Treatment of ("bulky") stage IB cervical cancer with or without neoadjuvant vincristine and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: a phase III trial of the gynecologic oncology group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study. The role of neoadjuvant chemotherapy for squamous cell cervical cancer (Ib-IIIb): a long-term randomized trial. Prognostic factors of stage IV epithelial ovarian cancer: a multicenter retrospective study. Stages III and IV invasive epithelial ovarian carcinoma in younger versus older women: what prognostic factors are important? Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Identification of prognostic factors in advanced epithelial ovarian carcinoma. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. Survival in ovarian cancer in Wales: Prior to introduction of all Wales guidelines. Aggressive surgical effort and improved survival in advanced-stage ovarian cancer.
A randomized phase III trial was conducted to determine if neoadjuvant chemotherapy (NACT) prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy (RHPPL) could improve progression-free survival (PFS) and overall survival (OS), as well as operability, with acceptable levels of toxicity. Adjuvant radiation therapy was prescribed for specific surgical/pathological risk factors for both regimens.
                Eligible patients were required to have bulky FIGO Stage IB cervical cancer, tumor diameter > or =4 cm, adequate bone marrow, renal and hepatic function, and performance status < or =2. Prospective random allocation was to either NACT (vincristine-cisplatin chemotherapy every 10 days for 3 cycles) before exploratory laparotomy and planned RHPPL (NACT+RHPPL), or RHPPL only.
                The study was closed prematurely, because of slow accrual, after 291 patients were enrolled, three were ineligible; thus 288 were eligible and randomly allocated to RHPPL (N=143) or NACT+RHPPL (N=145). There were no notable differences between regimens with regard to patient age, race, performance status, or tumor size. The median follow-up time is 62 months among living patients. The NACT+RHPPL group had very similar recurrence rates (relative risk: 0.998) and death rates (relative risk: 1.008) when compared to the RHPPL group. There were 79% that had surgery in the RHPPL group compared to 78% in the NACT RHPPL group. There were 52% who received post op RT in the RHPPL group compared to 45% in the NACT+RHPPL group (not statistically significant).
                There is no evidence from this trial that NACT offered any additional objective benefit to patients undergoing RHPPL for suboptimal Stage IB cervical cancer. Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer.
                We randomly assigned patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery).
                Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval [CI], 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival.
                Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.) Despite correlation between the completeness of surgical cytoreduction and survival for patients with advanced ovarian cancer, relatively few undergo complete cytoreduction. This study was initiated to prospectively determine the ability to surgically eliminate all visible disease in patients with stage IIIC and IV epithelial ovarian cancer and the associated impact on survival.
                Between 1990 and 1996, 163 consecutive patients underwent primary cytoreduction. The goal was the excision or ablation of all visible disease prior to initiation of systemic platinum-based combination chemotherapy. A multivariate analysis determined which clinical and pathologic variables influenced the probability of achieving complete cytoreduction (logistic regression) and survival (Cox proportional hazards model).
                One hundred thirty-nine patients (85.3%) underwent removal of all visible tumor, 22 (13.5%) had cytoreduction to </=1 cm residual disease, and 2 (1.2%) had unresected bulky disease. The median and estimated 5-year survival for the entire cohort was 54 months and 48%, respectively. The probability of achieving complete cytoreduction was influenced independently by the preoperative Gynecologic Oncology Group performance status (0-1 vs 2-3, P = 0.04), the number of mesenteric and intestinal serosal implants (</=75 vs >75 implants, P = 0.005), and stage (IIIC vs IV, P = 0.006). The probability of survival was independently influenced by age (</=61 vs >61 years, P = 0.003), volume of ascites (</=1 vs >1 liter, P = 0.01), stage (IIIC vs IV, P = 0.04), histology (clear cell and mucinous vs all other, P = 0.03), and the completeness of cytoreductive operation (complete vs incomplete cytoreduction, P = 0.02).
                Complete cytoreduction is possible for the majority of patients and improves survival, even compared to operations with minimal (</=1 cm) residual disease. Unless their medical condition prohibits anesthesia and surgery, patients with advanced epithelial ovarian cancer should undergo primary cytoreductive surgery with the intention of complete tumor removal.
