Prostate Cancer

Microsatellite Instability in Prostate Cancer by PCR or Next-Generation Sequencing.

BACKGROUND: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer.

METHODS: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (> 60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system. All methods were evaluated by comparison to targeted whole gene sequencing of DNA mismatch-repair genes, and immunohistochemistry for mismatch repair genes, where available.

RESULTS: In a set of 91 prostate tumors with known mismatch repair status (29-deficient and 62-intact mismatch-repair) MSIplus had a sensitivity of 96.6% (28/29) and a specificity of 100% (62/62), MSI by Large Panel NGS had a sensitivity of 93.1% (27/29) and a specificity of 98.4% (61/62), and MSI-PCR had a sensitivity of 72.4% (21/29) and a specificity of 100% (62/62).

CONCLUSIONS: We found that the widely used 5-marker MSI-PCR panel has inferior sensitivity when applied to prostate cancer and that NGS testing with an expanded panel of markers performs well. In addition, NGS methods offer advantages over MSI-PCR, including no requirement for matched non-tumor tissue and an automated analysis pipeline with quantitative interpretation of MSI-status.

J Immunother Cancer. 2018 Apr 17 [Epub]

Jennifer A. Hempelmann, Christina M. Lockwood, Eric Q. Konnick, Michael T. Schweizer, Emmanuel S. Antonarakis, Tamara L. Lotan, Bruce Montgomery, Peter S. Nelson, Nola Klemfuss, Stephen J. Salipante and Colin C. Pritchard

1. Department of Laboratory Medicine, University of Washington, Seattle, Washington
2. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington
3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
4. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland
5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
6. VA Puget Sound Health Care System, Seattle, Washington
7. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
8. Department of Laboratory Medicine, University of Washington, Seattle, Washington

J Immunother Cancer. 2018 Apr 17;6(1):29. doi: 10.1186/s40425-018-0341-y.

Higher Serum Testosterone Levels Associated with Favorable Prognosis in Enzalutamide- and Abiraterone-Treated Castration-Resistant Prostate Cancer.

Testosterone plays a significant role in maintaining the tumor microenvironment. The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied.

Safety of SBRT in post TURP prostate cancer patients: A propensity score matched pair analysis.

To determine the genitourinary (GU) toxicity outcomes in prostate cancer patients treated with stereotactic body radiotherapy (SBRT) who have undergone a prior transurethral resection of prostate (TURP) and compare it to a similar nonTURP cohort.

Apalutamide: Emerging Therapy for Non-Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer is the second deadliest cancer in the US and the fourth most common cancer among Saudi males. Patients usually present with non-metastatic disease and treated with localized therapy.

Partial versus complete prostatectomy specimen sampling: prospective non-inferiority study for pT3a tumours and surgical margin involvement.

The importance of additional information gained by complete versus partial sampling or prostatectomy specimens is uncertain. There is sparse data on the value of complete versus partial sampling and numbers of inclusions in studies are small and retrospective.

Triple treatment of high-risk prostate cancer. A matched cohort study with up to 19 years follow-up comparing survival outcomes after triple treatment and treatment with hormones and radiotherapy.

To evaluate the efficacy of a triple treatment strategy, including surgery, on high risk prostate cancer comparing long-term survival outcome with a cohort receiving standard radiotherapy with endocrine therapy.

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy - Beyond the Abstract

The addition of concomitant hormonal therapy (HT) to postoperative radiation therapy (RT) in patients affected by biochemical relapse (BCR) is still an open question and remains controversial. Evidence from randomized clinical trials (RCTs) suggests that the combination of HT with postoperative RT improves oncologic outcomes. However, use of androgen deprivation therapy (ADT) is associated with several side effects (cardiovascular morbidity, metabolic effects, non-metastatic bone fractures, sexual dysfunction, hot flushes, fatigue, and neurologic side effects) leading to a decreased quality of life. Therefore, the potential benefit of ADT should be weighed against the associated harms. Moreover, HT duration may have a differential effect according to the clinical and pathologic characteristics of patients.

Germline Testing for Men With Prostate Cancer: Navigating an Expanding New World of Genetic Evaluation for Precision Therapy and Precision Management

Germline genetic testing is revolutionizing prostate cancer (PCA) care, with studies revealing inherited mutations (pathogenic variants) in a spectrum of cancer risk genes.1-5 Analyses from clinical cohorts of men with PCA have reported germline mutation rates of 15% to 17% regardless of stage,1,4,5 with rates of DNA repair mutations reported to be approximately 12% in men with metastatic PCA.2 Mutations in multiple genes including BRCA1, BRCA2, HOXB13, ATM, DNA mismatch repair genes, NBN, and CHEK2 confer variable estimates of risk for PCA predisposition, aggressive disease, and lifetime risk.1-5 The highest level of PCA risk has been reported for mutations in BRCA2, and HOXB13, with BRCA2 mutations associated with poor outcomes.1 Genetic testing for men with PCA is being driven increasingly by precision therapy and precision management considerations affecting oncology and urology.

The Impact of 68Ga-PSMA PET/CT and PET/MRI on the Management of Prostate Cancer.

Prostate-specific-membrane-antigen (PSMA) is a transmembrane protein with significantly increased expression in the cells and metastases of prostate carcinoma (PCa). PSMA-expression correlates with higher serum levels of prostate-specific-antigen (PSA) and a higher Gleason Score (GS).

The Tumor Immune Contexture of Prostate Cancer.

One in seven men in North America is expected to be diagnosed with prostate cancer (PCa) during their lifetime (1, 2). While a wide range of treatment options including surgery, radiation, androgen deprivation and chemotherapy have been in practice for the last few decades, there are limited treatment options for metastatic and treatment resistant disease.

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