were laparoscoped between July, 2006 and November, 2009 to perform total laparoscopic hysterectomy with bilateral salpingoophorectomy and pelvic/aortic lymph node dissection (TLH/BSO/LND) using pulsed bipolar cautery to complete all phases of the procedure. Outcomes ("Scope" group) are compared to historic consecutive TAH/BSO/LND controls ("Open" group) operated on 2004-2009 and "open" series in the literature. RESULTS: Two hundred (95.2%) procedures were completed laparoscopically, 3 (1.4%) required a minilaparotomy to remove the uterus, and 7 (3.3%) were converted to complete the hysterectomy with some portion of LND. There was no influence of BMI (P=0.688), age (P=0.748) or the number of prior abdominal operations (P=0.875) on probability of conversion (Logistic regression). The mean age, BMI, number of prior abdominal procedures, and GOG performance status were equivalent in both study groups. The mean operative time was 139.5 min (IQR 125-152) for the "Scope" group and 128.4 min (IQR 105-124) for the "Open" group (P=0.008). The mean nodal yield was 34.7 (IQR 24-40) for the "Scope" group and 25.7 (IQR 18-30) for the "Open" group (P<0.001). The mean hospital stay was 3.2 days (IQR 2-4) for the "Scope" group and 7.9 days (IQR 5-9) for the "Open" group (P<0.001). CONCLUSIONS: For clinically localized endometrial cancer, TLH/BSO/LND can functionally duplicate operative time equivalent to "open" procedures, while improving nodal yield, and minimizing influence of BMI on conversion to laparotomy and case selection.

Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.

PURPOSE: The objective was to compare laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer. PATIENTS AND METHODS: Patients with clinical stage I to IIA uterine cancer were randomly assigned to laparoscopy (n = 1,696) or open laparotomy (n = 920), including hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The main study end points were 6-week morbidity and mortality, hospital length of stay, conversion from laparoscopy to laparotomy, recurrence-free survival, site of recurrence, and patient-reported quality-of-life outcomes. RESULTS: Laparoscopy was initiated in 1,682 patients and completed without conversion in 1,248 patients (74.2%). Conversion from laparoscopy to laparotomy was secondary to poor visibility in 246 patients (14.6%), metastatic cancer in 69 patients (4.1%), bleeding in 49 patients (2.9%), and other cause in 70 patients (4.2%). Laparoscopy had fewer moderate to severe postoperative adverse events than laparotomy (14% v 21%, respectively; P < .0001) but similar rates of intraoperative complications, despite having a significantly longer operative time (median, 204 v 130 minutes, respectively; P < .001). Hospitalization of more than 2 days was significantly lower in laparoscopy versus laparotomy patients (52% v 94%, respectively; P < .0001). Pelvic and para-aortic nodes were not removed in 8% of laparoscopy patients and 4% of laparotomy patients (P < .0001). No difference in overall detection of advanced stage (stage IIIA, IIIC, or IVB) was seen (17% of laparoscopy patients v 17% of laparotomy patients; P = .841). CONCLUSION: Laparoscopic surgical staging for uterine cancer is feasible and safe in terms of short-term outcomes and results in fewer complications and shorter hospital stay. Follow-up of these patients will determine whether surgical technique impacts pattern of recurrence or disease-free survival.

"Optimal" cytoreduction for advanced epithelial ovarian cancer: a commentary.

OBJECTIVE: To derive the most appropriate threshold to classify primary cytoreductive operations as "optimal" and address the clinical significance of this issue. METHODS: Criteria used to classify primary cytoreductive outcomes are reviewed. Survival outcomes are analyzed to address relative influences of the completeness of cytoreduction and "biological aggressiveness", as manifested by the extent of intra-abdominal metastases. RESULTS: Most cohorts analyzing relative influences of metastatic tumor burden and the dimension of residual disease on survival report completeness of cytoreduction to influence the prognosis more significantly than tumor burden, with necessity to perform various procedures having minimal or no influence. Equivalent survival is reported for completely cytoreduced patients with stage III disease whether substages IIIa/b (smaller tumor burden) are excluded or included. However, some stage IIIc series report more favorable median and 5-year survivals for small fractions of completely cytoreduced patients than series with a large visibly disease-free fraction. Increasing fractions of complete cytoreduction are reported in recent cohorts, without increase in morbidity. CONCLUSIONS: Complete primary cytoreduction improves the prognosis for survival significantly more than a small dimension of residual disease. Although prospective randomized trials addressing surgical issues have not been undertaken and numerous variables may reflect "biological aggressiveness" by influencing the prognosis, available data justify elimination of macroscopic disease to be the most appropriate objective of primary cytoreductive surgery. Stratification of survival by dimensions of residual disease in an investigational setting should include a visibly disease-free subgroup and if used, the term "optimal" should be applied to patients undergoing complete cytoreduction.

