A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts.

BACKGROUND: Prostate cancer prediction tools provide quantitative guidance for doctor-patient decision-making regarding biopsy. The widely used online Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) utilized data from the 1990s based on six-core biopsies and outdated grading systems. OBJECTIVE: We prospectively gathered data from men undergoing prostate biopsy in multiple diverse North American and European institutions participating in the Prostate Biopsy Collaborative Group (PBCG) in order to build a state-of-the-art risk prediction tool. DESIGN, SETTING, AND PARTICIPANTS: We obtained data from 15 611 men undergoing 16 369 prostate biopsies during 2006-2017 at eight North American institutions for model-building and three European institutions for validation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used multinomial logistic regression to estimate the risks of high-grade prostate cancer (Gleason score ≥7) on biopsy based on clinical characteristics, including age, prostate-specific antigen, digital rectal exam, African ancestry, first-degree family history, and prior negative biopsy. We compared the PBCG model to the PCPTRC using internal cross-validation and external validation on the European cohorts. RESULTS AND LIMITATIONS: Cross-validation on the North American cohorts (5992 biopsies) yielded the PBCG model area under the receiver operating characteristic curve (AUC) as 75.5% (95% confidence interval: 74.2-76.8), a small improvement over the AUC of 72.3% (70.9-73.7) for the PCPTRC (p<0.0001). However, calibration and clinical net benefit were far superior for the PBCG model. Using a risk threshold of 10%, clinical use of the PBCG model would lead to the equivalent of 25 fewer biopsies per 1000 patients without missing any high-grade cancers. Results were similar on external validation on 10 377 European biopsies. CONCLUSIONS: The PBCG model should be used in place of the PCPTRC for prediction of prostate biopsy outcome. PATIENT SUMMARY: A contemporary risk tool for outcomes on prostate biopsy based on the routine clinical risk factors is now available for informed decision-making.

Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer.

BACKGROUND: Ovarian cancer is the major cause of death among gynecologic cancers with 75% of patients diagnosed with advanced disease, and only 20% of these patients having a survival duration of five years. Treatments blocking immune checkpoint molecules, programmed cell death (PD-1) or its ligand PD-ligand- I (PD-L1) have produced a beneficial and prolonged effect in a subgroup of these patients. However, there is debate in the literature concerning the prognostic value of the expression of these molecules in tumors, with immunotherapy responsiveness, and survival. We evaluated the immune landscape of the ovarian tumor microenvironment of patients, by measuring the impact of the expression of tumor PD-1, PD-L1 and infiltrating lymphocytes on stage and grade of tumors and survival, in a cohort of 55 patients with gynecologic malignancies. Most patients under study were diagnosed with advanced disease ovarian cancer. RESULTS: Our studies revealed that a low density of PD-1 and of PD-L1 expressing cells in tumor tissue were significantly associated with advanced disease (P = 0.028 and P = 0.033, respectively). Moreover, PD-L1 was expressed significantly more often in high grade tumors (41.5%) than in low grade tumors of patients (7.7%) (P = 0.040). The presence of CD3 or of FoxP3 infiltrating cells with PD-L1 in patient tumors did not impact the significance of the association of PD-L1 with high grade tumors (P = 0.040), and our analyses did not show an association between the presence of PD-1 or PD-L1 and survival. CONCLUSIONS: We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling.

Application of liquid-based transepithelial flexible brush cytology in the detection of high-grade laryngeal mucosal lesions.

BACKGROUND: The aim of this study was to evaluate the effectiveness of liquid-based transepithelial flexible brush cytology (LBTFBC) in the detection of high-grade laryngeal mucosal lesions. METHODS: Diagnostic accuracies of LBTFBC and flexible biopsy (FB) were compared with the gold standard of biopsy under general anaesthesia (BUA) in 49 and 46 patients, respectively. Using a flexible laryngoscope, transepithelial cytology and biopsy specimens were obtained with the aid of flexible brushes and biopsy forceps. Cytology specimens were graded and scored using a recently proposed oral cytologic grading and scoring system. RESULTS: Cytology showed 97, 29% sensitivity, 100% specificity, 97.9% accuracy, and FB disclosed 77.1% sensitivity, 100% specificity, and 82.2% accuracy when compared with BUA. The best cutoff value for discriminating reactive/mildly dysplastic lesions from high-grade dysplasias/invasive squamous cell carcinomas (SCCs) was determined as a cytologic score of 3, with sensitivity and specificity of 100%. CONCLUSION: LBTFBC is a simple office-based procedure, which in combination with the newly proposed classification scheme appears to be an accurate technique in the detection of high-grade laryngeal mucosal lesions. LBTFBC is more effective than FB owing to the enhanced range of sampling and ease of application. It effectively eliminates the need for general anaesthesia, and thus reducing theatre costs and the number of hospital admissions. LBTFBC is ideal for patients who require regular clinical examinations, where repeated biopsies may lead to significant vocal morbidity.

Is radical cystectomy mandatory in every patient with variant histology of bladder cancer.

Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068).Patients with non-muscle invasive variants of bladder cancers can be managed with intravesical immunotherapy if tumor is not bulky (>4 cm). Although progression to muscle invasive disease is more common than in conventional group and occurs in about 40% of the patients, life expectancy is similar to patients with conventional high-grade urothelial carcinomas provided that follow-up is meticulous.