A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment.

BACKGROUND: Neoadjuvant chemotherapy before cystectomy confers a survival benefit in bladder cancer, but it has not been widely adopted since most patients do not benefit and we are at present unable to predict those that do. Since the most important predictor of recurrence after cystectomy is pathologically positive nodes, our aim was to assess techniques that define this stage for the selection of patients for neoadjuvant chemotherapy. METHODS: We developed a gene expression model (GEM) to predict the pathological node status in primary tumour tissue from three independent cohorts of patients who were clinically node negative. From a subset of transcripts detected faithfully by microarrays from both paired frozen and formalin-fixed tissues (32 pairs), we developed both the GEM and cutoffs that identified patient strata with raised risk of nodal involvement by use of two separate training cohorts (90 and 66 patients). We then assessed the GEM and cutoffs to predict node-positive disease in tissues from a phase 3 trial cohort (AUO-AB-05/95; 185 patients). FINDINGS: We developed a 20-gene GEM with an area under the curve of 0·67 (95% CI 0·60-0·75) for prediction of nodal disease at cystectomy in AUO-AB-05/95. The cutoff system identified patients with high relative risk (1·74, 95% CI 1·03-2·93) and low relative risk (0·70, 95% CI 0·51-0·96) of node-positive disease. Multivariate logistic regression showed the GEM predictor was independent of age, sex, pathological stage, and lymphovascular space invasion (coefficient 9·81, 95% CI 1·64-18·00; p=0·019). INTERPRETATION: Selecting patients for neoadjuvant chemotherapy on the basis of risk of node-positive disease has the potential to benefit high-risk patients while sparing other patients toxic effects and delay to cystectomy. FUNDING: US National Cancer Institute (R01CA143971).

Depot medroxyprogesterone acetate: a risk factor for cervical stenosis after loop electrosurgical excisional procedure management of cervical intraepithelial neoplasia?

OBJECTIVES: In our anecdotal experience and sporadically in the literature, gynecologists have observed a connection between patient's use of depot medroxyprogesterone acetate (DMPA) and increased occurrence of cervical stenosis during follow-up after loop electrosurgical excisional procedure (LEEP). We decided to formally examine this association in our clinic population. MATERIALS AND METHODS: We performed a chart review, enrolling 257 patients and tabulating data on demography, use of hormonal contraceptives, characteristics of the LEEP, and presence or absence of cervical stenosis at 1- and 6-month follow-up evaluations. Univariate tests of association between the independent variables and the dependent variable of cervical stenosis were examined via the chi and Student t tests for discrete and continuous variables, respectively. To characterize the relative importance of independent variables significantly associated with cervical stenosis, logistic regression was performed. RESULTS: Of the 257 charts reviewed, 127 patients (49.4%) completed 1 and 6 months after LEEP follow-up appointments, providing adequate data for analysis. In this population, we observed 25 cases of cervical stenosis, or an overall rate of 19.7%. Of patients using DMPA at the time of LEEP or during the follow-up period, 9 (41.0%) of 22 developed stenosis, whereas of those who did not use DMPA, 16 (15.2%) of 105 developed stenosis, indicating a significant difference (odds ratio = 3.85, 95% CI = 1.41-10.50). CONCLUSIONS: In our clinic population, use of DMPA was associated with higher rates of development of cervical stenosis, calling for larger studies of the association of DMPA in this LEEP complication.