Primary Surgical Staging Research Articles

Risk factors for lymph node metastasis in apparent early-stage epithelial ovarian cancer: Implications for surgical staging

Objectives The extent of lymphadenectomy to be performed in apparent early-stage epithelial ovarian cancer (EOC) is not well defined. We evaluated the patterns of lymphatic spread in apparent early-stage EOC and risk factors for lymph node metastasis, as these have potential implications for clinical decision making. Methods All cases of apparent early-stage EOC diagnosed at our institution between January 1994 and December 2003 were retrospectively identified. Apparent early-stage EOC was defined as gross disease that appeared confined to the pelvis without abdominal spread at the time of initial exploration. Demographics, pathologic findings, staging procedures performed, and clinical impression at surgery were analyzed. Patterns of lymph node positivity and risk factors associated with upstaging were assessed. Results One hundred and ninety patients with apparent early-stage EOC undergoing primary surgical staging met criteria for inclusion. All patients had at least some pathologic assessment of lymph nodes, with 115 having both bilateral pelvic and paraaortic lymphadenectomy performed. After review of pathology and operative reports, the final FIGO staging within the cohort was 54 IA (28.4%), 10 IB (5.3%), 51 IC (26.8%), 1 IIA (0.5%), 4 IIB (2.1%), 37 IIC (19.5%), 8 IIIA (4.2%), 25 IIIC (13.2%). Overall 25/190 (13%) had lymph nodes metastasis as follows: 8 (32%) had positive pelvic nodes, 12 (48%) had positive paraaortic nodes, and 5 (20%) had both positive pelvic and paraaortic lymph nodes. Significant risk factors for lymph node metastasis included bilateral vs. unilateral primary lesion (26.8% vs. 7.5%, p < 0.001), positive cytologic washings vs. negative (22.4% vs. 9.1%, p = 0.012), ascites vs. no ascites (28.2% vs. 9.3%, p = 0.002), serous vs. other histology (28% vs. 9%, p = 0.001), grade 1 vs. grade 2 vs. grade 3 disease (2.7% vs. 1.9% vs. 23.2%, p < 0.001), and preoperative CA 125 levels of > 35 vs. ≤ 35 U/ml (22.4% vs.0% p = 0.006). No patients with mucinous cancers ( n = 29) had lymph node metastases. Patterns of LN metastases were largely independent of laterality of primary lesions: among those with unilateral lesions and positive nodes ( n = 10), 5 (50%) had ipsilateral lymph node involvement, 4 (40%) had bilateral involvement, and 1 (10%) had isolated contralateral lymph nodes positive. Conclusions Complete surgical staging in EOC patients with gross disease confined to the ovaries and pelvis should include bilateral pelvic and paraaortic lymphadenectomy. Even in patients with unilateral lesions, lymph node metastases are commonly bilateral. Bilateral ovarian lesions, positive cytology, presence of ascites, high grade histology, and serous histology are risk factors for lymph node involvement. This information may be helpful in counseling patients presenting for consideration of re-staging after unexpected findings of malignancy.

Patterns of spread and recurrence of sex cord-stromal tumors of the ovary

Objective. Sex cord-stromal tumors are an uncommon type of ovarian neoplasm and limited data are available in the literature to guide clinical management. Recent published series suggested a lack of lymph node involvement and recommended abandonment of the lymph node dissection as part of the primary surgical staging of these tumors. To confirm these findings, we evaluated pathologic findings in women undergoing surgical management of sex cord-stromal tumors in the Seattle metropolitan area. Methods. A retrospective multi-institutional review of all patients treated with sex cord-stromal tumors at University of Washington Medical Center and Swedish Medical Center in Seattle was conducted. Information was collected on the pathology, evaluation, and treatment of these patients. Results. A total of 87 patients were available for analysis, the majority of whom had adult granulosa cell tumors (82%) and Sertoli–Leydig cell tumors (13%). Of these patients, 68% had complete or partial surgical staging procedures, and 47 patients had some nodal tissue examined as part of the initial or restaging procedure. All nodes examined were negative. Tumor size was significantly associated with risk of recurrent disease, with a 20% increase in the hazard of recurrence for each increase of tumor size of 1 cm (HR, 1.20; 95% CI, 1.11–1.07). Conclusions. This study confirms the finding that lymph node metastasis are rare in sex-cord stromal tumors. These findings support the hypothesis that routine lymphadenectomy provides limited additional information in the management of these patients and can be omitted from the primary surgical staging procedure or secondary restaging procedures.

