Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.

OBJECTIVE: Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. METHODS: Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, ß = 80%, one sided. RESULTS: 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. CONCLUSION: The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.

The future for follow-up of gynaecological cancer in Europe. Summary of available data and overview of ongoing trials.

After completing treatment, most patients follow a pre-determined schedule of regular hospital outpatient appointments, which includes clinical examinations, consultations and routine tests. After several years of surveillance, patients are transferred back to primary care. However, there is limited evidence to support the effectiveness and efficiency of this approach. This paper examines the current rationale and evidence base for hospital-based follow-up after treatment for gynaecological cancer. We investigate what alternative models of care have been formally evaluated and what research is currently in progress in Europe, in order to make tentative recommendations for a model of follow-up. The evidence base for traditional hospital based follow-up is limited. Alternative models have been reported for other cancer types but there are few evaluations of alternative approaches for gynaecological cancers. We identified five ongoing European studies; four were focused on endometrial cancer patients and one feasibility study included all gynaecological cancers. Only one study had reached the reporting stage. Alternative models included nurse-led telephone follow-up and comparisons of more intensive versus less intensive regimes. Outcomes included survival, quality of life, psychological morbidity, patient satisfaction and cost effectiveness of service. More work is needed on alternative strategies for all gynaecological cancer types. New models will be likely to include risk stratification with early discharge from secondary care for early stage disease with fast track access to specialist services for suspected cancer recurrence or other problems.

Diagnostic accuracy and cost-effectiveness of different strategies to triage women with adnexal masses: a prospective study.

OBJECTIVE: Transvaginal sonography (TVS) and serum biomarkers are used widely in clinical practice to triage women with adnexal masses, but the effectiveness of current biomarkers is weak. The aim of this study was to determine the best method of diagnosing patients with adnexal masses, in terms of diagnostic accuracy and economic costs, among four triage strategies: (1) the International Ovarian Tumor Analysis group's simple rules (SR) for interpretation of TVS with subjective assessment (SA) by an experienced ultrasound operator when TVS results are inconclusive (referred to hereafter as SR ± SA), (2) SR ± SA and cancer antigen 125 (CA 125), (3) SR ± SA and human epididymis protein 4 (HE4) and (4) SR ± SA and the risk of malignancy algorithm (ROMA). Our main hypothesis was that the addition of the biomarkers to SR ± SA could improve triaging of these patients in terms of diagnostic accuracy (i.e. malignant vs benign). As secondary analyses, we estimated the cost effectiveness of the four strategies and the diagnostic accuracy of SR ± SA at the study hospitals. METHODS: Between February 2013 and January 2015, 447 consecutive patients who were scheduled for surgery for an adnexal mass at the S. Anna and Mauriziano Hospitals in Turin were enrolled in this multicenter prospective cohort study. Preoperative TVS was performed and preoperative CA 125 and HE4 levels were measured. Pathology reports were used to assess the diagnostic accuracy of the four triage strategies and the cost of each strategy was calculated. RESULTS: A total of 391 patients were included in the analysis: 57% (n = 221) were premenopausal and 43% (n = 170) were postmenopausal. The overall prevalence of malignancy was 21%. SR were conclusive in 89% of patients and thus did not require SA; the overall performance of SR ± SA showed a sensitivity of 82%, specificity of 92% and positive and negative predictive values and positive and negative likelihood ratios of 74%, 95%, 10.5 and 0.19, respectively. In premenopausal women, mean cost among the four triage strategies varied from €36.41 for SR ± SA to €70.12 for SR ± SA + ROMA. The addition of biomarkers to SR ± SA showed no diagnostic advantage compared with SR ± SA alone and was more costly. Among postmenopausal women, mean cost among the four triage strategies varied from €39.52 for SR ± SA to €73.23 for SR ± SA + ROMA. Among these women, SR ± SA + CA 125 and SR ± SA + ROMA had a higher sensitivity (both 92% (95% CI, 85-99%)) than SR ± SA (81% (95% CI, 71-91%)), but SR ± SA had a higher specificity (84% (95% CI, 77-91%)). SR ± SA + CA 125 and SR ± SA + ROMA improved diagnostic accuracy, each diagnosing a third more malignant adnexal masses. In postmenopausal women, compared with SR ± SA alone, SR ± SA + CA 125 showed a net reclassification improvement (NRI) of 28.8% at an extra cost of €13.00, while the extra cost for SR ± SA + ROMA was €33.71, with a comparable gain, in terms of NRI, as that of SR ± SA + CA 125. CONCLUSIONS: In our study sample, SR ± SA seems to be the best strategy to triage women with adnexal masses for surgical management. Among postmenopausal women, SR ± SA + CA 125 increased the NRI at a reasonable extra cost. Our data do not justify the use of HE4 and ROMA in the initial triage of women with adnexal masses. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

CO2 laser vaporization for the treatment of vaginal intraepithelial neoplasia: effectiveness and predictive factors for recurrence.

OBJECTIVE: To evaluate the outcome of vaginal intraepithelial neoplasia (VaIN) treatment with CO2 laser vaporization in terms of local recurrence and progression to vaginal carcinoma. Additionally, the authors investigated the predictive factors for first recurrence. MATERIALS AND METHODS: The medical records of all patients treated for VaIN with CO2 laser vaporization at Sant'Anna Hospital in Turin (1995-2012), were retrospectively reviewed. A univariate logistic model was applied to evaluate selected clinical features as predictive factors for recurrence. A multivariate logistic regression analysis was then carried out including significant risk factors after univariate analysis (p < 0.05). RESULTS: The analysis included 285 out of 302 patients. Seventy-one (25%) women relapsed; of these 24 VaIN 1 (22%), 37 VaIN 2 (27%), and ten VaIN 3 (26%). The median time to the first recurrence was 5.2 months (1.4-127.8) for VaIN 1, 6.6 months (1-85.2) for VaIN 2, and 3.6 months (1.2-62) for VaIN 3. Sixty-one out of 71 patients were retreated with CO2 laser vaporization. At the last follow-up visit, 273 (96%) women were free from VaIN. No patients progressed to vaginal carcinoma. The multivariate model showed a higher risk of VaIN recurrence in the case of previous hysterectomy (HR 3.3, 95% CI 1.7-6.3, p < 0.001) and concomitant H-SIL on the Pap smear (HR 1.9, 95% CI 1.2-3.1, p = 0.008). CONCLUSION: CO2 laser vaporization is an effective low impact treatment for VaIN. Despite this, VaIN recur, in particular in cases of previous hysterectomy and concomitant H-SIL on the Pap smear. An intensive follow-up is proposed for women with a high risk of VaIN relapse.

Clear cell endometrial cancer: a CTF multicentre Italian study.

UNLABELLED: Endometrial clear cell carcinoma (CCC) is a rare entity and only accounts for 1-6% of all endometrial cancers. CCC is considered an aggressive subtype of endometrial cancer with worse prognosis compared with type I cancer and more frequent relapses at distant and extrapelvic sites. These characteristics require specific treatment modalities, but rarity of the disease does not allow to identify evidence based indications for therapies. Objective of the present study is to analyse a series of cases treated in a multicentre Italian setting. MATERIALS AND METHODS: Sixty-five endometrial CCC were treated in the period 1990-2010 in the participating institutions. Slides of the pathological specimens were reviewed by a single pathologist of each institution and debatable cases were collegially reviewed. Clinical records were collected by a common database. Demographic, surgical pathological, and follow-up data were registered. Results: All patients received primary surgery. Stage of disease according FIGO 2009 was as follow: l a: 16.9%, lb: 35.4%, 2: 9.2%, 3a: 9.2%, 3b: 3.1%, 3c: 16.9%, 4a: 3.1%, and 4b: 6.1%. Adjuvant post-operative treatment was adopted in 53.8% of cases. A relapse was detected in 29.2% of cases with a majority of extrapelvic sites (68.4%). Five-year survival rate was significantly related to stage of disease with an excellent prognosis for Stage Ia e lb disease with a complete staging. In these cases adjuvant treatment does not show significant improvement of survival. Relapsed cases show a response rate to treatment in 26% of cases (predominantly chemotherapy). CONCLUSION: CCC requires extensive surgical staging. Stage I disease completely staged does not require adjuvant therapy. More advanced stages require adjuvant chemotherapy.

Adjuvant treatment and analysis of failures in patients with high-risk FIGO Stage Ib-II endometrial cancer: an Italian multicenter retrospective study (CTF study).

OBJECTIVES: The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion >50%, grade 2-3). METHODS: We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. RESULTS: Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p=0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). CONCLUSIONS: Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings.

Is there a role for postoperative treatment in patients with stage Ib2-IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study.

PURPOSE: Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. PATIENTS AND METHODS: This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p<0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p=0.0001). On multivariate analysis, consolidation therapy (p=0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p=0.0169) and consolidation therapy (p=0.0016) were independent prognostic variables for overall survival. CONCLUSION: Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment.

Pathological response on surgical samples is an independent prognostic variable for patients with Stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: an Italian multicenter retrospective study (CTF Study).

OBJECTIVES: The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. METHODS: This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. CONCLUSIONS: Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome.

The need for accredited training in gynaecological oncology: a report from the European Network of Young Gynaecological Oncologists (ENYGO).

BACKGROUND: Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbach's-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.

A search for predictive factors for hypersensitivity reactions to paclitaxel and platinum salts in chemotherapy for gynecologic pelvic neoplasms.

AIMS: To investigate the frequency of and predictive factors for hypersensitivity reactions (HR) to taxanes and platinum salts in a cohort of patients treated for pelvic gynecologic malignancies. METHODS: The medical records of all patients with gynecologic pelvic neoplasms treated with chemotherapy at the Department of Gynecologic Oncology, AO Mauriziano Umberto I of Turin, from September 2007 through August 2008, were retrospectively reviewed. Two multivariate models, regarding carboplatin and taxane chemotherapy, respectively, were performed to evaluate the potential predictive value of various clinical features. RESULTS: The incidence of HR was 14% (22/157). Multivariate models showed that menopausal women had a significantly lower probability of HR (OR 0.12, CI 0.02-1.13, p = 0.06 for the carboplatin model and OR 0.05, CI 0.01-0.63, p = 0.02 for the taxane model) while a history of systemic hypersensitivity was associated with a higher but non-significant risk of HR (OR 2.64, CI 0.78-8.95, p = 0.11, for the carboplatin model and OR 3.42, CI 0.94-12.45, p = 0.06, for the taxane model). CONCLUSION: We confirmed a history of hypersensitivity as a risk factor for HR. Other larger cohorts should be analyzed: we need to find new predictive factors in order to select women who should be submitted to experimental prophylactic strategies.

Prognostic value of lymph node status and number of removed nodes in patients with squamous cell carcinoma of the vulva treated with modified radical vulvectomy and inguinal-femoral lymphadenectomy.

PURPOSE OF INVESTIGATION: To assess the outcome of patients with squamous cell vulvar carcinoma treated with deep partial or total vulvectomy and inguinal-femoral lymphadenectomy. MATERIALS AND METHODS: The authors assessed 87 patients who underwent primary surgery. RESULTS: Tumor recurred in 34 patients, and the first relapse was local in 19, inguinal in ten, and distant in five. Five-year disease-free survival was 56.7% and was related to Stage (p < 0.0001), grade (p = 0.023), and node status (p < 0.0001). Groin failure occurred in 4.9% of node-negative patients compared with 29.6% of node-positive patients (p = 0.0096). Distant recurrences only developed in women with positive nodes. Among the 47 patients who underwent bilateral lymphadenectomy and who had negative nodes, groin recurrence occurred in 12% of those who had < or = 15 nodes removed and 0% of those who had > 15 nodes removed. CONCLUSIONS: Stage and node status were the most important prognostic variables. There was a trend favoring a better groin control in patients with node-negative disease who underwent extensive lymphadenectomy.

Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel.

BACKGROUND: Topotecan has single-agent activity in recurrent ovarian cancer. It was evaluated in a novel combination compared with standard frontline therapy. METHODS: Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer, Eastern Cooperative Oncology Group Performance Status of 1 or less, were stratified by type of primary surgery and residual disease, treatment center, and age; then randomly assigned to one of the two 21-day intravenous regimens. Patients in arm 1 (n = 409) were administered four cycles of cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1-5, then four cycles of paclitaxel 175 mg/m(2) over 3 hours on day 1 followed by carboplatin (area under the curve = 5) on day 1. Patients in arm 2 (n = 410) were given paclitaxel plus carboplatin as in arm 1 for eight cycles. We compared progression-free survival (PFS), overall survival, and cancer antigen-125 normalization rates in the two treatment arms. A stratified log-rank test was used to assess the primary endpoint, PFS. All statistical tests were two-sided. RESULTS: A total of 819 patients were randomly assigned. At baseline, the median age of the patients was 57 years (range = 28-78); 81% had received debulking surgery, and of these, 55% had less than 1 cm residual disease; 66% of patients were stage III and 388 (47.4%) patients had measurable disease. After a median follow-up of 43 months, 650 patients had disease progression or died without documented progression and 406 had died. Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 (hazard ratio = 1.10, 95% confidence interval = 0.94 to 1.28, P = .25). Among patients with elevated baseline cancer antigen-125, fewer in arm 1 than in arm 2 had levels return to normal by 3 months after random assignment (51.6% vs 63.3%, P = .007) CONCLUSIONS: Topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.

A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Urologic surgical procedures in patients with uterus neoplasm and colon-rectal cancer].

INTRODUCTION. During the last 30 years, the multidisciplinary treatments of colon and uterus neoplasm have yielded an increase in total survival rates, fostering therefore the increase of cases with regional relapse involving the urinary tract. In these cases the iterative surgery can be performed, if no disease secondary to pelvic pain, haemostatic or debulking procedure is present, and must be considered and discussed with the patient, according to his/her general status. MATERIALS AND METHODS. From 1997 to August 2007 we performed altogether 43 pelvic iterative surgeries, with simultaneous urologic surgical procedure because of pelvic tumor relapse in patients with uterus neoplasm and colon and rectal cancer. In 4 cases of anal cancer, the urological procedure were: one radical prostatectomy with continent vesicostomy in the first case, while in the other 3 cases radical pelvectomy with double-barrelled uretero-cutaneostomy. In 23 cases of colon cancer, the urologic procedures were: 9 cases of radical cystectomy with double-barrelled uretero-cutaneostomy, 4 cases of radical cystectomy with uretero-ileo-cutaneostomy according to Bricker- Wallace II procedure, and 9 cases of partial cystectomy with pelvic ureterectomy and ureterocystoneostomy according to Lich-Gregoire technique (7 cases) and Lembo-Boari (2 cases) procedure. In 16 cases of uterus cancer, the urological procedure were: 7 cases of partial cystectomy with pelvic ureterectomy and uretero-cystoneostomy according to Lich-Gregoire procedure; in 3 cases, a radical cystectomy with urinary continent cutaneous diversion according to the Ileal T-pouch procedure; 2 cases of total pelvectomy and double uretero-cutaneostomy, and 4 cases of bilateral uretero-cutaneostomy. RESULTS. No patients died in the perioperative time; early systemic complications were: 2 esophageal candidiasis, 1 case of venous thrombosis. CONCLUSIONS. The iterative pelvic surgery in the case of oncological relapse involving the urinary tract aims to achieve the best quality of life with the utmost oncological radicality. The equation: eradication of pelvic neoplasm and urinary tract reconstruction, with acceptable quality of life, will be the future target; nevertheless, it is not possible to establish guidelines beforehand, and the therapy must be adapted to each single case.

Classification of radical hysterectomy adopted by the Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer.

The Piver classification of radical hysterectomy for the treatment of cervical cancer is outdated and misused. The Surgery Committee of the Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer (EORTC) produced, approved, and adopted a revised classification. It is hoped that at least within the EORTC participating centers, a standardization of procedures is achieved. The clinical indications of the new classification are discussed.

Could follow-up different modalities play a role in asymptomatic cervical cancer relapses diagnosis? An Italian multicenter retrospective analysis.

OBJECTIVE: The aim of this study was to evaluate how much clinical surveillance performed by follow-up scheduled appointments may correctly identify asymptomatic recurrences and describe the pattern of relapse detected by procedures. METHODS: The records of 327 consecutive women with recurrent cervical cancer treated from 1980 to 2005 were retrospectively collected in 8 Italian Institutions. Primary disease and recurrence data were picked up: diagnosis, type of treatment, FIGO stage, tumour grade, histology, clinical lesion size, number of localizations and site of relapse, presence of symptoms and primary method of detection, the type of treatment of recurrence and follow-up data, such as appointment date, clinical status and procedure performed. A multivariate analysis was carried out using the Cox proportional hazards regression model. Survival curves were calculated using the Kaplan-Meier technique. Survival differences were evaluated by the log-rank test. RESULTS: Sixty-seven out of 327 patients (20.5%) had a local recurrence on vaginal vault, 120 (36.7%) in central pelvis, 31 (9.5%) in pelvic wall, 16 cases (4.9%) in lymph nodes. Seventy-nine patients (24.2%) showed a distant relapse while 14 (4.3%) developed both a distant and local relapse. Among patients with distant relapses 39 (49.4%) had lung metastasis, 41 (51.9%) an hepatic recurrence, 4 (5.1%) a bone relapse. Among distant sites 32 out of 79 patients (40.5%) had single relapse and 46 (58.2%) had multiple localizations. The site of relapse influenced survival since patients with vaginal vault recurrences lived significantly longer than patients with recurrences in other sites. Ninety-seven (29.7%) patients were symptomatic and anticipated the scheduled visit, 66 (20.2%) reported their symptoms during the follow-up visit and 164 (50.1%) were asymptomatic and the diagnostic path was introduced by a planned visit or exam. Between asymptomatic patients the first procedure was clinical visit for 85 patients out of 164 patients (51.8%), imaging for 60 patients (36.6%), both clinical visit and imaging for 14 (8.5%) and cytology for 5 (3%, Pap smear test). The median OS of symptomatic patients was 37 months versus 109 months of asymptomatic patients (Log rank, p=0.00001). The median survival since recurrence was 9 months for symptomatic patients and median was not reached for asymptomatic patients (p<0.0001). The median disease-free interval was 24 months for asymptomatic patients vs. 36 months for symptomatic patients (p=0.03). CONCLUSIONS: Our study helps demonstrate the great need of prospective cost-effectiveness studies which are lacking at the present time.

Follow-up strategies in gynecological oncology: searching appropriateness.

Nowadays, the cost for oncology diseases is growing rapidly, in particular as a consequence of the introduction of new drugs and new diagnostic procedures, and becoming a considerable percentage of the global healthcare expense. On the other hand, a substantial amount of that cost is considered to be imputable to the follow-up procedures. The aim of our paper is to introduce the debate about follow-up policies adopted in gynecological oncology throughout a literature review just based on cost-effectiveness and cost-efficacy in order to explore if the data are consistent with evidences available in this field. Furthermore, it is discussed if common practice fits the needs of patients, gynecological oncologists, and health service. Despite the fact that in gynecological oncology we must consider different clinical situations concerning each specific neoplasm with their peculiar natural history, some general considerations could be drawn in order to set up future initiatives properly.

Ovarian metastases in early-stage cervical cancer (IA2-IIA): a multicenter retrospective study of 1965 patients (a Cooperative Task Force study).

This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (45 years: P = 0.0079), FIGO stage (IB1-IIA 4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.

Surveillance procedures for patients treated for epithelial ovarian cancer: a review of the literature.

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in the Western countries. Approximately 20%-30% of patients with early-stage disease and 50%-75% of those with advanced disease who obtain a complete response following first-line chemotherapy will ultimately develop recurrent disease, which more frequently involves the pelvis and abdomen. Few formal guidelines exist regarding the surveillance of these patients, and there is no agreement in the literature about the type and timing of examinations to perform. Moreover, the objective of follow-up is unclear as recurrent epithelial ovarian cancer continues to be a therapeutic dilemma and quite all the relapsed patients will eventually die of their disease. The follow-up of asymptomatic patients generally include complete clinical history, serum cancer antigen (CA)125 assay, physical examination, and often ultrasound examination, whereas additional radiologic imaging techniques are usually performed when symptoms or signs appear. (18)Fluoro-2-deoxy-glucose ((18)FDG)-positron emission tomography (PET) has a sensitivity of 90% and a specificity of 85% approximately for the detection of recurrent disease, and this examination appears to be particularly useful for the diagnosis of recurrence when CA125 levels are rising and conventional imaging is inconclusive or negative. Recently, technologic advances have led to novel combined (18)FDG-PET/computed tomography (CT) devices, which perform contemporaneous acquisition of both (18)FDG-PET and CT images. The role of (18)FDG-PET/CT for the detection of recurrent ovarian cancer is very promising, and this technique may be especially useful for the selection of patients with late recurrent disease who may benefit from secondary cytoreductive surgery.