Advanced Ovarian Cancer: Primary or Interval Debulking? Five Categories of Patients in View of the Results of Randomized Trials and Tumor Biology: Primary Debulking Surgery and Interval Debulking Surgery for Advanced Ovarian Cancer.

BACKGROUND: Standard treatment of stage III and IV advanced ovarian cancer (AOC) consists of primary debulking surgery (PDS) followed by chemotherapy. Since the publication of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial, clinical practice has changed and many AOC patients are now treated with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The best option remains unclear. Ovarian cancer is a heterogenic disease. Should we use the diversity in biology of the tumor and patterns of tumor localization to better stratify patients between both approaches? METHODS: This analysis was based on results of five phase III randomized controlled trials on PDS and IDS in AOC patients, three Cochrane reviews, and four meta-analyses. RESULTS: There is still no evidence that NACT-IDS is superior to PDS. Clinical status, tumor biology, and chemosensitivity should be taken into account to individualize surgical approach. Nonserous (type 1) tumors with favorable prognosis are less chemosensitive, and omitting optimal PDS will lead to less favorable outcome. For patients with advanced serous ovarian cancer (type 2) associated with severe comorbidity or low performance status, NACT-IDS is the preferred option. CONCLUSION: We propose stratifying AOC patients into five categories according to patterns of tumor spread (reflecting the biologic behavior), response to chemotherapy, and prognosis to make a more rational decision between PDS and NACT-IDS. IMPLICATIONS FOR PRACTICE: Trial results regarding effect and timing of debulking surgery on survival of patients with advanced ovarian cancer have been inconsistent and hence difficult to interpret. This review examines all randomized trials on primary and interval debulking surgery in advanced ovarian cancer, including the results of the newly published CHORUS (chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer) trial. On the basis of findings presented in this review and in view of recent molecular data on the heterogeneity of ovarian tumors, we propose prognostic categorization for patients with advanced ovarian cancer to better distinguish those who would optimally benefit from primary debulking from those who would better benefit from interval debulking following neoadjuvant chemotherapy.

Sentinel node procedures in gynecologic cancers: an overview.

The aim of this study was to assess the value of sentinel lymph node procedures in gynecologic cancers. A systematic literature overview, using the PubMed database, was performed. In early stage vulvar, endometrial and cervical cancer, lymph node status is the most important prognostic factor. Lymphadenectomy, performed for adequate staging, is associated with high morbidity rates. Sentinel node procedures hold the promise of adequate staging with less treatment-related morbidity. Sentinel lymph node procedures in patients with early-stage vulvar cancer are associated with low recurrence rates, excellent survival, lower morbidity and shorter hospital stay compared to classical inguinal dissection. Therefore, these procedures should be the standard of care in early-stage unilateral vulvar cancer. Reports on sentinel lymph node procedures in endometrial and cervical cancer are ambiguous. The procedures in these cancers are reported in small studies only. Detection rates vary depending on the used injection sites and the used tracers. Bilateral detection rates are low and are not mentioned by default. Large controlled multi-institutional studies are necessary to evaluate the validity and the prognostic significance of the sentinel lymph node procedures in endometrial and cervical cancer.

BD-ProExC as adjunct molecular marker for improved detection of CIN2+ after HPV primary screening.

BACKGROUND AND METHODS: We investigated the efficacy of 8 cervical cancer screening strategies relative to cytology with emphasis on immunocytochemical detection of high-risk human papillomavirus (hrHPV)-induced cell transformation (BD-ProExC) as a tool of triage following primary cytology or hrHPV testing. 3,126 women were tested with BD-SurePath liquid-based cytology, hrHPV PCR genotyping and BD-ProExC immunostaining, and colposcopy verification to calculate sensitivity and positive predictive value (PPV) in detecting cervical intraepithelial neoplasia (CIN2(+)). RESULTS: Compared to cytology screening, double testing with cytology and hrHPV resulted in the same sensitivity with a significant increase in the PPV (relative PPV: 1.83). However, twice as many tests were needed. Cytology with atypical squamous cells of undetermined significance (ASC-US) triage and hrHPV testing showed comparative results to double testing requiring only a small increase in number of tests. Screening for hrHPV subtypes 16/18, and ASC-US triage with hrHPV16/18 resulted in significant reductions in sensitivity (ratio: 0.74 and 0.96, respectively). Primary hrHPV/BD-ProExC screening was significantly more sensitive (ratio: 1.63/1.33), but had a significantly lower PPV (ratio: 0.64/0.88). ASC-US triage by BD-ProExC increased the PPV (ratio: 1.90) but decreased the sensitivity (ratio: 0.96). Primary hrHPV screening followed by BD-ProExC triage, led to significant increases in sensitivity (ratio: 1.30) and PPV (ratio: 2.89), and resulted in 55% fewer referrals for colposcopy. CONCLUSIONS: From the investigated screening strategies, primary hrHPV DNA-based screening followed by BD-ProExC triage was determined to be the best screening strategy. IMPACT: Immunocytological triage could be used to perfect hrHPV primary screening.

Use of the levonorgestrel-releasing intrauterine system in breast cancer patients.

OBJECTIVE: To study the recurrence of breast cancer among patients who were using the levonorgestrel-releasing intrauterine system (LNG IUS). DESIGN: A retrospective, controlled cohort analysis. SETTING: Six Belgian hospitals. PATIENT(S): We identified 79 breast cancer patients who used the LNG IUS, and we selected a control group of 120 patients with no history of LNG IUS use and who were closely matched for age at diagnosis, tumor stage, tumor grade, and treatment modalities. Two subgroups were identified: [1] breast cancer patients who continued using the LNG IUS after diagnosis and [2] breast cancer patients who began using an LNG IUS after treatment for breast cancer. INTERVENTION(S): Patient's data were collected and survival analysis was performed. MAIN OUTCOME MEASURE(S): Breast cancer recurrence rate. RESULT(S): There was a recurrence rate of 21.5% (17/79) among LNG IUS users and of 16.6% (20/120) among the control group (adjusted hazard ratio, 1.86; 95% confidence interval, 0.86-4.00; no statistically significant difference). Subgroup analysis showed that women using the LNG IUS (n = 38) at the time of breast cancer diagnosis (and who continued its use) had a statistically significantly increased risk of recurrence (adjusted hazard ratio, 3.39; 95% confidence interval, 1.01-11.35) compared with patients in the control group. There was 47.4% (18/38) nodal involvement in this subgroup, and all patients who recurred had metastatic disease. CONCLUSION(S): Overall, we did not find an increased risk of breast cancer recurrence associated with use of the LNG-IUS. However, in a subgroup analysis of women who developed breast cancer while using an LNG IUS and who continued to use the LNG IUS, we found a higher risk of recurrence of borderline statistical significance. Additional research is needed to confirm or refute these findings.