Sentinel lymph node (SLN) isolated tumor cells (ITCs) in otherwise stage I/II endometrioid endometrial cancer: To treat or not to treat?

OBJECTIVES: To assess associations between treatment and recurrence-free survival (RFS) among patients with isolated tumor cells (ITCs) in sentinel lymph nodes (SLN) and otherwise stage I/II endometrioid endometrial cancer (EC). METHODS: A multi-institutional retrospective study of patients with SLN ITCs (<200 cells and < 0.2 mm) was performed. Only patients with otherwise stage I/II EC, endometrioid histology, and no evidence of micro-or macrometastases were included. Univariate and multivariable Cox proportional hazard models were used to evaluate associations between treatment, tumor characteristics, and RFS. RESULTS: 175 patients were included. Median follow up time was 31 months. 39% stage IB and 12% stage II disease. 76 (43%) received no adjuvant therapy or vaginal brachytherapy only (NAT/VBT), 21 (12%) had external beam radiation (EBRT), and 78 (45%) received chemotherapy +/- radiation. Patients who received chemotherapy more often had tumors with deep myoinvasion, lymphovascular space invasion (LVSI), and higher grade. Nine (5.1%) patients recurred; 5 distant, 3 retroperitoneal, and 1 vaginal. Extra-vaginal recurrences were similar in patients with or without chemotherapy (5.2% vs 3.8%, p = 0.68). After controlling for stage, LVSI and grade, chemotherapy and EBRT were not associated with RFS (HR = 0.63, 95%CI 0.11-3.52, and HR = 0.90, 95%CI 0.22-3.61, respectively). Type of lymph node dissection and ITC detection method were not associated with RFS. CONCLUSIONS: Risk of retroperitoneal and/or distant recurrence is low (4.6%) for patients with stage I/II endometrioid EC and ITCs in SLNs regardless of treatment. Our preliminary data suggests that adjuvant therapy may not be significantly associated with RFS. However, longer follow-up time and a larger sample size are needed before definitive recommendations regarding adjuvant therapy for patients with EC and only ITCs in SLN can be made.

Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013.

BACKGROUND: We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model. RESULTS: In all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS-81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359-0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage. CONCLUSIONS: Adjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS.

Optimal (≤1 cm) but visible residual disease: is extensive debulking warranted?

OBJECTIVES: To determine if extensive upper abdominal surgery (UAS) affected overall survival (OS) in patients left with ≤ 1 cm but visible residual disease after undergoing primary cytoreductive surgery for ovarian cancer. Our secondary objective was to determine if leaving ≤ 1cm but visible residual throughout the small bowel (SB) conferred a worse prognosis. METHODS: All stage IIIB-IV ovarian cancer patients who had visible but ≤ 1 cm residual disease at time of primary cytoreductive surgery from 2001 to 2010 were identified. Extensive UAS procedures and residual SB involvement were recorded. RESULTS: The 219 patients identified with ≤1 cm but visible residual disease had a median OS of 51 months. In this cohort, 127 had extensive UAS performed, and 87 had residual disease involving the SB. Univariate OS analysis was performed. There was no significant difference in OS between patients who did or did not have extensive UAS (45 vs. 52 months, P=0.56), or between patients with or without residual SB disease (45 vs. 51 months, P=0.84). Factors that were significantly associated with OS were age, ASA score, family history, and stage. CONCLUSIONS: Patients cytoreduced to ≤ 1 cm but visible residual disease who required UAS did not have a worse OS than those who did not require UAS. OS was similar if residual disease involved the SB or not. For ovarian cancer patients with disease not amenable to complete gross resection, extensive surgery should still be considered to achieve ≤ 1 cm but visible residual disease status, including cases where the residual disease involves the SB.

Impact of incorporating an algorithm that utilizes sentinel lymph node mapping during minimally invasive procedures on the detection of stage IIIC endometrial cancer.

OBJECTIVE: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment. METHODS: Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used. RESULTS: We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0). CONCLUSIONS: The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection.