Post-treatment [18F]FDG maximum standardized uptake value as a prognostic marker of recurrence in endometrial carcinoma

The purpose of this study was to determine whether post-treatment [(18)F]fluorodeoxyglucose (FDG) uptake measured as the maximum standardized uptake value (SUV(max)) by integrated positron emission tomography (PET)/computed tomography (CT) imaging has prognostic significance in patients with endometrial carcinoma. Patients previously treated by primary surgical staging for endometrial carcinoma were imaged with integrated FDG PET/CT during surveillance. PET/CT findings were compared with histological or clinical evaluation, and the relationship between SUV(max) on PET/CT and recurrence was examined. A total of 61 patients were eligible for analysis. Medical records were retrospectively reviewed for clinical data, treatment modalities and outcome. The median duration of follow-up was 31 months (range 6-102 months) post-treatment. SUV(max) levels were inversely associated with disease-free survival (DFS). Patients were divided into two groups according to SUV(max) (< 4.25 versus ≥ 4.25). The Kaplan-Meier survival graph showed a significant difference in DFS between groups [p < 0.001, hazard ratio (HR) 12.959, 95% confidence interval (CI) 3.650-46.011]. In multivariate analyses, post-treatment SUV(max) (uncategorized values) evaluated by surveillance PET/CT (p = 0.001, HR 1.199, 95% CI 1.077-1.334) and serous adenocarcinoma histology (p = 0.028, HR 5.594, 95% CI 1.207-25.931) were significantly associated with recurrence. Post-treatment FDG uptake as measured by SUV(max) showed a significant association with recurrence in patients with endometrial carcinoma and may be used as a new useful prognostic marker.

CON: Not All Patients with Endometrial Cancer with Extrauterine Disease Should Receive Chemotherapy After Any Indicated Surgery

Introduction The adoption of primary surgical therapy and staging (including lymph node assessment and/or dissection) has given us a better understanding of prognostic groups, risk factors, and patterns of recurrence.1 Furthermore, the recognition of clear-cell and papillary carcinomas of the endometrium (PCE) as distinct subtypes of endometrial carcinoma has provided further information along these lines.2,3 Although clinicians now have, in many cases, a more complete understanding of disease extent and surgicopathologic features in an individual patient, the manner in which this information should affect the choice of adjuvant therapy is still debated. Radiation therapy (RT) has long been used as adjunctive or primary therapy in patients with endometrial carcinoma. Prospective and retrospective series uniformly demonstrate a significant improvement in pelvic control.4,5 A survival benefit has, however, been more difficult to demonstrate. The recognition that patients with locally advanced disease also have a significant rate of failure outside the pelvis has given impetus to the use of chemotherapy in this group of patients. Publication of the results of Gynecologic Oncology Group (GOG) study 122 established a role for adjuvant chemotherapy in the management of patients with selected stage III and IV endometrial cancers.6 Since that time, other studies, using varying eligibility criteria and trial designs, have been performed, many of which support the notion that adjuvant chemotherapy improves outcomes for the patient population generally defined as having locally advanced endometrial carcinoma; however, not all studies have shown a benefit for chemotherapy over radiation therapy alone.7,8 Furthermore, questions arise regarding patient selection in terms of how “locally advanced” should be defined. Do the data conclusively indicate that every patient with any extrauterine disease should receive chemotherapy? Or are certain subsets most likely to benefit? Finally, because the patient population under consideration typically includes older women with various comorbid illnesses, it is not clear that the toxicities of systemic therapy are, in all cases, outweighed by the therapeutic benefit that has been demonstrated. The purpose of this article is to discuss the various subpopulations of patients with extrauterine involvement from endometrial cancer, review the relevant literature that potentially inform decisions regarding adjuvant therapy in these subpopulations, mention ongoing clinical trials, and offer some general recommendations regarding the selection of adjuvant therapies in patients with extrauterine endometrial cancer, including the possibility that, in selected cases, systemic therapy can be reasonably withheld.

