Waldo Jimenez

Sentinel lymph node biopsy vs. pelvic lymphadenectomy in early stage cervical cancer: Is it time to change the gold standard?

OBJECTIVE To compare the incidence of pelvic lymph node metastases in early stage cervical cancer patients undergoing sentinel lymph node biopsy (SLN) to a matched cohort undergoing pelvic lymphadenectomy. METHODS All patient data were entered prospectively into an ongoing cervical cancer database. Since April 2004, 87 patients with FIGO stage IA/B1 cervical cancer underwent SLN detection with identification of bilateral SLN. This cohort (cases) was compared to a matched group of patients who underwent complete pelvic lymphadenectomy (controls). The groups were matched 3:1 for tumour size (+/-5 mm), histology, depth of invasion (+/-2 mm), and presence of capillary lymphatic space invasion (CLS). Descriptive statistics were calculated for all variables of interest. The association between cases and controls and lymph node metastases was carried out using a conditional logistic regression analysis. RESULTS 81 women in the SLN cohort were matched with 1 control, 72 cases with 2 controls, and 65 cases with 3 controls. Among cases, 14 (17%) had pelvic lymph nodes metastases vs. 15 (7%) in the controls (p=0.0059, odds ratio= 2.8, 95% CI=1.3-5.9). Among the 14 cases of SLN metastases, 11 were detected by frozen section and 3 were detected on final paraffin sectioning. All were detected by H and E stains. The size of the SLN metastases ranged from less than 1 mm to 8 mm. CONCLUSIONS Sentinel lymph node biopsy in early cervical cancer is a more sensitive procedure in detecting pelvic lymph node metastases compared to complete lymphadenectomy.

Sentinel lymph node biopsy in vulvar cancer: Systematic review, meta-analysis and guideline recommendations.

OBJECTIVES Traditionally, treatment for early stage vulvar cancer has included removal of the primary tumor and inguinofemoral lymph node dissection (IFLD). Sentinel lymph node biopsy (SLNB) has been proposed as an alternative to IFLD for early stage vulvar cancer patients. The aim of this project was to systematically review and assess the potential for harms and benefits with the SLNB procedure in order to make recommendations regarding the adoption of the procedure, selection of patients and appropriate technique and procedures. METHODS A working group with expertise in gynecologic oncology and health research methodology was formed to lead the systematic review and process of guideline development. MEDLINE, Embase and The Cochrane Database of Systematic Reviews were searched for relevant articles published up to September 2014. Outcomes of interest included detection, false negative, complication and recurrence rates and indicators related to pathology. Meta-analyses were conducted where appropriate. RESULTS The evidence-base of a previously published health technology assessment was adopted. An additional search to update the HTAs evidence base located three systematic reviews, and eleven individual studies that met the inclusion criteria. According to a meta-analysis, per groin detection rate for SLNB using radiocolloid tracer and blue dye was 87% [82-92]. The false negative rate with SLNB was 6.4% [4.4-8.8], and the recurrence rates with SLNB and IFLD were 2.8% [1.5-4.4] and 1.4% [0.5-2.6], respectively. An internal and external review process elicited concerns about the necessity of performing this procedure in an appropriate organizational context. CONCLUSION SLNB is recommended for women with unifocal tumors<4 cm and clinically non-suspicious nodes in the groin, provided that specific infrastructure and human resource needs are met. Some recommendations for appropriate techniques and procedures are also provided.

Presumed previous human papillomavirus (HPV) related gynecological cancer in women diagnosed with anal cancer in the province of Ontario.

