Negative Para-aortic Nodes Research Articles

Para-aortic Lymph Node Dissection for Women With Endometrial Adenocarcinoma and Intermediate- to High-Risk Tumors: Does It Improve Survival?

Literature suggests that para-aortic lymphadenectomy (para-aortic lymph node dissection [PALND]) has a therapeutic benefit for women with intermediate- to high-risk endometrial adenocarcinoma. We hypothesized that the observed survival advantage of PALND is a reflection of the general health of the patient rather than a therapeutic benefit of surgery. Women with intermediate- to high-risk endometrial adenocarcinoma diagnosed from 2002 to 2009 at a single institution were identified. Medical comorbidities, pathology, and survival information were abstracted from the medical record. The χ test or the t test was used for univariate analysis. Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. A total of 253 women with a mean age of 64 years were identified. Of these women, 174 had a pelvic lymphadenectomy (pelvic lymph node dissection [PLND]) and 82 had PLND and PALND. The rate of positive nodes was 13% (23/174) for the women who had PLND and was 7% (6/82) for those who had PLND and PALND. Only 1.2% (1/82) of the women who had PLND and PALND had negative pelvic but positive para-aortic nodes. The patients who had PALND had a lower body mass index and were less likely to have significant medical comorbidities. The patients who had PALND had improved 5-year OS (96% vs 82%, P = 0.007) but no difference in 5-year DSS (96% vs 89%, P value = not significant). Women with intermediate- to high-risk endometrial adenocarcinoma who undergo PALND have improved OS but no improvement in DSS. The lack of difference in DSS supports the hypothesis that underlying comorbidities as opposed to lack of PALND result in poorer outcome.

Five-year outcome of concurrent radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer: single-institution experience

BACKGROUND AND OBJECTIVESWe aimed to evaluate long-term treatment outcomes and toxicity profile of combined radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer.DESIGN AND SETTINGSRetrospective study in a tertiary care cancer center in Riyadh, Saudi Arabia.METHODS AND MATERIALSThe medical records of patients with histopathologically proven, locally advanced cervical cancer were analyzed. These patients received three-dimensional conformal radiotherapy with concurrent chemotherapy followed by high dose rate brachytherapy in our center between July 2007 and April 2012. The data regarding the safety profile, response rates, occurrence of locoregional or distant failure, disease-free survival, and overall survival rates were recorded.RESULTSThe median follow-up period was 60 months (range, 8–66) for 74 patients. The median age of study population was 52.3 years (32–78), and the stage IIB was the predominant stage (49 patients [66.2%]). A total of 45 patients (60.9%) had radiologic-positive pelvic ± para-aortic lymphadenopathy. The 5-year locoregional and distant control rates were 84.3% and 78.5%, respectively. The 5-year disease-free and overall survival rates were 75.7% and 64.5%, respectively. Stage, nodal status, and hemoglobin levels were found to be important prognostic factors for locoregional and distant control. Acute grade 3 hematological and nonhematological toxicities were seen in 4 (5.4%) and 4 (5.4%) patients. Late toxicities were mild, and only 1 (1.4%) patient presented with subacute intestinal obstruction.CONCLUSIONConcurrent chemoradiation in Saudi women with locally advanced cervical cancer showed better locoregional and distant control and survival rates with minimal toxicity.

PD-0606: Extended field chemoradiation for radiologic negative para-aortic lymph nodes locally advanced cervical cancer

PD-0606: Extended field chemoradiation for radiologic negative para-aortic lymph nodes locally advanced cervical cancer

Clinical analysis on the lymph nodes metastasis characters and their relation with the prognosis of the endometrial carcinoma patients

To explore the lymph nodes (LN) metastasis characters of the endometrial carcinoma and its relation with the patients' prognosis. A retrospective study was carried out on 227 cases of endometrial carcinoma who admitted to our department and underwent LN excision from Jul.2000 to Feb.2008. Among 227 cases who underwent pelvic LN excision, there were 22 cases (9.7%) presented LN metastasis. There were 12 cases with positive external iliac LN from 20 cases of patients with data in LN grouping. Para-aortic LN excision was carried out on 138 patients. There were 6 cases with positive para-aortic LN, 5 cases of them together with pelvic LN metastasis. Those patients with cervix involvement, annex metastasis, deep myometrium infiltration, grade 2-3 and negative estrogen receptor occurred pelvic LN metastasis more frequently than the others (P < 0.05). Among the 6 cases with positive para-aortic LN, there were 3 cases (3/6) with deep myometrium infiltration. For those whose para-aortic LN was negative, it was only 16.7% (22 cases). But there were no difference statistically between them (P > 0.05). There were significant difference in 3 years disease-free survival rate between patients with positive pelvic LN or negative pelvic LN [(81.8 ± 8.2)% vs (97.4 ± 1.2)%, P = 0.004]. While there were not significant difference in 3 years disease-free survival rate between patients with positive para-aortic LN or negative para-aortic LN [100% vs (96.7 ± 1.6)%, P > 0.05]. Single factor analysis showed that the age more than 50 years, annex metastasis and pelvic LN metastasis related with the recurrence (P < 0.01). But cervix involvement, deep myometrium infiltration, para-aortic LN metastasis, pathology type, tumor grade and estrogen receptor did not relate with the recurrence (P > 0.05). Cox regression analysis showed that annex metastasis and the age of patients were independent risk factors affecting the recurrence (P = 0.011, P = 0.025). The most common site of pelvic LN metastasis is the external iliac LN for endometrial carcinoma patients. The patients with positive para-aortic LN always accompanied pelvic LN metastasis. Those patients with cervical involvement, annex metastasis, deep myometrium infiltration, poor differentiation and negative estrogen receptor be more likely exist pelvic LN metastasis. Pelvic LN metastasis may affect the prognosis of endometrial carcinoma patients.

Is Para‐aortic Lymph Node Metastasis a Contraindication for Radical Resection in Biliary Carcinoma?

Para-aortic nodal dissection in patients with biliary carcinoma has not been performed routinely worldwide. Therefore, the prognostic impact of para-aortic lymph node metastasis in biliary carcinoma has not yet been evaluated. The aim of this study was to clarify the prognostic impact of para-aortic lymph node metastasis in biliary carcinoma. Of 113 patients with biliary adenocarcinoma who underwent surgical resection with regional and para-aortic lymph node dissection, para-aortic lymph node metastasis was found in 17 patients (15%) by final pathological examination. Relationships between clinicopathological factors, including para-aortic lymph node metastasis, and survival were analyzed by univariate and multivariate analyses. Overall survival rates for the 113 patients were 82% at 1 year, 65% at 2 years, 58% at 3 years, and 52% at 5 years. Univariate analysis revealed that better tumor differentiation (P=0.044), negative lymph node metastasis (P<0.001), negative para-aortic lymph node metastasis (P=0.007), negative surgical margin status (P<0.001), lower UICC pT factor (P=0.009), and earlier UICC stage (P<0.001) were associated significantly with longer survival. Lymph node metastasis (P=0.004) but not para-aortic lymph node metastasis (P=0.323) remained associated independently with longer survival by multivariate analysis. Five-year survival rates for node-negative patients, node-positive patients without para-aortic lymph node metastasis, and node-positive patients with para-aortic lymph node metastasis were 72, 31, and 24%, respectively. Radical resection should not be abandoned for patients with para-aortic lymph node metastasis in biliary adenocarcinoma.

Pretherapeutic Extraperitoneal Laparoscopic Staging of Bulky or Locally Advanced Cervical Cancer

To assess the safety, feasibility, and impact on survival of extraperitoneal para-aortic lymphadenectomy in the staging of patients with bulky or locally advanced cervical cancer. Between August 2001 and October 2009, 87 consecutive patients (median age 5 years) with bulky or locally advanced cervical cancer underwent extraperitoneal laparoscopic infrarenal aortic and common iliac dissection as a pretherapeutic staging procedure. Data on pathologic findings, details of surgery, postoperative complications, and disease status at follow-up were collected. The median operating time was 150 min (range 60-255 min). The mean (± standard deviation) para-aortic nodal yield was 15.5 ± 8.1 (range 4-62). In none of the patients, conversion to the transperitoneal approach or laparotomy was necessary. Histological examination revealed metastasis in 13 patients (macroscopic disease 10, microscopic disease 3). After a median follow-up of 33.4 months (range 13.3-65.9 months), 73.6% of patients were free of disease and 1.1% were alive with disease, 19.5% died from cervical cancer, and 3.3% died from other causes. After a follow-up of 3 years, no deaths or recurrences were documented, with an overall survival rate of 74.8% (95% CI 62.8%-83.4%) and disease-free survival of 86% (95% CI 74.7%-92.5%). There were no significant differences in overall survival and disease-free survival between patients with positive and negative para-aortic lymph nodes. The extraperitoneal laparoscopic para-aortic lymphadenectomy for pretherapeutic surgical staging in cervical cancer is a safe and feasible procedure that should be considered as a tool to identify lymph node positive patients who require extended-field radiation and/or chemotherapy.

Incidence of micrometastases in histologically negative para-aortic lymph nodes in advanced cervical cancer patients

Objective Aims of the study were to identify the incidence of micrometastases in negative para-aortic lymph nodes, and to assess the utility of ultrastaging in histologic evaluation of para-aortic lymph nodes. Material and methods Patients with advanced cervical cancer and negative para-aortic lymph nodes after routine histology examination were included. Paraffin-embedded tissue blocks were cut into 5-μm-thick slides at step serial sections at 200-μm intervals until there was no lymph node tissue left. 7 to 14 slides were obtained per lymph node and an immunohistochemistry staining with anti-cytokeratin antibody (EA1/EA3) was performed. Results 581 histologically negative aortic nodes of 24 patients with advanced cervical cancer were assessed for para-aortic micrometastases (PAM). The incidence of micrometastases by the total number of studied lymph nodes was 0.003%. PAM were identified in 2 patients (8.3%), and additional submicrometastases were also found in one of them (4.1%). A single metastatic cluster of less than 0.2 mm was found in an afferent lymphatic vessel of another patient, not considered as a submicrometastases. PAM incidence was too low to allow for evaluation of associated risk factors, and for analysis of prognostic significance. Conclusion Although examination of PAM with ultrastaging and IHC is expensive and time-consuming, and difficult to be routinely applied to all negative lymph nodes retrieved in a para-aortic lymphadenectomy, this study adds to current evidence that removal of aortic nodes may benefit a subgroup of advanced cervical cancer patients with PAM and negative aortic lymph node at imaging techniques including PET-scan.

Long-Term Survival in Patients With Para-Aortic Lymph Node Metastasis With Systematic Retroperitoneal Lymphadenectomy Followed by Adjuvant Chemotherapy in Endometrial Carcinoma

The purposes of this study were to assess modified radical hysterectomy including systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node (PAN) metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for long-term survival during the past 10 years. Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy and peritoneal cytology in 284 endometrial carcinoma patients according to the classification of the International Federation of Gynecology and Obstetrics (stage IA, n = 66; stage IB, n = 96; stage IC, n = 33; stage IIA, n = 5; stage IIB, n = 20; stage IIIA, n = 28; stage IIIC, n = 28; and stage IV, n = 8) who gave informed consents at our institute. Patients with tumor confined to the uterus (stages IC and II) were treated by 3 courses of cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, and cisplatin 75 mg/m2 regimen 3 to 4 weeks apart, and patients with extrauterine lesions involving adnexa and/or pelvic lymph node (PLN) were treated by 5 courses. In addition, 10 courses were given to patients with PAN metastasis. Patients with PLN metastasis received adjuvant chemotherapy, and adjuvant radiation was not part of our institutional protocol. For multivariate regression modeling with proportional hazards, the regression model of Cox was used. Survival curves were analyzed by the Kaplan-Meier method, and analysis of the differences was performed by the log-rank test. The overall incidence of retroperitoneal lymph node metastasis assessed by systematic pelvic and para-aortic lymphadenectomy was 12.0% (34/284) in stages I to IV endometrial carcinoma, and incidences of PLN and PAN metastases were 9.2% (26/284) and 7.4% (21/284), respectively. However, PAN metastasis rate is 50% (13/26) in patients with PLN metastasis. Univariate analysis of prognostic factors revealed that International Federation of Gynecology and Obstetrics clinical stage (P < 0.0001), histological finding (P = 0.0292), myometrial invasion (P < 0.0001), adnexal metastasis (P < 0.0001), lymphovascular space invasion (P < 0.0001), tumor diameter (P = 0.0108), peritoneal cytology (P = 0.0001), and retroperitoneal lymph node metastasis (P < 0.0001) were significantly associated with 10-year overall survival. Survival was not associated with age (P = 0.1558) or cervical involvement (P = 0.1828). A multivariate analysis showed that adnexal metastasis (P = 0.0418) and lymphovascular space invasion (P = 0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year overall survival rates in patients with negative PAN were 96% and 93% versus 72% and 62% in patients with positive PAN (P = 0.006). It is suggested that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy could improve long-term survival in patients with PAN metastasis, although there are only 21 patients with PAN metastasis.

A Prospective Randomized Trial to Study the Impact of Pretreatment FDG-PET for Cervical Cancer Patients With MRI-Detected Positive Pelvic but Negative Para-Aortic Lymphadenopathy

This prospective randomized study was undertaken to determine the possible impact of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) on extrapelvic metastasis detection, radiation field design, and survival outcome for cervical cancer patients with enlarged pelvic nodes on MRI image. Inclusion criteria were patients with newly diagnosed Stage I-IVA cervical cancer and with positive pelvic but negative para-aortic lymph nodes (PALN) as detected by magnetic resonance image and good performance status for concurrent chemoradiotherapy. Eligible patients were randomized to receive either pretreatment FDG-PET (study group) or not (control group). Whole pelvis was the standard irradiation field for the control group and those with no extrapelvic findings on PET. The radiation fields for the rest of the study group were extended to include the PALN region or were modified according to the extrapelvic PET finding. From January 2002 to April 2006, 129 patients were included, and 66 of them were randomized to receive FDG-PET. PET detected seven extrapelvic metastases (11%, 6 PALN and 1 omental node), and four of them remained disease-free after treatment modification. For patients who underwent PET compared with those who did not, there were no differences in the 4-year rates of overall survival (79% vs. 85%, p = 0.65), disease-free survival (75 % vs. 77%, p = 0.64), and distant metastasis-free survival (82% vs. 78%, p = 0.83). Pretreatment FDG-PET in conjunction with magnetic resonance imaging can improve the detection of extrapelvic metastasis, mainly PALN, and help select patients for extended-field radiotherapy. However, the addition of FDG-PET may not translate into survival benefit, even though PALN relapses are reduced.

Prognostic impact of para-aortic lymph node micrometastasis in patients with regional node-positive biliary cancer

The presence of para-aortic lymph node metastasis in biliary cancer has a negative impact on prognosis. The relevance of para-aortic lymph node micrometastasis is unknown. A total of 546 para-aortic lymph nodes from 49 patients with biliary cancer with positive regional nodes and negative para-aortic nodes were immunostained with epithelial marker CAM5.2 (specific for cytokeratins 7 and 8). Immunostained tumour foci were classified as micrometastases or isolated tumour cells (ITCs) according to their size (larger or smaller than 0.2 mm). CAM5.2-positive occult carcinoma cells in para-aortic lymph nodes were detected in nine (18 per cent) of 49 patients and in 18 (3.3 per cent) of 546 para-aortic nodes. There was no difference in postoperative survival between patients with and without CAM5.2-positive para-aortic nodes (P = 0.978), but survival for five patients with micrometastases was significantly worse than that for four patients with only ITCs (P = 0.047). In patients with regional node-positive and para-aortic node-negative biliary cancer, and occult cancer cells in para-aortic lymph nodes, prognosis was significantly worse in those with micrometastases than in patients with only ITCs. An efficient method of intraoperative detection of para-aortic lymph node micrometastases larger than 0.2 mm is needed.

Surgical versus radiographic determination of para‐aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma

Patients with cervical cancer who had negative para-aortic lymph nodes (PALNs) identified by pretreatment surgical staging were compared with patients who had only radiographic exclusion of PALN metastases before they received treatment with pelvic radiation and brachytherapy (RT) plus cisplatin (C)-based chemotherapy. Patients who participated in 1 of 3 Phase III Gynecologic Oncology Group (GOG) trials (GOG 85, GOG 120, and GOG 165) and who were assigned randomly to receive either RT plus C or RT plus C combined with 5-fluorouracil with or without hydroxyurea comprised this retrospective analysis. Patients who had negative PALN status determined by surgical sampling (mandatory in GOG 85 and GOG 120 and optional in GOG 165) were compared with patients who had negative PALN status determined radiographically (GOG 165). Five hundred fifty-five patients underwent surgical PALN sampling (the S group), and 130 patients underwent radiographic evaluation only (the R group). Age, race, histology, and tumor grade were similar. Patients in the R group had better performance status (P < .01), less advanced stage (P = .023), and smaller tumor size (P = .004) compared with patients in the S group, although patients with stage III and IV disease in the S group had better 4-year progression-free survival (48.9% vs 36.3%) and overall survival (54.3% vs 40%) compared with patients in the R group. In multivariate analysis, the R group was associated independently with a poorer prognosis compared with the S group (for disease progression: hazard ratio [HR], 1.35, 95% confidence interval [95% CI], 1.01-1.81; for death: HR, 1.46, 95% CI, 1.08-1.99). Surgical exclusion (compared with radiographic exclusion) of positive PALNs in patients with cervical cancer who received chemoradiation (RT plus C-based chemotherapy) had a significant prognostic impact.

Long-term survival in patients with para-aortic lymph node metastasis with systematic retroperitoneal lymphadenectomy followed by adjuvant chemotherapy in endometrial carcinoma

16011 Background: The purpose of this study was to assess modified radical hysterectomy including systematic pelvic and para- aortic lymphadenectomy followed by adjuvant chemotherapy in patients with para-aortic lymph node metastasis in endometrial carcinoma and to identify the multivariate independent prognostic factors for a long-term survival over the past 10 years. Methods: Between December 1987 and December 2002, we performed modified radical hysterectomy with bilateral salpingo-oophorectomy including systematic pelvic and para-aortic lymphadenectomy, and peritoneal cytology in 284 endometrial carcinoma patients who gave an informed consent at the Department of Gynecologic Oncology of Shikoku Cancer Center. The patients with a tumor confined to the uterus (stage Ic and II) were treated by 3 courses of CEP (cyclophosphamide 750 mg/m2, epirubicin 50 mg/m2, cisplatin 75 mg/m2) regimen 3–4weeks apart, extrauterine lesions involving adnexa and/or pelvic lymph node (PLN), and para-aortic lymph node (PAN) metastasis were treated by 5 and 10 courses, respectively. Multivariate analysis was performed for the prognostic factors and actuarial technique for the survival rate. Results: PLN and PAN metastasis were 9.2% (26/284) and 7.4% (21/284), respectively. The univariate analysis of prognostic factors revealed that FIGO clinical stage, histology, myometrial invasion, adnexal metastasis, lymphvascular space invasion, tumor diameter, peritoneal cytology and retroperitoneal lymph node (RLN) metastasis were significantly associated with 10-year overall survival. A multivariate analysis showed that adnexal metastasis (p=0.0418) and lymphvascular space invasion (p=0.0214) were significantly associated with 10-year overall survival. The 5- and 10-year survival in patients with negative and positive para-aortic lymph node were 96%, 72% and 93%, 62%, respectively (p=0.006). Conclusions: We conclude that surgery with systematic pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy might improve a long-term survival in patients with PAN metastasis in endometrial carcinoma. No significant financial relationships to disclose.

Concomitant weekly carboplatin (CB) and paclitaxel (P) with pelvic radiotherapy (RT) for the treatment of advanced cervical cancer (ACC): A FNCLCC gynecologic group phase I trial

5542 Background: Standard primary treatment for locally ACC is RT with concomitant chemotherapy (CT). CB and P are radiosensitizers with in vitro synergistic action. Methods: Patients (pts) with FIGO stage IIB-IVA negative paraaortic lymph nodes cervical cancer were treated with 6 weekly cycles of CT during pelvic RT (45 Gy) and brachytherapy (BT) according to Table 1 . Each dose escalation step followed a 30-day period of observation on cohorts of 3 to 6 pts depending on dose limiting toxicity (DLT): toxic death; garde (G) 4 neutropenia &gt; 1 week; G 4 toxicity (other hematologic or non-hematologic); any toxicity requiring = 1 week delay in RT, or &gt; 2 dose reductions of CT, or G 3/4 hematologic toxicity &gt; 3 weeks after treatment’s end; unendurable G 3 non hematologic toxicity. Results: 23 pts were included by 5 centers in 5 dose levels (L). Stage distribution: IIB (10), III (11), IVA (2); 20 epidermoid and 3 adenocarcinoma; ECOG: 0 (16), 1 (7). 22 pts received the 6 planned cycles. Median dose of irradiation was 45 Gy (43.2–50) with no toxicity related interruption. 17 pts underwent BT, 2 had hysterectomy and 1 received complementary external irradiation 12 Gy. CT dose reduction was necessary in 4 pts (cycle 5 or 6) and cycles postponed for 10 pts (cycle. 5 or 6). One pt experienced paclitaxel allergy at L1. G 3 anemia and/or neutropenia were reported in 11 pts and G 4 neutropenia = 1 week in 2 pts. Radiodermatitis occurred in 5 pts, asthenia in 3 and nausea in 1. One DLT was observed: unendurable G 3 asthenia + G 3 neutropenia and leucopenia at L3. Clinical and radiological complete response was obtained in 13 pts, 5 PRs and 2 SDs in 20 evaluable pts. Conclusions: Acceptable toxicity and optimal irradiation were possible at L4 in 7 pts. These doses are recommended for future phase II studies of concomitant CT/RT in ACC. [Table: see text] No significant financial relationships to disclose.

Long-Term Follow-Up of a Randomized Trial Comparing Concurrent Single Agent Cisplatin, Cisplatin-Based Combination Chemotherapy, or Hydroxyurea During Pelvic Irradiation for Locally Advanced Cervical Cancer: A Gynecologic Oncology Group Study

We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes. Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events. The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680). Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.

Prise en charge chirurgicale par voie d'abord cœlioscopique du cancer du col utérin occulte découvert après hystérectomie simple

Objectives To assess the feasibility and morbidity of surgical management by combined laparoscopic and vaginal approach after cervical cancer diagnosed at the time of simple hysterectomy. Patients and methods From 2000 to 2005, 10 patients were referred with occult cervical cancer discovered after simple hysterectomy. All these patients had laparoscopy for surgical staging. Results Eight on ten patients had complete laparoscopic staging: pelvic lymphadenectomy ( N = 8), radical colpectomy ( N = 5). Operative time, pelvic lymph nodes resected, postoperative stay were respectively 261.3 minutes (200–400), 27 (23–38), 4.4 days. There were 2 symptomatic lymphocysts. Pelvic lymph nodes were positive for 1 patient with negative paraaortic nodes. Residual disease was present in 2 cases: 1 parametrial and vaginal involvement, 1 ovarian metastasis. 5 patients had adjuvant treatment: 2 combined pelvic external radiotherapy and brachytherapy, 1 pelvic external radiotherapy, 1 pelvic concurrent chemoradiation and 1 brachytherapy only. Two on ten patients needed a laparoconversion, one for ovarian involvement and one for technical failure. With a median follow-up of 29.7 months (4–63), 3 patients recurred. 3 patients recurred above 5 patients with pelvic lymphadenectomy but without parametrectomy versus no recurrence above 5 patients with pelvic lymphadenectomy and parametrectomy. Discussion and conclusion Surgical staging of occult cervical cancer discovered after simple hysterectomy is necessary for indication of adjuvant treatment. Laparoscopy combined with vaginal surgery is feasible and safe, inducing fewer adhesions which is important for adjuvant radiotherapy. The realization of a radical parametrectomy seems to offer a local control of the disease and a decrease in the risk of recurrence, which need to be confirmed by conducting a study with more patients. This emphasize the necessity of creating a national record to register all women managed for occult cervical cancer.

Population characteristics in cervical cancer trials: Search for external validity

The purpose of this study was to compare the characteristics of patients with cervical cancer who were enrolled in cooperative group trials with characteristics of the cervical cancer population of the United States and to determine the generalizability of the results of those trials to the disease population in the United States. Phase III trials in cervical cancer that were conducted by cooperative groups in the United States from 1981 through 1997 were identified. These groups were placed into 4 categories on the basis of disease stage and primary treatment modality: Stage IB, negative pelvic nodes that were treated with radical hysterectomy (n = 277 patients); Stage IB-IIA, positive pelvic nodes that were treated with radical hysterectomy (n = 239 patients); Stage IB 2 , negative pelvic and para-aortic nodes that were treated with radiation therapy (n = 369 patients); and Stage IIB-IVA, negative para-aortic nodes that were treated with radiation therapy (n = 1190 patients). For each category, comparable patients from the Surveillance, Epidemiology, and End Results (SEER) database were identified. The age and ethnic distributions of each study population and the distributions of the SEER program were compared. The age distributions were equivalent, except for patients with IB 2 disease that was treated with radiation therapy where cooperative group subjects were more likely to be younger than 50 years, (odds ratio, 0.17; 95% CI, 0.11-0.26). A statistically significant higher proportion of black and Hispanic women enrolled in cooperative group studies in comparison with surveillance, epidemiology, and end results. Hispanic and black women were recruited proportionately to cooperative group randomized cervical cancer trials in comparison to the United States population. The age distribution of the clinical trial population is also comparable to that of the general population.

A Preliminary Results of a Randomized Trial Comparing Monthly 5-flourouracil and Cisplatin to W eekly Cisplatin A lone Combined with Concurrent Radiotherapy for Locally Advanced Cervical Cancer

To determine the superior chemotherapeutic regimen between monthly 5-FU plus cisplatin (FP) and weekly cisplatin alone in concurrent chemoradiotherapy for locally advanced cervical cancer, the compliance of treatment, response, survival and toxicities were analyzed between the two arms. Between March 1998 and December 2001, 61 patients with locally advanced cervical cancer (stage IIB through IVA) and negative para-aortic lymph nodes were randomly assigned to either 'monthly FP' (arm I, n=34) or 'weekly cisplatin' (arm II, n=27) with concurrent radiotherapy. The patients of arm I received FP (5-FU 1,000 mg/m(2)/day + cisplatin 20 mg/m(2)/day, for 5 days, for 3 cycles at 4 week intervals) and those of arm II received cisplatin (30 mg/m(2)/day, for 6 cycles at 1 week intervals) with concurrent radiotherapy. The radiotherapy consisted of 41.4 approximately 50.4 Gy external beam irradiation in 23 approximately 28 fractions to the whole pelvis, with high dose rate brachytherapy delivering a dose of 30 approximately 35 Gy in 6 approximately 7 fractions to point A. During the brachytherapy, a parametrial boost was delivered. The median follow-up period for survivors was 44 months. The compliance of treatment in monthly FP weekly cisplatin arms were 62 and 81%, respectively. The complete response rates at 3 months were 96 and 88% in arms I and II, respectively. The 4-year overall survival and disease free survival rates were 64 and 54% in the arm I and 77 and 66% in the arm II, respectively. The incidence of hematologic toxicity more than grade 2 was 29% in the arm I and 15% in the arm II. Only one patient in arm I experienced grade 3 gastrointestinal toxicity. No severe genitourinary toxicity was observed. No significant difference was observed in the compliance, responses, survival rates and acute toxicities between the two treatment arms. More patients and further follow up will be required.

Phase I clinical trial of weekly paclitaxel, weekly carboplatin, and concurrent radiotherapy for primary cervical cancer

Objectives Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). Incomplete local control and the appearance of distant disease herald poor survival and warrant evaluation of new primary strategies. Paclitaxel and carboplatin are active agents in recurrent cervical carcinoma, have potent, synergistic in vitro radiosensitization, and are cytotoxic in weekly schedules. This study was done to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly paclitaxel/carboplatin chemoradiotherapy in locally advanced cervix cancer. Methods Women with primary, previously untreated, squamous cell or adenocarcinoma of the cervix, FIGO stage IB 2 to IVA, negative para-aortic lymph nodes, adequate organ function and performance status were eligible. Pelvic RT (45 Gy over 5 weeks—180 cGy/day, four-field) was followed by two brachytherapy applications (Point A low dose rate (LDR): 90 Gy, high dose rate (HDR): 75 Gy). Concurrent weekly CT was paclitaxel 50 mg/m 2 and carboplatin, starting at AUC 1.5 and escalating in three-patient cohorts by AUC 0.5 (Max AUC 3.5). Dose escalation followed a 4-week observation period for toxicity. A grade III–IV toxicity prompted up to three additional patients per dose level. A second event defined DLT. CT was administered concurrently throughout brachytherapy. Results Fifteen patients were enrolled and treated over four dose levels until DLT was reached. Median age was 44 years (range, 23–70); stages: IB2: 1, IIB: 9, IIIA: 1, IIIB: 4. Median RT treatment time was 61 days (range, 55–79). Fourteen patients received brachytherapy (LDR: 8, HDR: 6), and one received external RT only due to cervical stenosis. The median number of weekly CT cycles was seven (range, 6–7). One CT dose was dropped in one patient for a grade II thrombocytopenia. One grade III ANC was observed at dose level II (AUC 2.0) but not seen in three additional patients. At dose level IV (AUC 3.0), two grade III–IV ANC toxicities were observed in two patients (DLT). Nine patients had grade II anemia. One patient had grade III anemia. Grade III/IV nonhematologic toxicity was rare (1/15 GI-nausea/vomiting, 1/15 pneumonia, 1/15 hypokalemia). The MTD of carboplatin is AUC 2.5 with paclitaxel 50 mg/m 2. Median follow-up is 17 months; three patients have recurred and two have died. The estimated 2-year PFS and OS are 80% and 86%. Conclusions Weekly paclitaxel and carboplatin chemoradiation is feasible and active. The MTD for a phase II trial is 50 mg/m 2 and AUC 2.5, respectively.