The association of ERCC1 and clinical outcomes of women with advanced ovarian cancer

5575 Background: To determine the significance of excision repair cross complementation group 1 (ERCC1) in optimally debulked stage IIIC serous ovarian cancer after platinum and taxol chemotherapy. Methods: All patients were identified from two academic health centers. Pretreatment tumor biopsy specimens were analyzed for ERCC1 expression by immunohistochemistry. Patients were divided into two groups: those who recurred or had persistent disease within 12 months, and those who recurred after 12 months. Pathologic evaluation was performed without identifying clinical information. Time to progression and survival analyses were estimated using Kaplan Meier method. Results: Of 96 patients, the median age was 59 years. 68% were White, 18% Asian and 13% Other. All patients underwent primary surgical staging and were diagnosed with FIGO stage IIIC disease. All tumors were of papillary serous histology. The grading of immunostaining revealed that 16% of tumors had grade 1, 60% grade 2, and 24% had grade 3 stainin...

The incidence of pelvic lymph node metastasis by FIGO staging for patients with adequately surgically staged endometrial adenocarcinoma of endometrioid histology

The seminal Gynecologic Oncology Group study on surgical pathologic spread patterns of endometrial cancer demonstrated the risk of pelvic lymph node metastasis for clinical stage I endometrial cancer based on tumor grade and thirds of myometrial invasion. However, the FIGO staging system assigns surgical stage by categorizing depth of myometrial invasion in halves. The objective of this study was to determine the incidence of pelvic lymph node metastasis in endometrial cancer based on tumor grade and myometrial invasion as per the current FIGO staging system. We reviewed the records of all patients who underwent primary surgical staging for clinical stage I endometrial cancer at our institution between May 1993 and November 2005. To make the study cohort as homogeneous as possible, we included only cases of endometrioid histology. We also included only patients who had adequate staging, which was defined as a total hysterectomy with removal of at least eight pelvic lymph nodes. During the study period, 1036 patients underwent primary surgery for endometrial cancer. The study cohort was composed of the 349 patients who met study inclusion criteria. Distribution of tumor grade was as follows: grade 1, 80 (23%); grade 2, 182 (52%); and grade 3, 87 (25%). Overall, 30 patients (9%) had pelvic lymph node metastasis. The incidence of pelvic lymph node metastasis in relation to tumor grade and depth of myometrial invasion (none, inner half, and outer half) was as follows: grade 1-0%, 0%, and 0%, respectively; grade 2-4%, 10%, and 17%, respectively; and grade 3-0%, 7%, and 28%, respectively. We determined the incidence of pelvic nodal metastasis in a large cohort of endometrial cancer patients of uniform histologic subtype in relation to tumor grade and a one-half myometrial invasion cutoff. These data are more applicable to current surgical practice than the previously described one-third myometrial invasion cutoff results.

Primary Surgery and Chemotherapy Improve Ovarian Cancer Survival

Recommendations for optimal treatment of epithelial ovarian cancer include primary surgical staging accompanied by adjuvant chemotherapy as indicated.