Splenectomy in the context of primary cytoreductive operations for advanced epithelial ovarian cancer.

OBJECTIVE: To determine if the need to perform splenectomy due to metastatic disease in the context of complete primary cytoreduction for ovarian cancer diminishes the prognosis for survival. METHODS: Between 1990 and 2004, 356 stage IIIC epithelial ovarian cancer patients underwent resection of all visible disease before systemic platinum-based combination chemotherapy. Forty-nine (13.8%) required a splenectomy due to metastatic disease. Survival was analyzed (log rank) on the basis of whether splenectomy was necessary. The frequency of performing other procedures, operative time, blood loss, transfusion rate, and hospitalization, was compared (Chi-square test; discrete and binomial data, t test; continuous data) on the basis of whether a splenectomy was required. RESULTS: Survival was not influenced (log rank) by the requirement of splenectomy (required; median 56.4 months, estimated 5-year survival of 48% vs. not required; median 76.8 months, estimated 5-year survival of 58% P = 0.4). The splenectomy subgroup more commonly required en-bloc resection of reproductive organs with rectosigmoid (89.8% vs. 55.7%, P < 0.001), diaphragm stripping (63.3% vs. 33.6%, <0.001)), full-thickness diaphragm resection (28.6% vs. 9.4%, P < 0.001), and resection of grossly positive retroperitoneal nodes (67.3% vs. 46.3%, P = 0.006). The splenectomy group had a longer operative time (238 min vs. 192 min, P = 0.004), estimated blood loss (1663 ml vs. 1167 ml, P = 0.001), transfusion rate (5.3 units prbc vs. 3.2 units prbc, P = 0.002), and hospitalization (16.1 vs. 12.2 days P = 0.001). CONCLUSIONS: The need for splenectomy to achieve complete cytoreduction is a reflection of advanced disease but is not a manifestation of tumor biology precluding long-term survival.

Division of pedicles by stapling during cytoreductive surgery for ovarian cancer.

OBJECTIVE: To determine the potential of dividing vascular pedicles by stapling to reduce operative time, blood loss, and morbidity associated with cytoreductive operations for advanced ovarian cancer. METHODS: A case-control study was undertaken to compare operative outcomes for patients undergoing primary cytoreductive operations for ovarian cancer using two different operative strategies. Between 2002 and 2004, both stapling and conventional techniques were used to divide vascular pedicles for 50 consecutive patients requiring modified posterior exenterations (en-bloc resection of internal reproductive organs, pelvic peritoneum, and recto-sigmoid colon) and upper abdominal procedures in the context of primary cytoreduction for stage IIIC and IV ovarian cancer. The operative time, blood loss, transfusion rate, hospitalization, and incidence of complications were compared to outcomes of 50 consecutive patients operated on between 1994 and 1997 for whom stapling was not used to divide pedicles (chi-square test for binomial data, and t-test analysis for continuous data). RESULTS: Both groups were equivalent with respect to disease severity, extent of upper abdominal surgery, and cytoreductive outcomes. The group for whom stapling devises were used to divide pedicles had a significantly reduced total operative time 179 min vs. 284 min, P < 0.001), estimated blood loss (1170 ml vs. 1782 ml, P = 0.004), and transfusion rate (3.6 units packed red cells vs. 5.0 units packed red blood cells, P = 0.03). CONCLUSION: Stapling of vascular pedicles significantly reduces the operative time and blood loss for patients undergoing extensive primary cytoreductive operations for advanced ovarian cancer.

