Primary Staging Surgery Research Articles

Analysis of para-aortic lymphadenectomy up to the level of the renal vessels in apparent early-stage ovarian cancer

ObjectiveThe aim of this study was to evaluate the impact of para-aortic lymphadenectomy up to the renal vessels on the accurate staging in ovarian cancer patients presumed preoperatively to be confined to the ovary.MethodsWe retrospectively analyzed data on 124 patients with primary epithelial ovarian cancer who were preoperatively thought to have tumor confined to the ovary and underwent primary staging surgery. The distribution of lymph node metastasis and various risk factors for nodal involvement were investigated.ResultsSurgical staging yielded: 87 (70.2%) patients had International Federation of Gynecology and Obstetrics (FIGO) stage I disease and 37 (29.8%) patients had stage II-III disease: 4 IIA, 6 IIB, 9 IIC, 1 IIIA, and 17 IIIC. Eighty-six patients had pelvic lymphadenectomy only and 69 had pelvic and para-aortic lymphadenectomy. Lymph node metastases were found in 17 (24.6%) of 69 patients; 5 (7.2%) patients had lymph node metastasis in the pelvic lymph nodes only, 8 (11.6%) in the para-aortic lymph nodes only, and 4 (5.8%) in both pelvic and para-aortic lymph nodes. Six (8.7%) patients had lymph node metastasis in the para-aortic lymph node above the level of the inferior mesenteric artery. On multivariate analysis, grade 3 tumor (p=0.01) and positive cytology (p=0.03) were independent predictors for lymph node metastasis.ConclusionA substantial number of patients with apparently early ovarian cancer had upstaged disease. Of patients who underwent lymphadenectomy, some patients had lymph node metastasis above the level of the inferior mesenteric artery. Para-aortic lymphadenectomy up to the renal vessels may detect occult metastasis and be of help in tailoring appropriate adjuvant treatment as well as giving useful information about the prognosis.

Roles of E-cadherin and Cyclooxygenase Enzymes in Predicting Different Survival Patterns of Optimally Cytoreduced Serous Ovarian Cancer Patients

The relation between cyclooxygenase enzymes and E-cadherin, along with the roles of these markers in the prediction of survival in optimally cytoreduced serous ovarian cancer patients was investigated. Individuals who underwent primary staging surgery and achieved optimal cytoreduction (largest residual tumor volume<1 cm) constituted the study population. Specimens of 32 cases were immunohistochemically examined for cyclooxygenase-1, cyclooxygenase-2, and E-cadherin. Two could not be evaluated for E-cadherin and cyclooxygenase-1. Overall, 14/30, 19/30, and 15/32 cases were positive for E-cadherin, cyclooxygenase-1, and cyclooxygenase-2, respectively. The expressions of E-cadherin and cyclooxygenase-2 were inversely correlated (p:0.02). E-cadherin expression was related with favorable survival (p<0.001). The relation between the expression of cyclooxygenase enzymes and poor survival did not reach statistical significance. On multivariate analysis, E-cadherin appeared as an independent prognostic factor for survival. In conclusion, E-cadherin expression is strongly linked with favorable survival. E-cadherin and cyclooxygenase 2 may interact with each other during the carcinogenesis-invasion process. Further studies clarifying the relation between E-cadherin and cyclooxygenase enzymes may lead to new preventive and therapeutic targets in ovarian cancer.

Should be para-aortic lymphadenectomy up to the level of the renal vein mandatory in ovarian cancer patients presenting ovarian cancer presumed to be confined to the ovary?

Original Article pISSN 2005-0380 eISSN 2005-0399 J Gynecol Oncol Vol. 24, No. 1:29-36 http://dx.doi.org/10.3802/jgo.2013.24.1.29 Analysis of para-aortic lymphadenectomy up to the level of the renal vessels in apparent early-stage ovarian cancer Suk-Joon Chang 1 , Robert E. Bristow 2 , Hee-Sug Ryu 1 Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea; 2 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine School of Medicine, Orange, CA, USA Objective: The aim of this study was to evaluate the impact of para-aortic lymphadenectomy up to the renal vessels on the accurate staging in ovarian cancer patients presumed preoperatively to be confined to the ovary. Methods: We retrospectively analyzed data on 124 patients with primary epithelial ovarian cancer who were preoperatively thought to have tumor confined to the ovary and underwent primary staging surgery. The distribution of lymph node meta­ stasis and various risk factors for nodal involvement were investigated. Results: Surgical staging yielded: 87 (70.2%) patients had International Federation of Gynecology and Obstetrics (FIGO) stage I disease and 37 (29.8%) patients had stage II-III disease: 4 IIA, 6 IIB, 9 IIC, 1 IIIA, and 17 IIIC. Eighty-six patients had pelvic lymphadenectomy only and 69 had pelvic and para-aortic lymphadenectomy. Lymph node metastases were found in 17 (24.6%) of 69 patients; 5 (7.2%) patients had lymph node metastasis in the pelvic lymph nodes only, 8 (11.6%) in the para-aortic lymph nodes only, and 4 (5.8%) in both pelvic and para-aortic lymph nodes. Six (8.7%) patients had lymph node metastasis in the para- aortic lymph node above the level of the inferior mesenteric artery. On multivariate analysis, grade 3 tumor (p=0.01) and positive cytology (p=0.03) were independent predictors for lymph node metastasis. Conclusion: A substantial number of patients with apparently early ovarian cancer had upstaged disease. Of patients who underwent lymphadenectomy, some patients had lymph node metastasis above the level of the inferior mesenteric artery. Para- aortic lymphadenectomy up to the renal vessels may detect occult metastasis and be of help in tailoring appropriate adjuvant treatment as well as giving useful information about the prognosis. Keywords: Early-stage ovarian cancer, Lymph node metastasis, Para-aortic lymphadenectomy INTRODUCTION Ovarian cancer remains one of the major causes of death from the female genital tract malignancy worldwide, and in Received May 23, 2012, Revised Jun 3, 2012, Accepted Jun 5, 2012 Correspondence to Suk-Joon Chang Department of Obstetrics and Gynecology, Ajou University School of Medicine, 206 World cup-ro, Yeongtong-gu, Suwon 443-721, Korea. Tel: +82-31-219-5251, Fax: +82-31-219-5245, E-mail: drchang@ajou.ac.kr Correspondence to Robert E. Bristow Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine School of Medicine, 101 The City Drive, Building 56, Room 260, Orange, CA 92868, USA. Tel: +1-714-456-8000, Fax: +1-714-456- 7754, E-mail: rbristow@uci.edu the United States, 21,990 new cases and 15,460 deaths were estimated in 2011 [1]. Approximately 25% of ovarian cancer patients are diagnosed with early-stage disease at the time of initial treatment [2]. Surgical staging is a critical aspect of early ovarian cancer as well as advanced ovarian cancer because the International Federation of Gynecology and Obstetrics (FIGO) staging based on surgical and pathologic findings is one of the most important prognostic factors [3]. Accurate surgical staging for early-stage ovarian cancer patients has great significance, permitting accurate estimation of the true extent of disease with detection of occult disease, and providing patients with appropriate information about the prognosis and adjuvant treatment. Up to 30% of patients with apparent early-stage ovarian cancer are found to have extra- Copyright © 2013. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.ejgo.org

Neoadjuvant chemotherapy or primary surgery for stage III/IV ovarian cancer: contribution of diagnostic laparoscopy

BackgroundThe aims of this retrospective study were to evaluate laparoscopic triage of patients with advanced ovarian cancer towards primary surgery or neoadjuvant chemotherapy, and to analyze outcome according to the treatment.MethodsBetween January 2001 and December 2006, 55 patients with stage III – IV ovarian cancer underwent diagnostic laparoscopy. Primary surgery was performed when complete cytoreduction was considered feasible, while the other patients received neoadjuvant chemotherapy (platinum-based combination with taxanes) and interval surgery. All the patients received adjuvant chemotherapy.ResultsPatients treated with neoadjuvant chemotherapy (n = 29) had a higher mean body mass index (P = 0.048), higher serum CA 125 levels (P = 0.026), and more metastases (P = 0.045) than patients treated with primary surgery (n = 26). In patients treated with primary surgery, complete cytoreduction and a residual tumour size ≤ 2 cm were obtained in respectively 54% and 77% of cases. Complete cytoreduction was achieved in respectively 100% and 33% of cases when primary surgery was performed by an oncologic gynaecologist and by a non-oncologic gynaecologist (P = 0.002). Interval surgery yielded complete cytoreduction and a residual tumour size ≤ 2 cm in respectively 73% and 85% of cases. With a median follow-up of 24 months (range 7 – 78 months), the survival rates after primary surgery and interval surgery were 61% and 66% respectively.ConclusionDiagnostic laparoscopy is useful for identifying patients with stage III/IV ovarian cancer who qualify for primary cytoreduction. Surgeon experience was a determining factor for the success of complete cytoreduction.

Population-based cohort follow-up study of all patients operated for borderline ovarian tumor in western Sweden during an 11-year period

Borderline ovarian tumors (BOTs) make up around 10-20% of all epithelial ovarian tumors. The aim of the present study was to investigate the outcome of a complete large population-based cohort of patients treated for BOT. All patients (n= 399) treated for BOT in the western part of Sweden (population around 1.6 million) between 1993 and 2004 were followed. The treatment consisted of primary staging surgery with addition of platinum-based adjuvant chemotherapy for the majority of aneuploid tumors. Data relating to the surgical procedure, FIGO stage, histopathology, ploidy status, adjuvant chemotherapy, and disease state (recurrence or death) at follow-up visits were continuously entered into a cancer quality registry. Data concerning cases and deaths were also controlled against the Swedish National Cancer Registry. The median age of the BOT patients was 55 years (range 16-90). The relative 5- and 10-year survivals were 99.9% (95% CI 96.3-102.4) and 103.5% (95% CI 97.2-108.2), respectively. Aneuploidy was found in 63 (17%) patients, with significantly more aneuploid tumors found among patients of older (>60 years) age. Out of the 399 patients, 8 had recurrence of the disease. Three of the eight patients died from the disease. Five patients with recurrence are alive, three of these patients with no signs of disease after additional treatment. This complete long-term follow-up of a large population-based cohort of BOT patients shows that there is a good overall survival in this patient group.

5032 POSTER Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix cancer

To determine progression-free survival (PFS) and overall survival (OS) in women with completely resected stage I or II carcinosarcoma of the uterus treated with adjuvant ifosfamide and cisplatin, and to assess the toxicity of this regimen.Eligible patients had histologically confirmed carcinosarcoma (mixed mesodermal tumor) and no postoperative radiotherapy following complete resection for clinical stage I or II disease. They were to have adequate renal, hepatic, and hematologic functions and performance status of 2 or less. Study entry was to be within 8 weeks of hysterectomy. Patients with previous chemotherapy, or other noncutaneous malignancies, were ineligible. Ifosfamide was administered 1.5 g/m2 intravenously (IV) over 1 h and cisplatin was given 20 mg/m2 over 15 min followed by mesna 120 mg/m2 IV bolus, then 1.5 g/m2/24 h as a continuous infusion. Initial doses (daily × 5 every 21 days × 3 cycles) were reduced by 20% (to 4 days) for myelotoxicity.Nine of seventy-six patients enrolled were deemed ineligible and another two who did not receive protocol treatment were inevaluable. Of the 65 evaluable patients, median age was 65 years; 50 patients (77%) were stage I and 15 (23%) were stage II. PFS and OS, respectively, were 69% and 82% at 24 months, and 54% and 52% at 84 months. Overall 5-year survival was 62%. Leukopenia was the most commonly reported, but manageable, toxicity.Adjuvant ifosfamide and cisplatin after primary surgery for stage I or II carcinosarcoma of the uterus is tolerable. In the absence of concurrent controls, the impact on PFS and OS is unclear. Pelvic relapse remains problematic.

Effect of perioperative venous thromboembolism on survival in ovarian, primary peritoneal, and fallopian tube cancer

Objectives Venous thromboembolism (VTE) affects 15% of cancer patients and is the second leading cause of death in hospitalized cancer patients. The purpose of this study was to describe the overall survival of patients with ovarian, primary peritoneal, and fallopian tube cancers treated for VTE within 30 days of initial surgery. Methods We reviewed the medical records of all patients who developed VTE within 30 days of primary surgery for stage I–IV epithelial ovarian, tubal, or primary peritoneal cancer at our institution from 1/99 to 4/05. Standard statistical tests were used. Results Fifty-seven (10%) of 559 patients developed VTE within 30 days of initial surgery. There were no deaths from VTE within 30 days of surgery. With a median follow-up of 2.8 years (range, 0.11–7.3 years), the median overall survival for the entire cohort was 5.9 years (95% CI, 4.6-NR). The proportion of advanced-stage (III–IV) patients within the VTE group compared to the group with no VTE was higher (90% versus 72%; P = 0.0078), as was the proportion of patients with ascites compared to those with none (74% versus 54%; P = 0.0045), and the proportion of patients with residual disease > 1 cm compared to those with ≤ 1 cm (37% versus 19%; P = 0.0021). On multivariate analysis, advanced stage ( P < 0.0001), the presence of ascites ( P = 0.0210), and residual disease > 1 cm ( P < 0.0001) were significant predictors of poorer overall survival. VTE within 30 days of surgery was not found to be independently associated with overall survival (hazard ratio, 1.1; 95% CI, 0.71–1.7); P = 0.65). Conclusions Previous studies have shown that a significant number of patients undergoing primary surgery for ovarian cancer will develop postoperative VTE, especially those undergoing extensive cytoreductive procedures. In this large cohort of patients with ovarian, tubal, or primary peritoneal cancer, we found no detrimental effects of perioperative VTE on overall survival.

Influence of the Gynecologic Oncologist on the Survival of Ovarian Cancer Patients

To estimate the influence of gynecologic oncologists on the treatment and outcome of patients with ovarian cancer. Data were obtained from California Cancer Registry from 1994 to 1996. Kaplan-Meier and Cox proportional hazard methods were used for analyses. Of 1,491 patients, the median age was 65 years (range: 13-100). Only 34.1% received care by gynecologic oncologists (group A) while 65.9% were treated by others (group B). Women in group A were more affluent (P<.001), were more educated (P=.036), were classified as white-collar employees (P=.128), and lived in urban regions (P<.001) compared with group B. Patients who saw gynecologic oncologists were more likely to have surgery as their initial treatment (91.9% versus 69.1%; P<.001), present with advanced (stage III-IV) cancers (78.2% versus 70.5%; P<.001), have more grade 3 tumors (61.7% versus 39.9%; P=.048), and receive chemotherapy (90.0% versus 70.1%; P<.001). Women in group B had a fourfold higher risk of having unstaged cancers (8.0% versus 2.1%; P<.001). The 5-year disease-specific survival of group A patients was 38.6% compared with 30.3% in group B (P<.001). On multivariable analysis, early stage, lower grade, and treatment by gynecologic oncologists were independent prognostic factors for improved survival. After adjusting for surgery and chemotherapy, there was no improvement in survival associated with care by gynecologic oncologists (hazard ratio=0.90, 95% confidence interval 0.78-1.03; P=.133). In this study of 1,491 women, those who were treated by gynecologic oncologists were more likely to undergo primary staging surgery and receive chemotherapy. Stage, grade of disease, and treatment by gynecologic oncologists were important prognosticators.

The second-look operation improves survival in suboptimally debulked stage III ovarian cancer patients

In a single-institution retrospective cohort study, 230 patients were treated for stage III primary ovarian cancer and 175 became eligible for second-look operations by virtue of a complete clinical response after primary surgical cytoreduction and platinum-based combination chemotherapy. Of these, 109 underwent a second-look operation. Optimal primary cytoreduction was defined as residual disease ≤1 cm. Median follow-up was 68.3 months. Five-year survival for all the 230 stage III ovarian cancers was 43.4%. Among all eligible patients (n = 175), there was no survival difference (P = 0.67) in those having second look (57.3%, 5-year survival) versus no second look (48.7%). In those patients with optimal primary cytoreduction (n = 118), there was no survival advantage to second look (69% versus 61%, P = 0.7). However, in those with suboptimal primary cytoreduction (n = 47), 5-year survival was 36% in those having second look versus only 13% in those refusing second look (P &lt; 0.05). Multivariate analysis identified second-look surgery as the only significant independent prognostic variable affecting survival (RR = 0.321, P &lt; 0.04). Patients with suboptimal debulking at primary surgery for stage III ovarian cancer appear to achieve a survival benefit from second-look surgical procedures, presumably from the early identification and treatment of residual disease.

The second-look operation improves survival in suboptimally debulked stage III ovarian cancer patients

In a single-institution retrospective cohort study, 230 patients were treated for stage III primary ovarian cancer and 175 became eligible for second-look operations by virtue of a complete clinical response after primary surgical cytoreduction and platinum-based combination chemotherapy. Of these, 109 underwent a second-look operation. Optimal primary cytoreduction was defined as residual disease < or =1 cm. Median follow-up was 68.3 months. Five-year survival for all the 230 stage III ovarian cancers was 43.4%. Among all eligible patients (n = 175), there was no survival difference (P = 0.67) in those having second look (57.3%, 5-year survival) versus no second look (48.7%). In those patients with optimal primary cytoreduction (n = 118), there was no survival advantage to second look (69% versus 61%, P = 0.7). However, in those with suboptimal primary cytoreduction (n = 47), 5-year survival was 36% in those having second look versus only 13% in those refusing second look (P < 0.05). Multivariate analysis identified second-look surgery as the only significant independent prognostic variable affecting survival (RR = 0.321, P < 0.04). Patients with suboptimal debulking at primary surgery for stage III ovarian cancer appear to achieve a survival benefit from second-look surgical procedures, presumably from the early identification and treatment of residual disease.

Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncology Group study

Objectives To determine progression-free survival (PFS) and overall survival (OS) in women with completely resected stage I or II carcinosarcoma of the uterus treated with adjuvant ifosfamide and cisplatin, and to assess the toxicity of this regimen. Methods Eligible patients had histologically confirmed carcinosarcoma (mixed mesodermal tumor) and no postoperative radiotherapy following complete resection for clinical stage I or II disease. They were to have adequate renal, hepatic, and hematologic functions and performance status of 2 or less. Study entry was to be within 8 weeks of hysterectomy. Patients with previous chemotherapy, or other noncutaneous malignancies, were ineligible. Ifosfamide was administered 1.5 g/m 2 intravenously (IV) over 1 h and cisplatin was given 20 mg/m 2 over 15 min followed by mesna 120 mg/m 2 IV bolus, then 1.5 g/m 2/24 h as a continuous infusion. Initial doses (daily × 5 every 21 days × 3 cycles) were reduced by 20% (to 4 days) for myelotoxicity. Results Nine of seventy-six patients enrolled were deemed ineligible and another two who did not receive protocol treatment were inevaluable. Of the 65 evaluable patients, median age was 65 years; 50 patients (77%) were stage I and 15 (23%) were stage II. PFS and OS, respectively, were 69% and 82% at 24 months, and 54% and 52% at 84 months. Overall 5-year survival was 62%. Leukopenia was the most commonly reported, but manageable, toxicity. Conclusion Adjuvant ifosfamide and cisplatin after primary surgery for stage I or II carcinosarcoma of the uterus is tolerable. In the absence of concurrent controls, the impact on PFS and OS is unclear. Pelvic relapse remains problematic.

Adjuvant radiotherapy in early stage ovarian carcinoma

In a series of 228 women diagnosed with malignant ovarian tumors during the years 1980-87 radiotherapy was added as postoperative adjuvant therapy. Twenty-three cases with epithelial borderline carcinomas and 18 cases with nonepithelial tumors were excluded from the analysis. The remaining 187 cases of invasive epithelial ovarian carcinoma in FIGO stage I-II was a complete, consecutive, and total geographic series. After primary staging surgery lower abdomino-pelvic or whole abdominal radiotherapy was administered. The dose to the upper part of the abdomen was 20 Gy (fraction dose 1.0 Gy) and to the lower part and the pelvis 40 Gy (fraction dose 1.7 Gy). The patients were followed up for at least 10 years. During the follow-up 75 tumors (40%) recurred and were then treated with cisplatin-containing chemotherapy. Abdomino-pelvic (18%) and abdomino-pelvic-distant metastases (11%) were most frequent. Mean time to recurrence was 26 months. The 5-year overall survival of the complete series was 57% and the cancer-specific survival 66%. FIGO stage and tumor grade were the only independent and significant prognostic factors in a Cox multivariate analysis. Only cases in FIGO stage IA and grade 1 could be classified as low-risk cases with 5-year survival of 87%. All other cases showed a significantly worse prognosis and should be classified as intermediate or high-risk cases. Early radiation reactions were frequent (80%) but of little clinical significance. In 21 cases (11%) late radiation reactions were recorded. In 8 cases (4%) the reactions were regarded as severe and required surgical intervention or disabled the patient significantly. The results compare well with others reported in the literature.

Long-term results of primary surgery for stage I small cell lung cancer: Rocco G, Tondini M, Massera F, Rossi G, Della Pono C, Robustellini M et al. Division of Thoracic Surgery, E. Morelli Regional Hospital, Via Zubiani 33, 23039 Sondalo. Radiol Oncol 1994;28:365–368

Long-term results of primary surgery for stage I small cell lung cancer: Rocco G, Tondini M, Massera F, Rossi G, Della Pono C, Robustellini M et al. Division of Thoracic Surgery, E. Morelli Regional Hospital, Via Zubiani 33, 23039 Sondalo. Radiol Oncol 1994;28:365–368