INV 10 Primary surgical treatment and staging for cutaneous melanoma

INV 10 Primary surgical treatment and staging for cutaneous melanoma

Clinical Experience of 6 Cases of Primary Tubal Cancer

Objective : Primary tubal cancer is a rare tumor that histologically and clinically resembles primary ovary cancer. The purpose of this study was to evaluate the clinical experience of 6 patients with primary tubal cancer. Methods : The following parameters were assessed: age, menstruation history, parity, PAP smear status, presenting symptoms, serum CA-125 levels, characteristic sonographic findings, accuracy of preoperative diagnosis, mode of surgery, lymph node metastasis, presence of ascites, tumor grade, stage, and administered postoperative chemotherapy. The 6 patients with primary tubal cancer were diagnosed and treated at the Department of Obstetrics and Gynecology, Ajou Medical Center from March 1998 to March 2004. Results : The mean age was 53.3 years. The presenting symptoms consisted of vaginal spotting, abdominal pain, abdominal discomfort, and dyspnea. Only one patient was preoperatively diagnosed as primary tubal cancer, while the remaining 4 patients were diagnosed as primary ovary cancer. The postoperative pathology revealed 5 cases of serous papillary adenocarcinoma and 1 case of primary transitional cell carcinoma. Three patients were stage III, while the rest were stages I, II, and IV, respectively. Multi-drug chemotherapy was administered to all six patients postoperatively. Follow-up comprised serial serum CA-125 level measurements and computerized tomography scans. Conclusion : Primary tubal cancer is rarely diagnosed preoperatively. The treatment approach is similar to that of ovarian cancer, and includes primary surgical staging operation comprising total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative adjuvant chemotherapy. The prognosis is similar to that of primary ovarian cancer.

Can we rely on the size of the lymph node in determining nodal metastasis in ovarian carcinoma?

This study endeavored to determine whether lymph node size is a reliable indicator in determining lymph node metastasis in common epithelial ovarian cancer. We reviewed pathologic sections of pelvic and para-aortic lymph nodes removed from 104 ovarian carcinoma patients who underwent either primary surgical staging or secondary surgery from January 1994 to July 2001. All sections of each individual node were measured in two dimensions. The different sizes of nodes were studied statistically to determine the optimal sensitivity and specificity in predicting cancer metastasis. A nodal size of 10 mm was a specific point of interest. Of 2069 total nodes obtained, 110 nodes (5.3%) had metastatic cancer. More than half (55.4%) of these positive nodes had a nodal long axis of 10 mm and less. The sensitivity and specificity of nodal size at 10 mm were 44.5% and 81.1%, respectively. We conclude that lymph node size is not a good indicator in determining epithelial ovarian cancer metastasis. Mere sampling of only the enlarged nodes does not reflect the true positive incidence of nodal metastasis. To avoid inaccurate staging and improper management, complete lymph node dissection is proposed as part of surgical staging for ovarian cancer.

Can we rely on the size of the lymph node in determining nodal metastasis in ovarian carcinoma?

This study endeavored to determine whether lymph node size is a reliable indicator in determining lymph node metastasis in common epithelial ovarian cancer. We reviewed pathologic sections of pelvic and para-aortic lymph nodes removed from 104 ovarian carcinoma patients who underwent either primary surgical staging or secondary surgery from January 1994 to July 2001. All sections of each individual node were measured in two dimensions. The different sizes of nodes were studied statistically to determine the optimal sensitivity and specificity in predicting cancer metastasis. A nodal size of 10 mm was a specific point of interest. Of 2069 total nodes obtained, 110 nodes (5.3%) had metastatic cancer. More than half (55.4%) of these positive nodes had a nodal long axis of 10 mm and less. The sensitivity and specificity of nodal size at 10 mm were 44.5% and 81.1%, respectively. We conclude that lymph node size is not a good indicator in determining epithelial ovarian cancer metastasis. Mere sampling of only the enlarged nodes does not reflect the true positive incidence of nodal metastasis. To avoid inaccurate staging and improper management, complete lymph node dissection is proposed as part of surgical staging for ovarian cancer.

Multizentrische Umfrage zum Stellenwert der Lymphonodektomie beim Endometriumkarzinom in Deutschland