Laparoscopic modified radical hysterectomy: a strategy for a clinical dilemma.

OBJECTIVE: To investigate the role of laparoscopic modified radical (type 2) hysterectomy when cervical cancer cannot be excluded or documented preoperatively. METHODS: Between 1996 and 2004, 50 patients with cervical intraepithelial neoplasia (CIN III) or adenocarcinoma in situ (AIS) involvement of cone endocervical margins and/or endocervical curettings, who were not candidates for observation or repeat conization, underwent laparoscopy to perform a modified radical hysterectomy. RESULTS: Forty-nine (98.0%) modified radical hysterectomies were completed laparoscopically and one (2.0%) patient required a laparotomy. Of the overall group, 35 (70.0%) had residual pathology; 26 (52.0%) were precancerous lesions, and 9 (18.0%) had invasive disease (5 adenocarcinomas, 3 squamous lesions, and 1 adenosquamous carcinoma). Of the nine with cancer, one had stage IA1 disease, three had stage IA2 disease, and five had stage IB1 disease. Five (55.6%) invasive lesions were diagnosed intraoperatively (frozen section), and a laparoscopic pelvic and lower aortic lymph node dissection was performed. The median operative time was 96 min (range 58-185), blood loss 100 ml (50-450), and postoperative hospital stay 2.5 days (range 1-14). There were no incidences of prolonged urinary retention fistulas, or other serious complications. All patients with cancer remain disease-free (median follow-up 44.2 months, range 1-88.7 months). CONCLUSIONS: Laparoscopic modified radical hysterectomy is a treatment option for patients for whom cervical cancer cannot be definitively excluded, and can be completed with acceptable operative time, blood loss, and hospitalization.

Relative influences of tumor volume before surgery and the cytoreductive outcome on survival for patients with advanced ovarian cancer: a prospective study.

OBJECTIVE: The purpose of this study was to determine the relative influences of the extent of disease present before surgery and completeness of cytoreduction on survival for patients with advanced ovarian cancer. METHODS: Patients (408) with stage IIIC epithelial ovarian cancer had cytoreductive surgery before systemic platinum-based combination chemotherapy. A ranking system (0-3) was devised to prospectively quantify the extent of disease involving: (1) right upper quadrant (diaphragm/hepatic, and adjacent peritoneal surfaces), (2) left upper quadrant (omentum/gastro-colic ligament, spleen, stomach, transverse colon, splenic flexure of colon), (3) pelvis (reproductive organs, recto-sigmoid, pelvic peritoneum), (4) retroperitoneum (pelvic/aortic nodes), and (5) central abdomen (small bowel, ascending/descending colon, mesentery, anterior abdominal wall, pericolic gutters). Survival was analyzed (log rank and Cox regression) on the basis of the rankings at these anatomic regions, the sum of intraabdominal rankings, and the cytoreductive outcome. RESULTS: Overall median and estimated 5-year survivals were 58.2 months and 49%. On univariate analysis, the central abdominal (P = 0.008) and left upper quadrant (P = 0.03) rankings, the sum of rankings (P = 0.01), and the cytoreductive outcome (P 1 cm residual, RR 2.98; P = 0.001). CONCLUSIONS: Cytoreduction to a visibly disease-free outcome has a more significant influence on survival than the extent of metastatic disease present before surgery. Operative efforts should not be abbreviated on the hypothesis that extensive disease at specific anatomic regions precludes long-term survival.

Reduction of blood loss during extensive pelvic procedures by aortic clamping--a preliminary report.

OBJECTIVE: The aim was to determine the effect of intraoperative aortic clamping during extensive pelvic procedures on blood loss, operative time, and morbidity. METHODS AND MATERIALS: Thirteen women with ovarian cancer, 1 with cervical cancer, and 1 with an extensive pelvic sarcoma had their aortas completely occluded with a vascular clamp before the pelvic phases of their operations. Heparin and protamine reversal were used. RESULTS: Patients requiring en bloc excision of the internal reproductive organs, pelvic peritoneum, and recto-sigmoid colon in the context of a cytoreductive operation had a median estimated total blood loss of 650 ml (range 200 to 3500), a median of 2 units (range 0 to 8) of blood transfused, and a median total operative time of 155 min (range 90 to 280). There were no complications due to the aortic clamping. CONCLUSION: Most procedures were completed with a less than anticipated blood loss and operative time. Clamping of the aorta may potentially diminish blood loss, operative time, and the incidence of transfusion-related morbidity associated with extensive pelvic operations. Intraoperative aortic clamping merits further investigation.

