W.S. Ham

The prognostic role of tertiary Gleason pattern 5 in a contemporary grading system for prostate cancer

BACKGROUND:Recently, a new prostate cancer (PC) grading system has been introduced, where Gleason score (GS) 7 (3+4) and GS 7 (4+3) are categorized into two separate groups. However, GS 7 with tertiary Gleason pattern 5 (TGP5) was not incorporated in the new grading system. In the present study, we validated the prognostic role of TGP5 in the new classification.METHODS:We retrospectively reviewed the records of 1396 patients with localized GS 6–8 PC (pT2-3N0M0) who underwent radical prostatectomy at our institution between 2005 and 2014. After excluding patients who received neoadjuvant or adjuvant therapy, or had incomplete pathological or follow-up data, 1229 patients were included in the final analysis. The Kaplan–Meier method was used to estimate and compare the probabilities of biochemical recurrence (BCR). Cox regression models were used to investigate associations between variables and the risk of BCR.RESULTS:Of 732 GS 7 patients, 75 (10.2%) had a TGP5. The BCR-free survival rate for men with TGP5 was significantly worse than for those without TGP5 (P<0.001). In multivariate Cox regression analyses for GS 7 PC, TGP5 was a significant predictor of BCR (hazard ratio 1.750, P=0.027). When the total cohort was stratified into four grade groups according to the new classification, group 2 with TGP5 had a BCR risk comparable to group 3, and group 3 with TGP5 behaved like group 4.CONCLUSIONS:Our study shows that TGP5 increased the BCR risk after RP in GS 7 PC. Moreover, we demonstrated that the presence of a TGP5 in GS 7 upgraded the BCR risk to one comparable with the next higher category under the new classification. These findings support incorporating TGP5 into GS 7 to aid with future risk assessment and follow-up scheduling for PC.

Prostate Cancer Prostate-specific antigen density predicts favorable pathology and biochemical recurrence in patients with intermediate-risk prostate cancer

This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence (BCR) in patients with intermediate-risk prostate cancer (IRPCa). Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy (RARP) for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score ≤6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan-Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients (18.7%) had favorable pathology after RARP. Lower quartile prostate-specific antigen density (PSAD) was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score (odds ratio, 5.42; 95% confidence interval, 1.01-28.97; P = 0.048). During a median 37.8 (interquartile range, 24.6-60.2) months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles (log rank, P = 0.003). Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP (hazard ratio, 4.641; 95% confidence interval, 1.109-19.417; P = 0.036). The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.

Abstract 5039: Comparative analysis of miRNA in hormonal refractory prostate cancer

Background: Nucleotides 2-7 within mature miRNAs, short RNA molecule of between 19 and 22, create the ‘seed region’ that specifies the specific mRNA. To date, miRNAs have been linked to the etiology, progression and prognosis of cancer. The gain or loss of specific miRNAs can function as an oncogene or tumor suppressor. Design: By using recently developed miRNA 14K array (Agilent), we designed to compare miRNA expression between HRPCa cell line (PC3) and sensitive cell line (LNCaP). As validation for target mRNA following bioinformatics, candidates were applied on the neoadjuvant bicalutamide treated radical prostatectomized specimens using immunohistochemistry. Results: Amongst 57 upregulated miRNAs (ratio >2.0), oncomirs-miRNAs that are amplified or overexpressed in PC3, includes miR-31, -27a, -23a, -9, -100, -29a, -24, let 7i, -21, -221, 29b, -222, -181a. Probable candidates for target mRNAs to each oncomir are tumor suppressor gene family, including p27, PTEN, apoptosis related genes (DAXX, PDCD4, caspase recruitment domain 10/11), ECM adhesion genes (Integrin β4, ADAMTS 7/8), SOCS 6. In 23 downregulated miRNAs (ratio>2.0), tumor suppressor miRNAs that are downregualted or deleted from chromosomes acting as tumor suppressor genes, include miR-141, -200 a/b/c, -148a, -429, -34a, -195, -99a, -203, -125b-2. Possible candidates for target mRNAs are oncogeneic family are EMT-related genes including ZEB1, cell cycle related genes (Wee1, cyclin E1, CDK6), prostate specific proteins (STEAP1, prostein), RTK family (AXL, Rab-38, Rab-9A), transcriptional factor promotion (EIF2, SOX6), mitogen activator (MAP p38), secretory protein (SDF2). Among the top-listed candidates, STEAP1, prostein, ZEB1, and cyclin E1 were relatively overexpressed in the refractory PCa to compare with regressing cancer cells. Conclusion: Complicated networks of miRNA play substantial and crucial roles in the regulation of hormonal refractory prostate cancer, predominantly by virtue of STEAP1, prostein, ZEB1, cyclin E1 overexpression, and suppression of apoptosis-related genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5039. doi:1538-7445.AM2012-5039