Stage IIIC endometrioid corpus cancer includes distinct subgroups

OBJECTIVE: Because stage IIIC corpus cancer is a heterogeneous substage, the outcomes of patients with stage IIIC disease were assessed according to the extent of extrauterine disease. METHODS: From 1984 through 1993, 51 patients with surgical stage IIIC corpus cancer were treated at our institution; 5 patients had tumors with nonendometrioid histologic features and were excluded from the analyses. Of the 46 patients with endometrioid carcinoma, 22 had lymph nodes as the only site of extrauterine disease (stage IIIC(0)) and 24 also had peritoneal cytologic, uterine serosal, adnexal, or vaginal involvement or a combination of these (stage IIIC(ab)). The mean number of lymph nodes removed was 18 pelvic and 8 aortic nodes. Median follow-up for surviving patients was 84 months. RESULTS: Patients with stage IIIC(0) cancer had a 5-year cause-specific survival (CSS) of 72% and a 5-year recurrence-free survival (RFS) of 68%, and those with stage IIIC(ab) had a CSS of 33% and an RFS of 25% (P < 0.01). Of the 22 patients with stage IIIC(0) endometrioid cancer, 21 had adjuvant radiotherapy (1 also received chemotherapy) and 1 was not treated. Relapse occurred in 7 (32%) patients, with only 1 having an initial failure component outside the node-bearing areas (lung). Of the 24 patients with stage IIIC(ab) cancer, 16 received adjuvant radiotherapy (1 had concomitant chemotherapy), 2 had chemotherapy, 4 had hormonal therapy, and 2 were not treated. We observed 16 recurrences (67%). Of the 14 patients with known initial sites of failure, 9 had an extranodal failure component. CONCLUSION: Assessment of CSS, RFS, and sites of relapse suggests that FIGO surgical stage IIIC endometrioid corpus cancer includes two distinct and readily separable subgroups: (1) stage IIIC(0), nodal involvement only, and (2) stage IIIC(ab), nodal plus cytologic, uterine serosal, adnexal, or vaginal involvement, or a combination of these. Our results also suggest that different treatment strategies are needed for these subgroups.     

Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer

Objective

Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy.

Methods

Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests.

Results

Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P = 0.018).

Conclusions

Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.     

The investigation of the factors affecting retroperitoneal lymph node metastasis in stage IIIC and IV epithelial ovarian cancer

Introduction  

The appropriate management of advanced ovarian cancer has been controversial in recent years. Lymphatic node involvement is known one of the most important prognostic factors in epithelial ovarian carcinomas. On the other hand in patients with advanced ovarian cancer involving the upper abdomen (with/without lymph node involvement) the evaluation of pelvic and para-aortic lymph nodes does not contribute to the staging and more importantly it does not improve overall-survival.     

Improved survival for stage IIIC ovarian cancer patients treated at the Norwegian Radium Hospital between 1984 and 2001

BACKGROUND: The aim of this study was to evaluate the treatment of FIGO Stage IIIC patients who were primarily treated completely or partially at the Norwegian Radium Hospital (NRH) during a 15-year period in order to discover possibilities for improvement of prognosis of advanced ovarian cancer. MATERIALS AND METHOD: A retrospective study based on record information from all patients with epithelial ovarian cancer Stage IIIC treated at NRH from 1985-2000, in total 776 patients. RESULTS: We found age, amount of residual tumour after surgery for primary treatment and type of chemotherapy to be the most significant prognostic factors for overall survival. During the last 5-year period primary surgery was increasingly centralised, and surgery was improved with lymph node staging and use of paclitaxel. Survival was significantly better during the last 5-year period and after macroscopic radical surgery. Also progression-free survival was better with no macroscopic tumour remaining. INTERPRETATION: Improved survival during the last 5-year period is partly attributed to improved surgery and partly to the addition of paclitaxel. We believe that further centralisation of primary surgery for advanced ovarian cancer can contribute to a better prognosis.     

