[show abstract][hide abstract] ABSTRACT: The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer.In the attempt to identify the patients with poorer prognosis,the impact of age and body mass index were also thoroughly investigated by cancer specific survival analyses.
Survival outcomes of trial patients were analysed in relation to age(<65 years and >65 years) in the two arms(lymphadenectomy and no lymphadenectomy) and in the whole population of the trial.
Univariate and multivariable analyses of CSS and OS of patients showed that age >65 years is a strong independent poor prognostic factor(5-yr OS 92.1% and 78.4% in <65 years and >65 yr patients respectively,P<0.0001;5-yr CSS 93.8% and 83.5% in <65 years and >65 years patients respectively,P=0.003).Among women < 65 yr, node negative patients had 94.4% 5yr OS and 96.3% 5yr CSS vs 74.3% 5yr OS and 74.3% 5yr CSS for node positive patients(P=0.009 and P=0.002,respectively),while among women >65 yr, node negative patients had 75.7% 5yr OS and 83.6% 5yr CSS vs 74.1% 5yr OS and 83.3% 5yr CSS for node positive patients(P=0.55 and P=0.58,respectively).Univariate and multivariable survival analyses in the whole trial population showed that older age,higher tumor grade and stage were significantly associated to a worse prognosis.
Elderly women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy,and,unexpectedly,irrespective of the presence of nodal metastasis.Only in elderly patients obesity (BMI > 30) was significantly associated with scarce prognosis.
American journal of obstetrics and gynecology 12/2013; · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies.
From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA-IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS).
The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87-1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for death=1.04, 95% CI=0.733-1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively).
SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS.
British Journal of Cancer 08/2012; 107(5):785-92. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: In circa 2 anni di lavoro una commissione di esperti, no-minati dalle rispettive società scientifiche italiane, ha riesa-minato la letteratura medica ed ha elaborato una serie di rac-comandazioni in materia di impiego della diagnostica per immagini nelle disfunzioni del pavimento pelvico. Sono sta-ti individuati (A) i tipi di indagine utili e (B) le condizioni cliniche in cui è dimostrata l'efficacia sulla gestione del pa-ziente. Il documento fornisce ai potenziali utilizzatori la ne-cessaria cornice normativa e fissa gli standard dei requisiti (attrezzature, livello di competenza dell'operatore, procedu-ra) indispensabili per l'impiego dei vari esami e suggerisce quale sia l'indagine più appropriata per la soluzione del pro-blema clinico specifico, indicando i rispettivi livelli di evi-denza e la forza delle raccomandazioni. IMPLEMENTAZIONE DI LINEE GUIDA PER L'IMAGING Il presente documento si ripropone di definire il ruolo del-l'imaging diagnostico nelle disfunzioni del pavimento pelvi-co, prendendone in considerazione gli aspetti fondamentali: (1) la giustificazione dell'esame (appropriatezza); e (2) la tutela della qualità del prodotto (requisiti). Questa iniziativa risponde alla necessità di razionalizzare e rendere utilizzabili per le decisioni cliniche la grande quantità di nuove conoscenze prodotte in campo medico e biologico nel settore della diagnostica per immagini, e di di-sporre di strumenti che, attraverso la medicina basata sulla evidenza (EBM), siano in grado di migliorare l'efficacia de-gli interventi per un uso più razionale delle risorse.
[show abstract][hide abstract] ABSTRACT: Five percent to 20% of stage I endometrial cancer patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy develop vaginal and pelvic recurrences. Adjuvant radiotherapy can improve locoregional control but not survival. This randomized trial aimed to determine whether a modified radical (Piver-Rutledge class II) hysterectomy can improve survival and locoregional control compared to the standard extrafascial (Piver-Rutledge class I) hysterectomy.
Eligible patients (n = 520) with stage I endometrial cancer were randomized to class I or class II hysterectomy. Primary endpoint was overall survival.
The median length of parametria and vagina removed were 15 and 5 vs. 20 mm and 15 mm for class I and class II hysterectomy, respectively (P > 0.001). Operating time and blood loss were statistically significantly higher for class II hysterectomy. At a median follow-up of 70 months, 51 patients had died. Five-year disease-free and overall survival were similar between arms (87.7 and 88.9% in the class I arm and 89.7 and 92.2% in the class II arm, respectively). The unadjusted hazard ratios for recurrence was 0.91 (95% confidence interval, 0.55-1.51, P = 0.72), and the hazard ratio for death was 0.77 (95% confidence interval, 0.44-1.33, P = 0.35).
Class II hysterectomy did not improve locoregional control and survival compared to class I hysterectomy, but when an adequate vaginal cuff transection is not feasible with class I hysterectomy, a modified radical hysterectomy allows to obtain an optimal vaginal and pelvic control of disease with a minimal increase in surgical morbidity.
Annals of Surgical Oncology 10/2009; 16(12):3431-41. · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control.
In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response.
Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP.
TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.
Annals of Oncology 01/2009; 20(4):660-5. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival.
From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided.
The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively).
Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.
[show abstract][hide abstract] ABSTRACT: No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.
British Journal of Cancer 09/2006; 95(6):699-704. · 5.08 Impact Factor