Large cribriform glands (> 0.25 mm diameter) as a predictor of adverse pathology in men with Grade Group 2 prostate cancer.

AIMS: A recent outcome-based, radical prostatectomy study defined > 0.25 mm diameter to distinguish large versus small cribriform glands, with > 0.25 mm associated with worse recurrence-free survival. This study evaluates whether identification of > 0.25 mm cribriform glands in Grade Group 2 patients at biopsy is associated with adverse pathology at radical prostatectomy. METHODS AND RESULTS: Tumours containing biopsy slides for 133 patients with Grade Group 2 prostate cancer with subsequent radical prostatectomy were re-reviewed for large cribriform glands (diameter > 0.25 mm). The primary outcome was adverse pathology (Grade Groups 3-5; stage pT3a or greater, or pN1). The secondary outcome was recurrence-free survival. Cribriform pattern was present in 52 of 133 (39%) patients; of these, 16 of 52 (31%) had large cribriform glands and 36 of 52 (69%) had only small cribriform glands. Patients with large cribriform glands had significantly more adverse pathology at radical prostatectomy compared to patients with small cribriform glands and no cribriform glands (large = 11 of 16, 69%; small = 12 of 36, 33%; no cribriform = 25 of 81, 31%; χ2 P-value 0.01). On multivariate analysis, large cribriform glands were also associated with adverse pathology, independent of age, prostate-specific antigen (PSA)/PSA density at diagnosis, year of diagnosis and biopsy cores percentage positive (global P-value 0.02). Large cribriform glands were also associated with increased CAPRA-S surgical risk score (Kruskal-Wallis P-value 0.02). CONCLUSIONS: Large cribriform glands using a diameter > 0.25 mm definition in Grade Group 2 patients on biopsy are associated with increased risk of adverse pathology at radical prostatectomy. The presence of large cribriform histology should be considered when offering active surveillance for those with Grade Group 2 disease.

Advancing Risk Assessment of Intermediate Risk Prostate Cancer Patients.

The individual risk to progression is unclear for intermediate risk prostate cancer patients. To assess their risk to progression, we examined the level of genomic instability in circulating tumor cells (CTCs) using quantitative three-dimensional (3D) telomere analysis. Data of CTCs from 65 treatment-naïve patients with biopsy-confirmed D'Amico-defined intermediate risk prostate cancer were compared to radical prostatectomy pathology results, which provided a clinical endpoint to the study and confirmed pre-operative pathology or demonstrated upgrading. Hierarchical centroid cluster analysis of 3D pre-operative CTC telomere profiling placed the patients into three subgroups with different potential risk of aggressive disease. Logistic regression modeling of the risk of progression estimated odds ratios with 95% confidence interval (CI) and separated patients into "stable" vs. "risk of aggressive" disease. The receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.77, while prostate specific antigen (PSA) (AUC of 0.59) and Gleason 3 + 4 = 7 vs. 4 + 3 = 7 (p > 0.6) were unable to predict progressive or stable disease. The data suggest that quantitative 3D telomere profiling of CTCs may be a potential tool for assessing a patient's prostate cancer pre-treatment risk.

3+4 = 6? Implications of the stratification of localised Gleason 7 prostate cancer by number and percentage of positive biopsy cores in selecting patients for active surveillance. / ¿3 + 4 = 6? Implicaciones de la estratificación del cáncer de próstata localizado Gleason 7 por número y porcentaje de cilindros positivos de biopsia en la selección de pacientes para vigilancia activa.