Reproductive outcomes of patients undergoing radical trachelectomy for early-stage cervical cancer.

OBJECTIVE: To report the reproductive outcomes of patients undergoing fertility-preserving radical trachelectomy (RT) for the treatment of early-stage cervical cancer. METHODS: We analyzed data from our institution's first 105 patients who underwent attempted fertility-sparing surgery with radical trachelectomy, pelvic lymphadenectomy, and cerclage from November 2001 to October 2010. RESULTS: Of the 105 patients who underwent attempted RT, 77 (73%) did not require a conversion to radical hysterectomy or postoperative treatment. The median age was 32 (range, 25-38 years). Most patients (75%) had stage IB1 disease. Sixty-six patients (63%) were nulliparous. Thirty-five women were actively attempting conception 6 months after surgery, and 23 (66%) women were successful in conceiving: there were 20 live births, 3 elective terminations, and 4 spontaneous miscarriages. Four patients had 2 pregnancies each; all delivered their second pregnancy between 32 and 36 weeks. Cerclage erosion through the vaginal wall occurred in 6 cases and was treated by transvaginal removal of protruding suture material. One of these patients experienced a second trimester miscarriage. CONCLUSIONS: The majority of women who attempted to conceive after radical trachelectomy were successful, and most of their pregnancies resulted in full-term births. Assisted reproduction played an important role in select women. Cerclage likely contributed to a post-trachelectomy uterine ability to carry a pregnancy to the third trimester. The second post-trachelectomy pregnancy appears to be at higher risk for preterm delivery than the first pregnancy.

Surgical cytoreduction in stage IV endometrioid endometrial carcinoma.

OBJECTIVE: To evaluate the role of surgical cytoreduction and the amount of residual disease in patients with newly diagnosed stage IV endometrioid endometrial carcinoma (EC). METHODS: Patients with stage IV EC of endometrioid histology who underwent surgery at our institution from 1977 to 2003 were identified. Patients with microscopic stage IV disease were excluded. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier method and compared with log-rank test. RESULTS: A total of 58 patients were identified, of which 9 (15.5%) had no gross residual (NGR) after surgery, 11 (19.0%) had residual disease ≤1 cm, 32 (55.1%) had residual disease >1 cm, and 6 (10.3%) had no cytoreduction attempted. The median PFS was 11.1 months (95% CI, 9.8-12.3) and the median OS was 19.2 months (95% CI, 8.5-29.9) for the cohort. The median PFS was 40.3 months (95% CI, 0-93.9) for patients with NGR disease, 11 months (95% CI, 9.9-12.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients who did not have attempted cytoreduction (P<0.001). The median OS was 42.2 months (95% CI, not estimable) for patients with NGR disease, 19 months (95% CI, 13.9-24.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients that did not have attempted cytoreduction (P<0.001). CONCLUSION: Though stage IV endometrioid EC has a poor prognosis, surgical cytoreduction to no gross residual disease in a highly select group of patients is associated with improved survival.

Sentinel lymph node mapping for endometrial cancer improves the detection of metastatic disease to regional lymph nodes.

OBJECTIVE: To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate. METHODS: All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC). RESULTS: Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003). CONCLUSION: Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread.

Tertiary cytoreduction in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer: an updated series.