Optimizing Treatment for Cervical Cancer

There are a number of ways in which surgery, radiation therapy, and more recently chemotherapy have been employed in the treatment of locally advanced cervical cancer. The evidence in favor of chemoradiation in cervical cancer was summarized in a meta-analysis of 19 trials which showed improvement with the concomitant administration of chemotherapy and radiation (CRT), not only in survival (by >10% at 5 years) but also in both local and distant recurrence rates. These results validate the National Cancer Institute Alert (USA) in February 1999, which was based on preliminary evidence from five randomized trials, and stated that concomitant chemoradiotherapy should be considered for the majority of patients with cervical cancer. However, patients with locally advanced disease with negative para-aortic nodes accounted for the majority of those selected for these trials, and the benefits of the addition of chemotherapy to radiation were clearer in stages I and II disease. Acute and late toxicity remain areas of concern. The role of surgery is also undergoing re-evaluation, both in early disease where surgery may offer equal survival to radiation with reduced morbidity, and in more locally advanced cases where recent data have shown surgery preceded by chemotherapy achieves similar gaines in absolute survival compared with radiation alone. The trials involving CRT differed in size, design, accrual period and chemotherapeutic agent used, and there has been extensive debate about optimization of the radiation dose and whether chemotherapy in some of the trials compensates for inadequate radiation dose. However, these factors would not account for the improvement in distant relapse rates observed. Similarly, surgical expertise has been shown to be a major factor affecting outcome in radical procedures, and recent developments in more conservative surgery also improve morbidity in selected cases. The alternative strategy of neoadjuvant chemotherapy prior to surgery (NACT-S) has been evaluated extensively in South America and Italy in groups similar to those in which CRT has been shown to be effective. Although the data are promising, the evidence base for outcome compared with radiation alone is much smaller, and there have been no direct comparisons with CRT. The chemotherapy in CRT may be acting predominantly through a cytotoxic effect as distinct from having a sensitization effect, and hence the rationale for these two approaches (CRT and NACT-S) may be broadly similar, that is, early control of systemic disease as well as additional local control to that achieved by either surgery or radiation alone. The sequential use of further chemotherapy after these strategies is under development. In early disease, surgery and radiation therapy are comparable in terms of efficacy, and the preference for surgery is based on reduced morbidity and the potential to preserve fertility. The addition of platinum-based chemotherapy, either prior to surgery or with radiation improves survival and distant recurrence rates in more locally advanced cases up to stage IIb, or in those patients with adverse risk factors. The available data are insufficient to recommend routine adoption of CRT in earlier (stage Ia2) or more advanced cases (stages III or IV). However, with the enrolment of over 4000 women in randomized trials and mature follow-up, chemoradiation has become an established treatment.

Early-Stage Cervical Adenocarcinoma Treated by Surgical Intent: The Role of Para-aortic Lymph Node Dissection

Objective. Previous reports suggest that cervical adenocarcinomas have a unique pattern of spread and are more apt to metastasize to para-aortic lymph nodes. The purpose of this study was to further define the node of para-aortic lymph node dissection in early-stage cervical adenocarcinoma treated by surgical intent.Methods. Institutional review board approval was obtained to perform a computerized search of the data of all women diagnosed with cervical adenocarcinoma between 1982 and 2000. Hospital charts were retrospectively reviewed. Follow-up was obtained from the tumor registry, medical records, and correspondence with health care providers.Results. Three hundred (87%) of 345 early-stage (FIGO IA1–IIA) cervical adenocarcinoma patients were primarily treated by surgical intent. Two hundred seventy-six underwent pelvic and para-aortic node dissection (n = 69) or pelvic node dissection only (n = 207); 24 had no lymph node dissection. The median number of lymph nodes removed was 13 pelvic (range, 1–58) and 3 para-aortic (range, 1–17). Three (4%) of 69 patients had para-aortic nodal metastases. Each had either grossly evident para-aortic adenopathy (n = 2) or an adnexal metastasis. Thirty-six of 40 women developing recurrent disease had at least some component of pelvic recurrence; 4 had only extrapelvic disease. Three patients undergoing para-aortic node dissection developed an isolated extrapelvic recurrence despite originally negative para-aortic nodes (n = 2) or treatment by extended-field radiation for para-aortic metastases. One woman undergoing only pelvic node dissection had an isolated extrapelvic recurrence despite originally negative nodes.Conclusions. Early-stage cervical adenocarcinoma primarily treated by surgical intent has a very low risk of para-aortic metastases. These were detected only when there was gross evidence of nodal or adnexal disease.