Laparoscopic radical hysterectomy (type III) with aortic and pelvic lymphadenectomy in patients with stage I cervical cancer: surgical morbidity and intermediate follow-up.

OBJECTIVE: The purpose of this study was to determine the risk of recurrence and to quantify morbidity and mortality rates in patients with cervical cancer who consented to undergo laparoscopic radical hysterectomy (type III) and retroperitoneal lymphadenectomy. STUDY DESIGN: Seventy-eight consecutive patients with stage IA(2) and IB cervical cancer with at least 3 years of follow-up consented to undergo this surgical procedure with argon beam coagulation and endoscopic staplers. All patients had a Quetelet index of <35. The average age was 41.5 years (range, 26-62 years). Sixty-eight patients had squamous cell carcinomas; 8 patients had adenocarcinomas, and 2 patients had adenosquamous carcinomas of the cervix. RESULTS: All but 5 surgical procedures were completed laparoscopically. The average operative time was 205 minutes (range, 150-430 minutes). The average blood loss was 225 mL (range, 50-700 mL). One patient (1.3%) had transfusion. Operative cystotomies occurred for 3 patients: 2 cystotomies were repaired laparoscopically, and 1 cystotomy required laparotomy. One patient underwent laparotomy because of equipment failure, and another patient underwent laparotomy to pass a ureteral stent. Two other patients underwent laparotomy to control bleeding sites. The average lymph node count was 34 (range, 19-68). Nine patients (11.5%) had positive lymph nodes. All surgical margins were macroscopically negative, but 3 patients had microscopically positive and/or close surgical margins. One patient had a ureterovaginal fistula after the operation that required reoperation. Follow-up has been provided every 3 months. There have been 4 documented recurrences (5.1%), with a minimum of 3 years of follow-up. CONCLUSION: Laparoscopic radical hysterectomy (type III) can be successfully completed in patients with early-stage cervical cancer with acceptable morbidity. Intermediate-term follow-up validates the adequacy of this procedure.

Thoracoscopy for the management of advanced epithelial ovarian cancer--a preliminary report.

OBJECTIVE: To determine possible benefits of thoracoscopy for the management of patients with Stage IIIC and IV epithelial ovarian cancer. METHODS: Thirty patients underwent thoracoscopy at the time of primary cytoreduction to determine the presence and extent of intrathoracic disease and the feasibility of cytoreduction. Survival of patients with Stage IV disease undergoing thoracoscopy was compared to that of historical controls (Stage IV on the basis of positive pleural effusion cytology and/or pleural involvement by contiguous diaphragmatic metastases) who did not undergo thoracoscopy (log-rank analysis). RESULTS: Among the 24 patients with Stage IV disease having thoracoscopy, 11 (45.8%) did not have macroscopic intrathoracic disease, 10 (41.7%) underwent pleural implant ablation and/or excision as well as nodal excision that influenced the final cytoreductive outcome, and 3 (12.5%) had efforts to achieve complete intra-abdominal cytoreduction abbreviated after unresectable intrathoracic disease was found. The 24 patients who had thoracoscopy and the historical controls were not significantly different with respect to median age, performance status, extent of intra-abdominal disease, amount of ascites, and intra-abdominal cytoreductive outcome. The median and estimated 5-year survival for the entire cohort were 28.9 months and 42%, respectively. Log-rank analysis revealed the probability of survival to be improved by the performance of thoracoscopy (performed vs not performed, P = 0.05). CONCLUSIONS: Thoracoscopy quantifies the volume of intrathoracic disease, may allow abbreviation of the abdominal phase of cytoreduction for patients with unresectable pleural disease, and permits complete cytoreduction for some patients who might otherwise have unrecognized macroscopic residual intrathoracic disease. A multi-institutional prospective study may better define the role of this procedure in clinical practice.