OBJECTIVE: Surgical cytoreduction is an integral therapeutic modality for patients with epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) cancer in the primary setting. The role of surgical cytoreduction in the recurrent setting is not clearly defined and remains controversial. The objective of this study was to assess this potential survival benefit in a large cohort of patients with a long follow-up period. METHODS: We performed a retrospective chart review of all patients with recurrent EOC, FTC, or PPC who underwent tertiary cytoreduction at our institution from 2/98 to 2/08. Disease-specific survival (DSS) was calculated from the time of tertiary cytoreduction to death or last follow-up. Univariate and multivariate analyses were used to analyze outcomes and to identify potential prognostic factors. RESULTS: A total of 77 patients were identified, of which 38 (49%) have died of disease. The median time from secondary to tertiary cytoreduction was 25.7 months (range, 4.1-99.4 months). The median follow-up after tertiary cytoreduction was 28.9 months (range, 0.7-123.7 months), with a median DSS for the entire cohort of 47.7 months (95% CI, 25.5-69.9 months). On univariate analysis, residual disease after tertiary cytoreduction and TFI were found to be significant prognostic factors. On multivariate analysis, only residual disease after tertiary cytoreduction retained prognostic significance (P<0.001). CONCLUSION: Tertiary surgical cytoreduction may offer a survival benefit in a highly select group of patients with recurrent EOC, FTC, or PPC. This benefit appears to be greatest in patients in whom a complete gross resection can be achieved.

Cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with neuroendocrine tumor of the cervix: a case report and review of the literature.

We present a case of the syndrome of inappropriate antidiuretic hormone (SIADH) secondary to cisplatin therapy in a patient with advanced-stage large cell neuroendocrine carcinoma of the cervix. This occurred after the first cycle of cisplatin and then again after the second cycle. Carboplatin was substituted for cisplatin, and there were no further episodes of SIADH.

Beyond tertiary cytoreduction in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

BACKGROUND: Primary, secondary, and possibly tertiary surgical cytoreduction in patients with recurrent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) cancer appears to be associated with a survival benefit. The objective of this study was to assess if cytoreduction of recurrences after tertiary cytoreduction offers any potential benefit in these patients. METHODS: We performed a retrospective chart review of all patients with recurrent EOC, FTC, or PPC who underwent additional cytoreductive procedures after a prior tertiary cytoreduction (quaternary cytoreduction) at our institution between 1991 and 2008. Disease-specific survival (DSS) was calculated from the time of quaternary cytoreduction to last follow-up. Univariate analyses were used to analyze outcomes and to identify potential prognostic factors. RESULTS: A total of 15 patients were identified, of which 7 (47%) have died of disease. All patients had undergone prior optimal secondary and tertiary surgical cytoreductive procedures. The size of residual disease varied from 0 (in 10 cases/67%) to >1 cm (in 2 cases, 13%). Residual disease (1 cm) and number of recurrence sites (single vs multiple) were found to be significant prognostic factors on univariate analysis. CONCLUSIONS: Cytoreductive surgery beyond tertiary cytoreduction may be a reasonable option in highly select patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, especially in the setting of a single site of recurrent disease.

Small cell neuroendocrine carcinoma of the cervix: Analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy.

OBJECTIVES: To analyze progression-free (PFS) and overall survival (OS) in patients with small cell neuroendocrine carcinoma of the cervix (SCNEC), and to determine whether platinum-based combination chemotherapy is beneficial for this population. METHODS: We performed a retrospective analysis of all patients with SCNEC who were treated at our institution between 1/1990 and 2/2007. Patients were excluded if pathologic diagnosis was not confirmed at our institution. Standard statistical methods were utilized. RESULTS: Seventeen patients met inclusion criteria. The estimated 3-year PFS and OS rates for the entire group were 22% and 30%, respectively. Median time to progression was 9.1 months. Extent of disease was the only significant prognostic factor. Median OS for patients with early stage disease (IA1-IB2) was 31.2 months and 6.4 months for patients with advanced stage disease (IIB-IV, P=0.034). In the early-stage disease group, the 3-year distant recurrence-free survival rate was 83% for patients who received chemotherapy and 0% for patients who did not receive chemotherapy as part of their initial treatment (P=0.025). The estimated 3-year OS rate was 83% for patients who received and 20% for patients who did not receive chemotherapy as part of their initial treatment (P=0.36). CONCLUSION: Given the rarity of SCNEC this retrospective analysis is limited by a small number of patients. However, the natural history of this rare disease is akin to small cell lung cancer and the prognosis is poor due to the tumor's propensity for distant spread. The treatment should conform to the treatment of small cell lung cancer.