Survival after multimodality treatment for stage IIIC endometrial cancer

OBJECTIVE: Our purpose was to review our results of multimodality treatment of lymph node metastasis in endometrial cancer (stage IIIC). STUDY DESIGN: All patients underwent surgical staging for endometrial cancer with complete pelvic and aortic lymphadenectomy. All macroscopic nodal metastases were resected. Patients with microscopic nodal metastasis received adjuvant teletherapy, whereas those with macroscopic nodal metastasis received chemotherapy (carboplatin AUC 5 and paclitaxel 135 mg/m2 every 3 weeks for 6 courses) followed by teletherapy. RESULTS: Twenty-one patients had stage IIIC disease, and one had stage IVB (inguinal nodal metastasis). Sixty-four percent of tumors were poorly differentiated. Fifty-five percent of patients had pelvic nodal metastasis only and 41% had macroscopic nodal metastasis. At a median follow-up of 3.8 years, 32% of patients had recurrence, all extrapelvic. Overall mean survival was 48 months and progression-free survival was 40 months. Overall survival for microscopic nodal metastasis was >60 months versus 35 months for macroscopic metastasis. Overall survival for pelvic nodal metastasis was 53 months versus 42 months for aorticinguinal metastasis. There were no complications from lymphadenectomy, a 22% chemotherapeutic toxicity, and a 14% radiation toxicity. CONCLUSION: Our surgical, chemotherapeutic, and radiation treatment protocol for stage IIIC endometrial cancer produced minimal toxicity and good survival.     

Description of an endometrioid ovarian cancer cell line

A human cell line, designated L-1, has been established from the ascites of an untreated patient with stage IV (FIGO) endometrioid ovarian cancer. This cell line initially grew uninterupted for 6 months without fibroblast contamination and contact inhibition, and has been subcultured weekly for the past 7 years. L-1 does not contain steroid hormone receptors nor does it demonstrate the presence of oncofetal antigens by immunohistochemical techniques. The doubling time of L-1 is 11.8 hr. Flow cytometric analysis reveals an aneuploid DNA peak, and an abnormal karyotype demonstrates hyperdiploidy, translocations, and deletions. Morphology, growth patterns, cytogenetic analysis, and other features of L-1 are characterized.     

Analysis of racial disparities in stage IIIC epithelial ovarian cancer care and outcomes in a tertiary gynecologic oncology referral center

Objective

To examine disparities in delivery of care and survival according to racial classification among White and African-American women with Stage IIIC epithelial ovarian cancer undergoing initial treatment in a tertiary referral center setting.

Methods

All consecutive patients diagnosed with Stage IIIC epithelial ovarian cancer between 1/1/95 and 12/31/08 were identified and clinic-pathologic variables retrospectively collected. Differences in initial treatment paradigm, surgical and adjuvant therapy, and overall survival according to racial classification were assessed by univariate and multivariate analyses.

Results

A total of 405 patients (White, n = 366; African-American, n = 39) were identified. There were no significant differences according to racial classification in age, CA125, ASA class, histology, tumor grade, the frequency of initial surgery (90.4% vs 82.1%, p = 0.06), optimal residual disease (73.0% vs 69.2%, p = 0.28), no gross residual disease (51.4% vs 53.8%, p = 0.49), and platinum-taxane chemotherapy (88.3% vs 87.2%, p = 0.55). The median overall survival for White patients was 50.5 months (95%CI = 43.2-57.9 months), compared to 47.0 (95%CI = 36.2-57.8) months for African-Americans (p = 0.57). On multivariate analysis, age, tumor grade 3, serum albumin < 3.0 g/dl, platinum-based chemotherapy, and no gross residual disease were independently associated with overall survival, while African-American race was not (HR = 1.06, 95%CI = 0.61-1.79).

Conclusions

Among women undergoing initial treatment for ovarian cancer at a tertiary referral center, African-American patients were as likely as White patients to undergo cytoreductive surgery, be left with minimal post-surgical residual disease, and receive appropriate chemotherapy. With equal access to gynecologic oncology care and multidisciplinary cancer resources, the survival disparities according to race observed in population-based studies are largely mitigated.     