OBJECTIVE The oncogenic HPV subtypes responsible for gynecologic malignancies have also been implicated in the development of squamous cell cancer of the anus (SCAC). SCAC is more common in women, typically presenting at an older age than gynecologic cancers. The aim of this study was determine whether women diagnosed with anal cancer are more likely to have a history of HPV-related gynecological cancer as compared to a matched control group. METHODS We performed a population-based, case-control study at the Institute for Clinical Evaluative Sciences (ICES) which houses the administrative databases for all residents of the province of Ontario, Canada. All women diagnosed with SCAC between 1992 and 2005, identified using ICD-9 codes (154.2, 154.3, 154.8) for anatomic site and ICD-O codes (8070-8075, 8120, 8123, 8124) for histologic subtype, were included as cases. Up to 5 female controls, matched for age, socioeconomic status, health region and number of years enrolled in the provincial health plan, were selected for each case. The exposure of interest was previous HPV-related gynecologic cancer, specifically cervical cancer, vulvar cancer and vaginal cancer. Conditional logistic regression was performed to assess the relationship between this exposure and SCAC. RESULTS A total of 674 women with SCAC were identified whose median age was 61. Amongst the cases, there were 7 cervical, 3 vulvar and 1 vaginal cancers compared with 5 cervical, 0 vulvar and vaginal cancers in the 3264 controls. Previous HPV-related gynecological cancer (cervical, vaginal or vulvar cancer) was significantly associated with SCAC (OR: 10.5, 95% C.I.: 3.6 to 30.3). The median time between the diagnosis of anal cancer and previous cervical cancer was 20 years. CONCLUSIONS Previous HPV-related gynecological cancers are strongly associated with anal cancer and may occur decades before the anal cancer.

Cervical Cancer Prevention in Low-Resource Settings

Abstract Objective To help care providers understand the current status of cervical cancer in low-resource countries. Options The most effective and practical options for cervical screening and treatment in low-resource countries are evaluated. Outcomes Improvement in rates of prevention and early detection of cervical cancer in low-resource countries. Evidence PubMed or Medline, CINAHL, and The Cochrane Library were searched for studies published in English between January 2006 and December 2009. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). Recommendations 1.All girls 9 years old or over should have access to the cervical cancer vaccine before they become sexually active. (I-A) 2.Cervical cancer screening by visual inspection with acetic acid is suggested for low-resource settings acceptable. Cervical cytology or human papillomavirus testing may also be used when practical. (II-2B) 3.Cryotherapy is a safe, effective, and low-cost therapy that should be included in pre-invasive cervical cancer treatment. (III-B) 4.All countries should have a documented cervical cancer prevention strategy that includes public education built on existing outreach programs. (III-C) 5.Countries should define a centre or centres of excellence for the management of cervical cancer. (III-C) Because these units would serve a larger population, they would be able to identify leaders and develop their skills, and would be able to invest in costly radiation equipment. 6.All women with cervical cancer should have access to pain management. (III-C)

Laparoscopic Surgery for Endometrial Cancer: A Review

Uterine cancer is the fourth most common cancer in Canadian women, with an estimated 4200 new cases and 790 disease-related deaths in 2008. We investigated the domains that are important for further implementation of minimally invasive surgery for the management of endometrial cancer by performing a literature review to assess the available data on overall and disease-free survival in laparoscopic versus open surgery. We also investigated the influence of patient- related factors, surgical factors, quality of life, and cost implications. Among the 23 articles reviewed, five were randomized controlled trials (RCTs), four were prospective reviews, and 14 were retrospective reviews. The RCTs showed no difference in overall and disease-free survival for patients with endometrial cancer who had undergone laparoscopic hysterectomy compared with open surgery. Morbid obesity is a limiting factor for the feasibility of complete laparoscopic staging. Laparoscopy seems to decrease complications and decrease blood loss. It also shortens hospital stay, with improved short-term quality of life and cosmesis, while yielding similar lymph node counts. Overall, laparoscopy is cost-effective, because the increased operation cost of laparoscopy is offset by the shorter hospital stay and faster return to work. On the basis of currently available data, patients with endometrial cancer should be offered minimally invasive surgery as part of their treatment for endometrial cancer whenever possible.

Sentinel Lymph Node Biopsy in Vulvar Cancer: A Health Technology Assessment for the Canadian Health Care Context

OBJECTIVES Inguinofemoral lymphadenectomy for vulvar cancer is associated with a high incidence of groin wound complications and lymphedema. Sentinel lymph node biopsy (SLNB) is a morbidity-reducing alternative to lymphadenectomy. The objective of this health technology assessment was to determine the clinical effectiveness, cost-effectiveness, and organizational feasibility of SLNB in the Canadian health care system. METHODS A review of the English-language literature published from January 1992 to October 2011 was performed across five databases and six grey-literature sources. Predetermined eligibility criteria were used to select studies, and results in the clinical, economic, and organizational domains were summarized. Included studies were evaluated for methodologic quality using the Newcastle-Ottawa Scale. RESULTS Of 825 reports identified, 88 observational studies met the eligibility criteria. Overall study quality was poor, with a median Newcastle-Ottawa Scale score of 2 out of 9 stars. Across all studies, the detection rate of the sentinel lymph node was 82.2% per groin and the false-negative rate was 6.3%. The groin recurrence rate after negative SLNB was 3.6% compared with 4.3% after negative lymphadenectomy, and complications were reduced after SLNB. No economic evaluations were identified comparing SLNB to lymphadenectomy. Safe implementation of SLNB requires appropriate patient selection, detection technique, and attention to the learning curve. CONCLUSIONS Although study quality is poor, the available data suggest implementation of SLNB may be safe and feasible in Canadian centres with adequate procedural volumes, assuming that implementation includes careful patient selection, careful technique, and ongoing quality assessment. Cost-effectiveness has yet to be determined.

Management of Women with Surgically Staged 1 Uterine Papillary Serous Cancer

Objective. To review the management and outcomes of women with surgically staged 1 UPSC. Methods. We report on a case series from 2008–2010 from Hamilton Canada. We summarize the data from a literature search on surgically staged 1 UPSC. Results. There is a group women with Stage 1A UPSC with no residual disease at time of surgery who do not require adjuvant therapy. Vault recurrences appear to be lower in women who received adjuvant vault radiation. Chemotherapy appears to confer longer survival for those women with Stage 1B or 1C disease compared of those observed or who had radiation alone. Conclusion. Adjuvant therapy appears to confer benefit in certain groups of women with stage 1 UPSC. A randomized controlled study would clarify the degree of benefit.

Outcomes of Adjuvant Therapy for Stage IA Serous Endometrial Cancer

Purpose: Serous adenocarcinoma is a rare, aggressive histologic subtype of endometrial cancer with a high rate of recurrence and a poor prognosis. The optimal adjuvant treatment for early-stage patients is unclear. Our objective was to evaluate the outcomes of stage IA serous endometrial cancers only treated at a single institution and determine whether our current approach of chemotherapy plus vaginal brachytherapy (VBT) is sufficient. Methods: A retrospective chart review of our institutions pathology database, including all cases of stage IA serous endometrial carcinoma from 2000-2014 was completed. Kaplan-Meier estimates were calculated for Overall and Recurrence-Free Survival (OS and RFS); hazard ratios were calculated using Cox proportional hazards modeling for independent prognostic factors. Results: There were 63 patients with stage IA serous endometrial cancer of whom 79.4% were surgically staged. Percent RFS was 76.5% at five years while OS was 84.7% for the whole cohort. One of the 23 patients receiving VBT and chemotherapy recurred at the vagina versus four of 32 patients who were observed. Two patients in the observation group recurred in the pelvis while there were no first pelvic recurrences in the VBT and chemotherapy group (non- significant). Overall survival was 95% in the brachytherapy and chemotherapy group versus 79.6% in the observation group (non-significant). Post-operative management included observation (n=33), combination VBT and chemotherapy (n=21), or chemotherapy with or without external beam radiation therapy (EBRT) (n=9). Discussion: We report one of the largest cohorts of serous endometrial cancer stage IA patients. Our results emphasize the inferior RFS and OS of stage IA serous versus endometrioid endometrial cancer patients. While some centers continue to use EBRT for these patients, our results demonstrate low pelvic recurrence rates with radiotherapy limited to VBT, as well as the high systemic risk regardless of treatment. We advocate for combination chemotherapy and brachytherapy given the poor outcomes in these patients.