OBJECTIVE: To determine whether the number and percentage of positive biopsy cores identify a Gleason 3+4 prostate cancer (PC) subgroup of similar biologic behaviour to Gleason 3+3. MATERIAL AND METHOD: An observational post-radical prostatectomy study was conducted of a cohort of 799 patients with localised low-risk (n=582, Gleason 6, PSA <10ng/ml and cT1c-2a) and favourable intermediate PC (n=217, Gleason 3+4, PSA ≤10 ng/ml and pT2abc). The Gleason 3+4 tumours were stratified by number (≤3 vs.>3) and by percentage of positive cores (≤33% vs. >33%). We analysed the tumours' association with the biochemical recurrence risk (BRR) and cancer-specific mortality (CSM). We conducted various predictive models using Cox regression and estimated (C-index) and compared their predictive capacity. RESULTS: With a median follow-up of 71 months, the BRR and CSM of the patient group with Gleason 3+4 tumours and a low number (≤3) and percentage (≤33%) of positive cores were not significantly different from those of the patients with Gleason 6 tumours. At 5 and 10 years, there were no significant differences in the number of biochemical recurrences, the probability of remaining free of biochemical recurrences, the number of deaths by PC or the probability of death by PC between the 2 groups. In contrast, the patients with Gleason 3+4 tumours and more than 33% of positive cores presented more deaths by PC than the patients with Gleason 6 tumours. At 10 years, the probability of CSM was significantly greater. This subgroup of tumours showed a significantly greater BRR (RR, 1.6; P=.02) and CSM (RR, 5.8, P≤.01) compared with the Gleason 6 tumours. The model with Gleason 3+4 stratified by the percentage of positive cores significantly improved the predictive capacity of BRR and CSM. CONCLUSIONS: Fewer than 3 cores and a percentage <33% of positive cores identifies a subgroup of Gleason 3+4 tumours with biological behaviour similar to Gleason 6 tumours. At 10 years, there were no differences in BRR and CSM between the 2 groups. These results provide evidence supporting active surveillance as an alternative for Gleason 3+4 tumours and low tumour extension in biopsy.

The effect of Rapid Access Prostate Clinics on the outcomes of Gleason 7 prostate cancer: does earlier diagnosis lead to better outcomes?

INTRODUCTION: Rapid Access Prostate Clinics (RAPC) were introduced in Ireland by the National Cancer Control Programme bringing about expedited referral pathways and increased detection rates of prostate cancer. Lower Gleason (G) grade at diagnosis due to RAPC has been previously reported but grade at prostatectomy has not been assessed. The aim of this study was to assess the impact of RAPC on the outcomes of patients with G7 disease on radical prostatectomy (RP). METHODS: A retrospective analysis was carried out of all RPs performed over a 9-year period (2006-2014). Outcomes for G7 prostatectomies were compared before and after the introduction of the RAPC, with a further sub-analysis of G4 + 3 versus G3 + 4. The primary outcome was biochemical recurrence (BCR). Other outcomes were adjuvant/salvage radiotherapy, extra prostatic extension, positive surgical margins, seminal vesicle involvement and tumour stage. RESULTS: In total, 240 RPs were performed with 167 cases graded G7 (70 graded G4 + 3 and 97 graded G3 + 4). Since the introduction of RAPC the proportion of G4 + 3 compared to G3 + 4 has increased from 37.9 to 42%. There was no statistical difference in outcomes for G4 + 3 treated before and after the introduction of RAPC. G4 + 3 was associated with higher rates of BCR (24.4 vs. 0%, p < 0.0001, radiotherapy (41.1 vs. 4.8%, p < 0.0001) and worse histological features than G3 + 4. CONCLUSION: Despite the benefits in diagnosis of prostate cancer brought about by RAPC in Ireland, this has not translated to a lower grade for surgically treated patients. There has been no improvement in outcomes especially for higher grade G4 + 3 disease.

Validation of tertiary Gleason pattern 5 in Gleason score 7 prostate cancer as an independent predictor of biochemical recurrence and development of a prognostic model.

OBJECTIVE: To validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5. MATERIAL AND METHODS: We retrospectively reviewed the data from 4,146 patients with localized (pT2-3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model. RESULTS: Of the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001). CONCLUSIONS: Knowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling.