Molecular Updates in Prostate Cancer

A wide array of molecular markers and genomic signatures, reviewed in this article, may soon be used as adjuncts to currently established screening strategies, prognostic parameters, and early detection markers. Markers of genetic susceptibility to PCA, recurrent epigenetic and genetic alterations, including ETS gene fusions, PTEN alterations, and urine-based early detection marker PCA3, are discussed. Impact of recent genome-wide assessment on our understanding of key pathways of PCA development and progression and their potential clinical implications are highlighted.     

Functional Magnetic Resonance Imaging in Prostate Cancer

Context

Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI), dynamic contrast-enhanced MRI, and diffusion-weighted MRI emerged as promising tests in the diagnosis of prostate cancer, and they show encouraging results.

Objective

This review emphasizes different functional MRI techniques in the diagnosis of prostate cancer and includes information about their clinical value and usefulness.

Evidence acquisition

The authors searched the Medline, Embase, and Cochrane Library databases. There were no language restrictions. The last search was performed in October 2008.

Evidence synthesis

The combination of conventional MRI with functional MRI techniques is more reliable for differentiating benign and malignant prostate tissues than any other diagnostic procedure. At present, no guideline is available that outlines which technique is best in a specific clinical situation. It also remains uncertain whether improved spatial resolution and signal-to-noise ratio of 3-T MRI will improve diagnostic performance.

Conclusions

A limited number of small studies suggest that functional MRI may improve the diagnosis and staging of prostate cancer. This finding needs further confirmation in larger studies, and cost-effectiveness needs to be established.     

Molecular Pathways to Prostate Cancer

PurposeProstate cancer continues to be a prevalent disease in the United States and western countries. Advances in the fields of molecular biology and genetics coupled with new developments in biotechnology have increased our understanding of events associated with the initiation and progression of prostate cancer. We reviewed recent scientific discoveries relating to genetic predisposition, somatic alterations and epigenetic phenomena involved in the pathogenesis of prostate cancer.Materials and MethodsReports published in the scientific literature with relevance to the molecular biology, genetics and epigenetics of prostate cancer were identified using the MEDLINE data base. Particular emphasis was placed on articles that investigated the contribution of somatic alterations to prostate cancer.ResultsA multitude of genes have recently been identified that are believed to be relevant to prostate carcinogenesis. A contemporary model for prostate cancer progression should include the potential contribution of inflammation to the development of preneoplastic or neoplastic lesions. Abnormal methylation of important growth regulatory or caretaker genes represents an alternative pathway to cancer in addition to aneuploidy, loss of heterozygosity and gene mutations.ConclusionsThe identification of molecular markers specific to early and late events in prostate cancer progression is critical for the development of improved detection and prognostication strategies. While there is evidence to support the association between inflammation and prostate cancer, the exact mechanisms by which these processes occur are not well defined. The significant contribution of somatic and epigenetic defects to prostate carcinogenesis underscores the need to develop therapeutic approaches that specifically target these molecular alterations.     

Prostate Cancer Imaging with Novel PET Tracers

Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy.     

Utility of Volume Adjusted Prostate Specific Antigen Density in the Diagnosis of Prostate Cancer in Arab Men

Background: This study was undertaken to assess the utility of prostate specific antigen (PSA) and PSA density (PSAD) in discriminating between benign and malignant prostate disease in the Kuwaiti Arab population.Methods: A total of 100 consecutive patients suspected of having prostate cancer because of serum PSA > 4 ng/ml, or detection of a prostatic nodule on rectal examination were further investigated by determination of PSAD, TRUS of prostate, sexant prostatic biopsy and histological analysis to establish the correct diagnosis. Other diagnostic measures included the determination of the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. Results: Of the 100 prostate biopsies that were performed, 33 cases were confirmed to be prostate cancer and 67 were described as benign lesions comprising benign prostatic hyperplasia (BPH) with or without prostatitis. The age range for patients with prostate cancer was 42–90 years, and 52–90 years for those without prostate cancer. The mean prostate volume was 58.82 cc (range 9–177 cc) and 62.60 cc (range 15–140 cc), the mean PSA value was 36.65 ng/ml (range 5.8–200 ng/ml) and 16.49 ng/ml (range 1.4–46.0 ng/ml), while the mean PSAD was 0.92 (range 0.046–5.714) and 0.452 (range 0.034–2.294) for patients with prostate cancer and patients without prostate cancer respectively. Patients with PSA less than 4 ng/ml (3 cases) all had benign prostate lesions, and 7 cases with PSA more than 50 ng/ml all had prostate cancer and were excluded because values above 50 ng/ml have close to 100% specificity for prostate cancer. Further analysis was done on the remaining 90 cases which were patients with a PSA between 4 and 50 ng/ml. The discriminating power of serum PSA for detecting prostate cancer as estimated by the area under ROC was 0.686 while that for PSAD was 0.732. The maximum likelihood for a positive PSA was at a PSAD cut-off point of 0.32. For the PSA cut-off point of l0 ng/ml, the sensitivity was 80%, and specificity was 42.2%. For the PSAD cut-off point of 0.32, the sensitivity was 58% and the specificity 76.6%. Conclusions: Determination of PSAD is not a useful adjunct to serum PSA values in the range of 10–50 ng/ ml in our population. PSAD value less than 0.32 with PSA less than l0 ng/ml strongly suggests benign disease.     

Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer

Background

Several systemic therapeutic options exist for metastatic castrate-sensitive prostate cancer (mCSPC). Circulating tumor DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer and can influence decision-making, but remains untested in mCSPC.