Einleitung und Fragestellung: Im Management des Endometriumkarzinoms hat sich das primär chirurgische Staging etablieren können. Hierbei wird von verschiedenen Arbeitsgruppen auch die Lymphonodektomie empfohlen. Im Gegensatz zur prognostischen Bedeutung des Lymphknotenstatus ist der therapeutische Nutzen der Lymphonodektomie unklar. Methodik: Im Rahmen einer Querschnittsstudie im Zeitraum von Oktober 2001 bis Januar 2002 wurden insgesamt 1030 standardisierte Fragebögen an Frauenkliniken in Deutschland versendet. Ergebnisse: 595 Antworten (58%) konnten ausgewertet werden. Die Zusammensetzung war wie folgt: Universitätskliniken 5,2%, Kliniken der Maximalversorgung 69,7% und Regelversorgung 25%. Führen Sie eine Lymphonodektomie beim Endometriumkarzinom durch? Nur 7,3% (95% Kl: 5,3–9,7%) gaben an, nie eine Lymphonodektomie durchzuführen, 62,9% (95 Kl: 58,9–66,9%) führen diese in ausgewählten Fällen, 29,7% (95% Kl: 26–33.7%) regelmässig durch. Welche Methode der Lymphonodektomie wenden Sie an? 27,1% (95 Kl: 23,2–31,4%) setzen das «Sampling», 72,9% (95 Kl: 68,6–76,8%) die systematische Entfernung ein. 26,6% (95% Kl: 22,8–30,6%) lymphonodektomieren sowohl pelvin als auch paraaortal. Welche Intention verfolgen Sie mit der Lymphonodektomie? 31,7% (95% Kl: 22,8–30,6%) führen diese aus Gründen des Stagings, 3,1% (95% Kl: 1,8–4,9%) wegen des Überlebens und 65,2% (95% Kl: 60,9–69,3%) wegen beidem durch. 94,5% (95% Kl: 92,1–96,3%) gaben an, dass der Lymphknotenbefall einen Einfluss auf die Wahl der adjuvanten Behandlung besitzt. 76,8% (95% Kl: 72,8–80,4%) bzw. 36,9% (95 Kl: 46,9–56.5%) wählen in den Stadien I/II bzw. III/IV eine Radiotherapie, 20,4% (95% Kl: 16,9–24,2%) bzw. 51,7% (95% Kl: 46,9–56.5%) eine Radiochemotherapie. Schlussfolgerungen: Die vorliegenden Ergebnisse sollten als Grundlage für die Konzeption prospektiver, multizentrischer Studien zum operativen und zytostatischen Management dienen.

Predictors of Recurrence in Surgical Stage II Endometrial Adenocarcinoma

Objective. A retrospective review of surgical stage II endometrial carcinoma was performed to evaluate clinical course, treatment, recurrence rate, and survival.Methods. A list of patients with clinical and surgical stage II endometrial carcinoma was obtained through the tumor registry and from the pathology department from 1988 to 1996. Data were collected on all cases of patients with endometrial carcinoma meeting stage II criteria by FIGO surgical staging. Variables including stage, histology, grade, lymph vascular space invasion (LVI), type and extent of surgery, radiation type and amount, smoking, menstrual status, parity, and age were evaluated for their predictive ability of disease recurrence. Cox proportional hazard regression models were used to examine the potential predictors of time to relapse univariately and multivariately.Results. Of patients identified, 65 underwent primary surgical staging. Only adenocarcinomas were included. Mean follow-up time was 4.7 years (range 0.2–9.6 years). Postoperative radiation was given to 85.7% of patients. There were 10 patients (15.4%) with recurrence of disease with a mean time to recurrence of 25 months. Five-year disease-specific survival was 93%. The only significant predictor of time to relapse was LVI (P = 0.002) in the multivariate analysis.Conclusion. This retrospective review suggests that primary surgery followed by postoperative radiation therapy gives excellent results in surgical stage II disease. LVI appears to be a strong predictor of disease recurrence regardless of postoperative radiation therapy. It is difficult to draw conclusions about the type and amount of radiation given because recurrence rate is so low; however, it is reasonable to continue adjuvant radiation especially in cases where LVI is identified.

Isolated appendiceal metastasis in early ovarian carcinoma

The appendix was identified as the only site of extrapelvic metastatic ovarian carcinoma at the time of primary surgical staging. Isolated appendiceal metastasis has not been previously reported in comprehensively staged early stage ovarian carcinoma. Routine appendectomy during surgical staging of ovarian carcinoma should be considered.

