Geneviève Bouchard-Fortier

Value of sentinel node mapping in cancer of the cervix

OBJECTIVES To compare the relative value of two methods of detection for the sentinel lymphatic nodes (SLNs): colorimetric with Isosulfan blue (ISB) and radio-isotopic with Technetium-99 (Tc99), and to evaluate the concept of the SLN mapping applied to cervical cancer. METHODS From October 2000 to December 2006, radical surgery was planned in 211 patients who presented early-stage cancer of the cervix. Both ISB and Tc99 were used to detect the SLNs. In all cases, we proceeded with laparoscopy for the identification and removal of the SLNs, followed by a complete pelvic lymphadenectomy with or without para-aortic node sampling. The SLNs were sent for frozen section (1 level) and were ultra-staged (6 levels) for final pathology. Detection rate, sensitivity and negative predictive value (NPV) were calculated. RESULTS Among the 211 patients, ISB (n=152) identified at least 1 SLN in 92.8% of the cases. With Tc99 (n=166), the detection rate of SLN increased to 96.9%. When both techniques were used together (n=107), Tc99 was significantly better than ISB by 7.8% (p=0.0094) and at least 1 SLN (hot and/or blue) was found in 99.1% of the cases. In 16.7% of patients, a SLN was located in aberrant sites, including 3.8% in the para-aortic area. Thirty-three out of the 211 patients (15.6%) had lymph node metastases. When considering only the 181 patients with bilateral SLNs identified, the NPV of SLN is 100% after ultra staging on final pathology and 94.2% on frozen section (FS). CONCLUSION Sentinel node mapping is feasible using laparoscopy. The radio-isotopic technique adds significantly to the rate of detection. The main benefits of SLN mapping in cervical cancer are the detection of micro-metastases on ultra staging which might be missed on routine pathological evaluation, and identification of aberrant drainage sites. However, the current frozen section techniques lack sensitivity to identify very small metastases and need refinement. SLN mapping should become the standard of care in the modern management of cervical cancer and complete pelvic lymphadenectomy could be avoided when bilateral SLNs are detected in patients with lesions less than 2 cm.

Is venous thromboprophylaxis necessary in patients undergoing minimally invasive surgery for a gynecologic malignancy

OBJECTIVES Current recommendations for the use of venous thromboprophylaxis in patients undergoing minimally invasive surgery (MIS) for a gynecologic malignancy are derived from patients undergoing open surgery. Our objective was to determine the 30-day prevalence of symptomatic venous thromboembolism (VTE) after laparoscopic gynecologic oncology procedures in patients who received no thromboprophylaxis. METHODS Between January 2006 and September 2013, women who underwent MIS for endometrial, cervical or ovarian cancer at a single institution were included. Data on patient demographics, diagnosis, comorbidities, perioperative characteristics, use of thromboprophylaxis, and diagnosis of VTE were collected retrospectively. RESULTS Of the 419 patients who underwent MIS for a gynecologic cancer, 352 (84%) received no VTE prophylaxis. At least a total laparoscopic hysterectomy (simple or radical) or pelvic lymph node dissection was performed in 95% of these patients. The median length of surgery was 137 min and 95% of patients were discharged home within 1 day of surgery. The rate of VTE in the 352 untreated patients was 0.57% (1 pulmonary embolism and 1 deep vein thrombosis). There were no VTE diagnosed within 30 days of surgery in the 67 patients who received anticoagulant thromboprophylaxis. CONCLUSION The rate of VTE is low in patients undergoing minimally invasive surgery for a gynecologic malignancy despite no VTE prophylaxis. The benefits of routine use of VTE prophylaxis in this population are questionable.

Non-radical surgery for small early-stage cervical cancer. Is it time?

OBJECTIVES Non-radical surgery has been proposed in women with early-stage cervical cancer to reduce morbidity. Our objective was to evaluate the outcomes of women with early-stage cervical cancer treated with non-radical surgery. METHODS Between March 1991 and July 2013, 51 women with early-stage cervical cancer underwent simple hysterectomy or cone biopsy. All patients had assessment of pelvic lymph nodes. Patient demographics, stage, perioperative complications, pathology findings and disease-free interval were collected prospectively. RESULTS Twenty-six women had squamous cell carcinoma (SCC), 22 adenocarcinoma (AC) and 3 adenosquamous (AS) carcinoma. Thirty women were FIGO stage 1A1, 8 women IA2, and 13 women 1B1. Twenty-two (43%) and 29 (57%) women underwent simple hysterectomy and cone biopsy respectively. Median measurable tumor size was 10mm (range 2-11), and median depth of invasion was 2.0mm (range 0.1-12 mm). Lymphovascular space invasion (LVSI) was present in 18 women (35%). Surgical margins were negative in all women. Two women received adjuvant chemoradiation (one had deep stromal invasion with LVSI, and one had two micrometastases to pelvic nodes). Forty-nine women (96%) had their Foley catheter removed on the day of surgery or post-operative day 1. No intraoperative or postoperative complications occurred and the median blood loss was 100ml. Median follow-up was 21 months (range 1-112). None of the 51 women developed a recurrence during follow-up (95% CI: 0-6%). CONCLUSION Non-radical surgery in appropriately selected early-stage cervical cancer patients results in a low complication rate and excellent oncologic outcomes. This approach seems to be a reasonable option in well-selected patients.