                Copyright 1998 Academic Press. to verify whether a regimen of preventive chemotherapy in the treatment of cervical carcinoma allows surgical treatment in a larger number of patients and whether cases treated with this combined neoadjuvant polychemotherapy/surgery regimen improves overall and disease-free survival rates. Design: prospective randomized clinical study. Setting: Department of Gynaecology and Obstetrics, University of Rome "La Sapienza".
                192 patients suffering from squamous cell carcinoma of the uterine cervix in Stages Ib-IIb were randomized to one of the following treatments: three courses of neoadjuvant chemotherapy with cisplatin, vincristine, bleomycin (NACT arm; n = 106); conventional surgery or radiotherapy alone (CO arm; n = 86). One hundred and fifty-six patients in Stage Ib-IIb (n = 86, NACT arm and n = 70, CO arm) and 16 patients in Stage III (NACT arm) who proved to be sensitive to the neoadjuvant chemotherapy, underwent radical hysterectomy. Four Stage III patients not sensitive to chemotherapy and 16 patients, Stage III, of the CO arm underwent radiotherapy.
                the 5-year overall survival rates for the NACT and CO arm, respectively, were 78.6% and 73.2% in Stages Ib-IIa (p = NS), 68.7% and 64.3% in Stage IIb (p = NS). A 5-year disease-free survival rate for the NACT arm and CO arm, respectively, of 77.1% and 64.3% in Stages Ib-IIa (p < .05), 56.2% and 57.1% in Stage IIb (p = NS) was found.
                the responsiveness of cervical cancer to neoadjuvant chemotherapy allows surgical treatment in a larger number of patients and results in longer overall and disease-free survival. In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer.
                In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods.
                Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415).
                Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.
                Copyright 2001 Academic Press. OBJECTIVE; To compare the survival rates in younger (45 years or younger) and older women (over 45) diagnosed with advanced-stage invasive epithelial ovarian cancer. Clinical and pathologic factors responsible for survival differences between the two groups were also determined.
                All younger women with advanced-stage epithelial ovarian carcinoma diagnosed between 1984 and 2001 were identified from tumor registry databases at two hospitals. Patients with borderline tumors were excluded. An older group of comparable controls was selected for comparison. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival.
                Of 104 women with advanced-stage epithelial ovarian carcinoma, 52 were 45 or younger and the rest were over 45. The 5-year survival rate and median survival in younger patients were 48% and 54 months, compared with 22% and 34 months in the older women (P =.003). Younger women had significantly better performance status than older patients, and survival remained significantly better in younger women based on Kaplan-Meier analysis stratified by performance status (0 versus 1 to 2, P =.02). Furthermore, overall survival was significantly better in younger women after stratification by stage (III versus IV, P =.002) and by cytoreductive surgery (optimal versus suboptimal, P =.003). Multivariable analysis demonstrated that all these factors remained as significant independent prognostic factors for survival.
                Younger women with advanced-stage invasive epithelial ovarian cancer have significantly improved survival rates relative to older patients. Age, performance status, stage of disease, and extent of cytoreductive surgery are important independent prognostic factors for survival. The role of cytoreductive surgery in relapsed ovarian cancer is not clearly defined. Therefore, patient selection remains arbitrary and depends on the center's preference rather than on established selection criteria. The Descriptive Evaluation of preoperative Selection KriTeria for OPerability in recurrent OVARian cancer (DESKTOP OVAR) trial was undertaken to form a hypothesis for a panel of criteria for selecting patients who might benefit from surgery in relapsed ovarian cancer.
                The DESKTOP trial was an exploratory study based on data from a retrospective analysis of hospital records. Twenty-five member institutions of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Committee (AGO OC) and AGO-OVAR boards collected data on their patients with cytoreductive surgery for relapsed invasive epithelial ovarian cancer performed in 2000-2003.