Transitional cell carcinoma of the ovary

Five patients with transitional cell carcinoma of the ovary constituted 1.0% of all patients with primary ovarian carcinoma (5/494) managed in the study period (1984-93). The average age at diagnosis was 59.2 years. All the patients presented with a pelvic mass. The average size of the primary tumoral mass at surgery was 5.2 cm. Only one patient had grossly bilateral involvement. All of the patients were subjected to a primary surgical staging procedure. One patient had stage IIA, two had stage IIB, one had stage IIIC and one had stage IVB disease. Four patients were treated with adjuvant multiagent chemotherapy consisting of cisplatinum and cyclophosphamide for 6 cycles. The other patient received monthly melphalan for 10 courses. Three of the patients were subjected to a second-look procedure. Of them, one with stage IIA disease was found to be negative for tumor after melphelan chemotherapy. This patient is still alive. While the patient with stage IIB disease was found to be tumor-free, the patient with stage IIIC disease had macroscopic tumor at second-look. The other patients with stage IIB and IVB disease were lost to follow-up after 6 months. Four of the patients had grade 3 disease. While epithelim membrane antigen was positive in tumors, intermediate filaments such as vimentin and desmin could not be demonstrated in any. Absence of stromal calcification and CEA immunohistochemical staining, which are common in Brenner tumors, as well as the presence in almost all cases of high grade disease in advanced stages appear to support the establishment of transitional cell carcinoma of the ovary as a separate entity.

Surgical management of ovarian cancer.

Although several surgical approaches to the diagnosis and management of epithelial ovarian cancer are now standard, surprisingly few prospective data exist to support many of these procedures. However, retrospective data have accumulated over the past decade, much of it very recent, which allow clinicians to make informed decisions regarding most of the commonly performed procedures. This review is an attempt to critically evaluate the best available data regarding the following procedures: primary surgical staging, primary cytoreductive surgery, second look laparotomy and secondary cytoreductive surgery, and palliative surgery for relief of bowel obstruction. We conclude that there is evidence to support the continued use of primary surgical staging and primary cytoreductive surgery. However, data in support of second look laparotomy and secondary cytoreductive surgery are lacking, and we recommend that these procedures not be performed on a routine basis. Finally, we conclude that palliative surgery is hazardous at best and results in questionable benefits for most patients.

Management of Early-Stage Oyarian Cancer

Approximately 30% of patients with epithelial ovarian cancer present with localized or early-stage disease. Accuracy of staging is dependent on careful surgical staging. Subsets of patients with specific prognostic factors have now been identified who do not require additional therapy after proper primary surgical staging. Poor prognosis patients do require adjuvant therapy. Whole abdominal irradiation, intraperitoneal P32, and single agent and combination chemotherapy have been utilized. The optimal therapy or whether any therapy is truly effective remains unknown.

Lymph node metastasis in early endometrium cancer.

The incidences of pelvic and paraaortic lymph node metastases in 106 patients with clinical Stage 1 endometrium cancer are presented. All patients were primarily surgically staged and treatment consisted of peritoneal cytology assessment, type II radical hysterectomy, bilateral salpingooophorectomy, pelvic and paraaortic total lymphadenectomy. Pelvic lymph node metastases were present in 15.1% and paraaortic lymph node metastases in 8.5% of the patients. Multiple prognostic factors were evaluated in respect to nodal status. This study adds credence to primary surgical staging with total pelvic and paraaortic lymphadenectomy regardless of presence or absence of the various risk factors.

The role of postoperative alkylating agent therapy in early-stage epithelial ovarian cancer.

Forty-six patients with early (Stage I and II) ovarian cancer referred as free of residual disease after primary surgery, selected for high-risk features, were treated with adjuvant single-agent alkylating therapy comprising either intravenous cyclophosphamide (1 g/m2) in 36 patients, or oral melphalan (0.2 mg/kg daily for 5 days) in eight. Cyclophosphamide was repeated every 3 weeks for 10 cycles and melphalan every 6 weeks for 12 cycles. With a median follow-up of 36+ months, 18 patients have relapsed. The actuarial 5-year relapse-free survival was 48% and the overall 5-year survival was 54%; median survival was 84 months. Pretreatment FIGO stage was the single most important predictor of relapse-free and overall survival duration. For patients with Stage IA and IB tumours the 5-year actuarial relapse-free survival was 89%; for patients with stage IC and II (all substages), the 5-year relapse-free survival was 24% (P = 0.001). For this latter group adjuvant single alkylating agent therapy was not adequate and alternative therapeutic regimens are required. The problem of suboptimal primary surgical staging is also addressed.