Solitary intracranial metastases from primary endometrioid ovarian cancer

A rare case of involvement of the Central Nervous System characterized by brain and subsequent cerebellar metastases without abdomino-pelvic spread is reported. The patient was treated by craniotomy plus external radiation to the brain. Subsequently, Carboplatin-based chemotherapy was started when paraaortic lymph-nodes involvement has been detected. Follow-up is uneventful after clinical complete remission. Received: 17 February 1997 / Accepted: 2 June 1997     

Resection of lymph node metastases influences survival in stage IIIC endometrial cancer

OBJECTIVE: Surgical staging of endometrial cancer identifies those patients with microscopic metastatic disease most likely to benefit from adjuvant therapy and may also confer therapeutic benefit. Our objective was to compare survival of patients who underwent resection of grossly positive lymph nodes (LN) to those with microscopically positive LN. METHODS: Patients had stage IIIC endometrial cancer with pelvic and/or aortic LN metastases and underwent surgery between 1973 and 2002. Exclusion criteria included pre-surgical radiation and second primary cancer. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Mean age of 96 patients with stage IIIC endometrial cancer was 64. There were 45 cases with microscopic LN involvement and 51 with grossly enlarged LN. Overall, 41% had disease in aortic LN, which in 18% represented isolated aortic LN metastasis. Adjuvant therapies were given to 92% of patients (85% radiotherapy, 10% chemotherapy, 10% progestins). Among those with grossly involved LN, 86% were completely resected. Five-year disease-specific survival (DSS) was 63% in 45 patients with microscopic metastatic disease compared to 50% in 44 patients with grossly positive LN completely resected and 43% in 7 with residual macroscopic disease. In multivariable analyses, gross nodal disease not debulked (HR=6.85, P=0.009), serosal/adnexal involvement (HR=2.24, P=0.036), diagnosis prior to 1989 (HR=4.33, P<0.001), older age (HR=1.09, P<0.001), and >2 positive lymph nodes (HR=3.12, P=0.007) were associated with lower DSS. CONCLUSION: Grossly involved LN can often be completely resected in patients with stage IIIC endometrial cancer. These retrospective data provide evidence suggestive of a therapeutic benefit for lymphadenectomy in endometrial cancer.     

Prognostic analysis for Chinese patients with stage I ovarian endometrioid carcinoma

Background

This study aimed to identify the clinical and pathological characteristics and the possible prognostic factors for Chinese patients with early-stage ovarian endometrioid carcinoma.

Methods

The present study reviewed the medical records of patients who received initial treatment and a postoperative pathological diagnosis of ovarian endometrioid carcinoma at our center. In all, 78 patients had stage I ovarian endometrioid carcinoma.

Results

In this series, the 5-year overall survival rate and 5-year disease-free survival (DFS) rates of patients with stage I ovarian endometrioid carcinoma was 98.7% and 87.2%, respectively. Univariate analysis showed the factors that influence the DFS rates include menopausal status, FIGO stage, histological grade, lymphadenectomy, cytology of ascites. Multivariate analysis showed that grade 3 and lymphadenectomy were the independent prognostic factors of DFS for Stage I ovarian endometrioid carcinoma (P = 0.0259, 0.0276 respectively). However, the coexisting endometriosis, concomitant endometrial disorders, dissection of para-aortic lymph node and more courses of thermotherapy had no influence on DFS. Besides, it was found that 19.3% of patients in this series had synchronous early stage and well-to-moderate differentiated endometrial carcinoma.

Conclusions

Grade 3 and lymphadenectomy were indicated as the independent factors of DFS for stage I patients with ovarian endometrioid carcinoma. The endometrial changes should be considered seriously when fertility-sparing surgery was planned.

     

Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: A histologic dichotomy

Background

Treatment failures in stage IIIC endometrial carcinoma (EC) are predominantly due to occult extrapelvic metastases (EPM). The impact of chemotherapy on occult EPM was investigated according to grade (G), G1/2EC vs G3EC.

Methods

All surgical-stage IIIC EC cases from January 1, 1999, through December 31, 2008, from Mayo Clinic were included. Patient-, disease-, and treatment-specific risk factors were assessed for association with overall survival, cause-specific survival, and extrapelvic disease-free survival (DFS) using Cox proportional hazards regression.

Results

109 cases met criteria, with 92 (84%) having systematic lymphadenectomy (> 10 pelvic and > 5 paraaortic lymph nodes resected). In patients with documented recurrence sites, occult EPM accounted for 88%. Among G1/2EC cases (n = 48), the sole independent predictor of extrapelvic DFS was grade 2 histology (hazard ratio [HR], 0.28; 95% CI, 0.08–0.91; P = .03) while receipt of adjuvant chemotherapy approached significance (HR 0.13; 95% CI, 0.02, 1.01; P = .0511). The 5-year extrapelvic DFS with and without adjuvant chemotherapy was 93% and 54%, respectively (log-rank, P = .02). Among G3EC (n = 61), the sole independent predictor of extrapelvic DFS was lymphovascular space involvement (HR, 2.63; 95% CI, 1.16–5.97; P = .02). Adjuvant chemotherapy did not affect occult EPM in G3EC; the 5-year extrapelvic DFS for G3EC with and without adjuvant chemotherapy was 43% and 42%, respectively (log-rank, P = .91).

Conclusions

Chemotherapy improves extrapelvic DFS for stage IIIC G1/2EC but not stage IIIC G3EC. Future efforts should focus on prospectively assessing the impact of chemotherapy on DFS in G3EC and developing innovative phase I and II trials of novel systemic therapies for advanced G3EC.     

Adjuvant treatment for stage IIIC endometrial cancer: options and controversies

Endometrial cancer is the most common gynecologic malignancy. Locally advanced and high risk endometrial cancer encompasses a heterogeneous group of patients and optimal treatment for various sub-groups of these patients remains controversial. Stage IIIC is the most common sub-stage of patients with locally advanced endometrial carcinoma. This article reviews retrospective and prospective data of various adjuvant treatment approaches involving chemotherapy, radiation therapy, or combined modality therapy, including the recently proposed “sandwich” regimens that have yielded encouraging results. Areas of controversy are also discussed to assist clinicians in identifying the most effective adjuvant treatment regimens for patients with locally advanced disease. On-going randomized trials are briefly discussed.     

The impact of ultra-radical surgery in the management of patients with stage IIIC and IV epithelial ovarian,fallopian tube,and peritoneal cancer

Objective

The aim of this study is to estimate the percentage of patients with metastatic ovarian, fallopian tube, and primary peritoneal cancer requiring ultra-radical surgery to achieve cytoreduction to less than 1 cm (optimal) or no macroscopic residual disease (complete).

Methods

Perioperative data were collected prospectively on consecutive patients undergoing elective cytoreductive surgery for metastatic epithelial ovarian, fallopian tube, or primary peritoneal cancer at the Norfolk and Norwich University Hospital, a tertiary referral cancer centre in the United Kingdom from November 2012 to June 2016.

Results

Over a 42-month period, 135 consecutive patients underwent cytoreductive surgery for stage IIIC and IV ovarian, fallopian tube, or primary peritoneal cancer. The median age of the patients was 69 years. 47.4% of the patients underwent diaphragmatic peritonectomy and/or resection, 20% underwent splenectomy, 14.1% had excision of disease from porta hepatis and celiac axis, and 5.2% of the patients had gastrectomy. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54.1 and 34.1% of the cases, respectively. Without incorporating surgical procedures in the upper abdomen (‘ultra-radical’), the combined rate of complete and optimal cytoreduction would be only 33.3%.

Conclusions

Up to 50.4% of the patients in this study required at least one surgical procedure classified as ultra-radical, emphasizing the importance of cytoreductive surgery in the upper abdomen in management of women with stage IIIC and IV ovarian, fallopian tube, and primary peritoneal cancer.