                Two hundred and sixty-seven patients were included. Complete resection was associated with significantly longer survival compared with surgery leaving any postoperative residuals [median 45.2 vs. 19.7 months; hazard ratio (HR) 3.71; 95% confidence interval (CI) 2.27-6.05; P < .0001]. Variables associated with complete resection were performance status (PS) [Eastern Cooperative Oncology Group (ECOG) 0 vs. > 0; P < .001], International Federation of Gynecology and Obstetrics (FIGO) stage at initial diagnosis (FIGO I/II vs. III/IV, P = .036), residual tumor after primary surgery (none vs. present, P <.001), and absence of ascites > 500 ml (P < .001). A combination of PS, early FIGO stage initially or no residual tumor after first surgery, and absence of ascites could predict complete resection in 79% of patients.
                Only complete resection was associated with prolonged survival in recurrent ovarian cancer. The identified criteria panel will be verified in a prospective trial (AGO-DESKTOP II) evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in recurrent ovarian cancer. The Gynecologic Oncology Group (GOG) has demonstrated that age, tumor grade, and size and number of residual lesions after primary cytoreductive surgery are significant prognostic factors in advanced ovarian carcinoma. Recent studies have reported numerous other clinical features as having prognostic value. We sought to identify the independent prognostic factors for survival in a cohort of patients with advanced ovarian cancer.
                We performed a retrospective chart review of all patients with stage III and IV ovarian carcinoma who received their primary treatment at our institution between 1987 and 1994.
                A total of 295 patients were identified, 282 of whom were evaluable. Of these 282 patients, 214 (76%) have died of disease or other causes. The median follow-up is 32 months (range: 1-139). Eighteen factors were evaluated for prognostic significance. Significant factors in univariate analysis included patient age, gravidity (0 vs > 0), parity (0 vs > 0), preoperative albumin level, preoperative total protein level, ascites (presence vs absence), disease stage (IIIA/IIIB vs IIIC vs IV), number of residual lesions (< or =20 vs >20), and diameter of largest residual tumor nodule (< or = 1 cm vs 1-2 cm vs > 2 cm). However, on multivariate analysis, only patient age (P < 0.001), ascites (P = 0.001), and size of residual disease (P = 0.005) retained prognostic significance. Substage of disease was of borderline significance (P = 0.086).
                Although numerous clinical variables have recently been reported to have prognostic value in advanced ovarian carcinoma, only patient age, presence or absence of ascites, and diameter of the largest residual tumor nodule proved to be of statistical significance in our analysis.
                Copyright 2001 Academic Press. Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity.
                Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B).
                Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P =.007 and P =.02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P =.005 andP =.02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P =.36 and P =.29), respectively. Treatment had a significant impact on OS and PFS.
                Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT. The objective of the study was to review referral practice, overall management, and survival in women with suspected ovarian cancer in Wales. This study was done prior to introduction of cancer management guidelines in the region. A confidential study questionnaire was sent to 20 participating hospitals. Data on 287 consecutive women with suspected ovarian cancer were collected, of which 250 women underwent primary laparotomy. Information was obtained on referral pattern, preoperative investigations, place of primary surgery, specialty of the primary surgeon, surgical parameters recorded at the time of operation, a final overall stage, adjuvant treatment, and survival outcome. There was a wide variation in referral practice and management of ovarian cancer in Wales. Stage of the disease, attempt at optimal debulking, residual disease, management by a cancer centre multidisciplinary team, and platinum-based chemotherapy were associated with improved overall survival and progression-free survival. More women were alive if managed in the cancer centre at 1 and 3 year after diagnosis (P = 0.022). This study has highlighted the acute issue of the standards of clinical care in the area of ovarian cancer management and will emphasize the implementation of better care pathways for ovarian cancers. Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival.
                A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival.
                The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001).
                Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis.
                II-2.
We consider the use of NACT in women with stage IIIc/IV ovarian cancer to be a reasonable alternative to PDS, particularly in bulky disease. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account resectability, age, histology, stage and performance status. These results cannot be generalised to women with stage IIIa and IIIb ovarian cancer; in these women, PDS is the standard. We await the results of three ongoing trials, which may change these conclusions.