A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer

OBJECTIVES Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC. METHODS Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves. RESULTS Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4 cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs. 1.6%, p=0.033), grade 3 neuropathy (7.8% vs. 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs. 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups. CONCLUSION IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.

Uterine Clear Cell Carcinoma: Does Adjuvant Chemotherapy Improve Outcomes?

Objectives Women with uterine clear cell carcinoma (UCCC) are at high risk of relapse. Adjuvant chemotherapy (CT) is often recommended, although its effectiveness remains controversial. Our objective was to evaluate treatment-related outcomes of patients with UCCC, particularly those treated with adjuvant CT. Methods In this retrospective cohort study, patients diagnosed with UCCC at 2 academic cancer centers from 2000 to 2014 were included. Clinical, surgical, and pathological data were collected. Survival estimates were obtained using the Kaplan-Meier method and compared by log rank test. Multivariable analysis was used to determine the effect of CT and radiation therapy (RT) on overall survival (OS) and progression-free survival (PFS). Results We included 146 patients with UCCC, with a median follow-up of 27 months (range, 1–160). Ninety-five (65%) patients presented with stage I to II disease and 51 (35%) with stage III to IV disease. Forty-six percent of patients with clinical stage I were upstaged after surgery: 29% were upstaged to stages III and IV. Thirty-one percent of patients with early-stage disease and 70% with advanced-stage received CT. Among recurrences, the majority had distant relapse in both early-stage (61.5%) and advanced-stage (96.3%) diseases. In both patients with early-stage and advanced-stage diseases, adjuvant CT did not improve OS or PFS. On multivariate analysis, CT was not a significant factor associated with improved PFS (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.69–2.71; P = 0.37) or OS (HR, 0.58; 95% CI, 0.24–1.38; P = 0.22), whereas RT was associated with improved PFS (HR, 0.51; 95% CI, 0.29–0.90; P = 0.02) and OS (HR, 0.19; 95% CI, 0.09–0.42; P < 0.001). Conclusions The high rate of upstaging after surgery highlights the importance of lymph node assessment. The high rate of distant recurrence questions the effectiveness of current CT regimens and warrants the development of novel systemic approaches. The role of adjuvant RT deserves further study.

Management of abnormal cervical cytology screening in adolescent and young women in a canadian colposcopy centre: a descriptive analysis.

OBJECTIVE To describe and analyze the management of young women referred for colposcopy at a Canadian comprehensive cancer centre for evaluation of atypical squamous intraepithelial lesion of unknown significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS We conducted a retrospective descriptive study by searching the eCancerCare Colposcopy Database at our centre for 15- to 29-year-old females with referral cytology of ASC-US and LSIL who were seen between January 2000 and January 2009. Women in three age cohorts (15 to 19 years, 20 to 24 years, and 25 to 29 years) were reviewed for risk factors and relevant medical history, cytology and histology results, treatment, and follow-up visits. RESULTS A total of 407 women met the entry criteria, with 36 women in the group aged 15 to 19, 173 in the group aged 20 to 24, and 198 in the group aged 25 to 29. Ten excisional procedures were performed among the 36 participants in the group aged 15 to 19, with normal histology found in two (20%), low-grade cervical intraepithelial neoplasia (CIN) in four (40%), and high-grade CIN in four (40%). An excisional procedure was performed in 52 of 173 participants in the group aged 20 to 24, with normal histology in 15%, low-grade CIN in 37%, and high-grade CIN in 48%. Among the group aged 25 to 29, 74 of 198 participants had an excisional procedure, with normal histology in 12%, low-grade CIN in 27%, high-grade CIN in 59%, and microinvasive squamous cell carcinoma in one woman (1%). CONCLUSION Many women under the age of 25 who were referred with low-grade abnormal cervical cytology underwent treatment(s) and many did not have significant pathology. One case of microinvasive cervical cancer was identified in a patient in the group aged 25 to 29 over the nine years of our study. Our results support the safety of developing a more conservative and coordinated approach to cervical cancer screening in adolescent and young women in Canada.

Who should be offered non-radical surgery for early- stage cervical cancer?

Cervical cancer is the fourth most common cancer in women worldwide [1]. The standard treatment for early-stage cervical cancer such as the International Federation of Gynecology and Obstetrics (FIGO) stage IB is radical hysterectomy combined with bilateral pelvic lymph node assessment [2]. Radical trachelectomy is a safe alternative for young women who wish to preserve fertility [3]. The 5-year survival rate is excellent, ranging from 73.4% to 97.5% [4-6]. However, those radical procedures have significant morbidity, mainly as a result of the removal of the parametria. The parametrectomy is the most challenging part of the procedure and major complications have been reported such as blood loss, bladder and rectal dysfunction, sexual dysfunction, and fistula formation [7-12]. In recent years, the value of radical hysterectomy or trachelectomy in early-stage cervical cancer has been questioned. Parametrial involvement in early-stage cervical cancer with favorable prognostic factors can be as low as 1% [13-15]. Several reports have suggested that less radical surgery such as cervical conization, simple trachelectomy or simple hysterectomy with pelvic lymph node assessment is probably sufficient in well-selected early-stage cervical cancer to achieve excellent oncologic outcomes [16-19]. Reade et al. [13] recently summarized those reports and identified 476 women with early-stage cervical cancer managed with non-radical surgery. The reported recurrence rate was 1.5% and the rate of cancer-related death was 0.5%. Although level I evidence is still missing, this report suggests that non-radical surgery is probably a safe option in low-risk early-stage cervical cancer patients.