     

Spontaneous regression in recurrent epithelial ovarian cancer

Background Although spontaneous regression has been reported in several cancers, it is generally believed that this rare phenomenon does not occur in epithelial ovarian cancer. Case We presented a stage IV epithelial ovarian cancer patient with long-term disease-free survival after palliative local irradiation alone against recurrence. The recurrent supraclavicular lymph node was almost completely necrotic, and the swelling of the para-aortic lymph node spontaneously regressed. Conclusion The histologic features and unexpected clinical course in this patient strongly suggest that spontaneous regression occurred in recurrent epithelial ovarian cancer.     

A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer

ObjectiveTo determine if there is an advantage to combination chemotherapy and radiation for optimally resected stage IIIC endometrial cancer (EC).MethodsA multicenter retrospective analysis of patients with EC from 1991 to 2008 was conducted. Inclusion criteria were lymph node assessment and optimally resected disease. Recurrence-free (RFS) and overall survival (OS) were analyzed using Kaplan–Meier method and Cox proportional hazards model.Results265 patients with optimally resected stage IIIC EC were identified. Postoperative therapies included radiotherapy in 17% (n = 45), chemotherapy in 17% (n = 46), and both chemotherapy and radiation in 61% (n = 161). Three-year RFS was 56% for chemotherapy alone, compared to 73% for radiation alone, and 73% for combination therapy (p = 0.12). Those receiving chemotherapy alone had the worst 3-year OS (78%) compared to either radiotherapy alone (95%) or combination therapy (90%) (p = 0.005). After adjustment for stage and grade those treated with chemotherapy alone were at a 2.2 fold increased risk of recurrence (95% CI, 1.2 to 4.2; p = 0.02) and 4.0 fold increased risk of death (95% CI, 1.6 to 10.0; p = 0.004) compared to those treated with chemotherapy and radiation. In contrast there was no significant difference in RFS [HR = 1.0 (95% CI, 0.5 to 2.0; p = 0.92)] or OS [HR = 1.1 (95% CI, 0.3 to 3.6; p = 0.91)] for those treated with radiation alone compared to those treated with chemotherapy and radiation.ConclusionAdjuvant therapy with either radiation alone or chemotherapy and radiation was associated with improved outcomes for patients with optimally resected stage IIIC EC compared to those treated with chemotherapy only.     

Ovarian cancer stage IIIC. Consequences of treatment level on overall and progression-free survival

BACKGROUND: Maximum cytoreduction at primary surgery has been found to be one of the strongest prognostic factors for survival of ovarian cancer. The aim of the study was to investigate the influence of hospital level (primary vs secondary care centre), number and timing of surgery and chemotherapy on how radical the surgery was at primary treatment of epithelial ovarian cancer Stage IIIC. MATERIAL AND METHODS: A retrospective study based on record information from all patients with epithelial ovarian cancer Stage IIIC treated at the Norwegian Radium Hospital (NRH) 1985-2000, in total 776, subdivided into four groups: 1) Local primary surgery, no direct re-operation at NRH, no interval debulking; 2) local primary surgery, no direct re-operation, but interval debulking after 3-4 courses of chemotherapy at NRH; 3) local primary surgery, direct re-operation at NRH, no interval debulking; 4) primary surgery at NRH. Lymph node biopsies at re-operation in early stages and upgrading of stage where necessary were registered. RESULTS: Whether surgery was radical or not was an independent prognostic factor for overall and progression-free survival. The treatment group was an independent prognostic factor for overall, but not for progression-free survival. Group 3 had significantly the best overall and progression-free survival (p = 0.01 and 0.05). For macroscopically radical surgery both overall and progression-free survival were found significantly better for groups 3, 4 and 1 than for group 2. Most lymph node biopsies were performed during the last period and 28% were upgraded from Stage I and II to IIIC. More patients were referred for primary surgery at NRH during the last 5-year period during which overall survival and time to progression were significantly better. INTERPRETATION: Whether primary surgery is radical or not is a significant prognostic factor for survival and primary surgery is best performed by specialists in gynaecological oncology.