Ductal adenocarcinoma of the prostate: A systematic review and meta-analysis of incidence, presentation, prognosis, and management.

Context: Ductal adenocarcinoma (DAC) is relatively rare, but is nonetheless the second most common subtype of prostate cancer. First described in 1967, opinion is still divided regarding its biology, prognosis, and outcome. Objectives: To systematically interrogate the literature to clarify the epidemiology, diagnosis, management, progression, and survival statistics of DAC. Materials and methods: We conducted a literature search of five medical databases from inception to May 04 2020 according to PRISMA criteria using search terms "prostate ductal adenocarcinoma" OR "endometriod adenocarcinoma of prostate" and variations of each. Results: Some 114 studies were eligible for inclusion, presenting 2 907 170 prostate cancer cases, of which 5911 were DAC. [Correction added on 16 January 2021 after the first online publication: the preceding statement has been corrected in this current version.] DAC accounts for 0.17% of prostate cancer on meta-analysis (range 0.0837%-13.4%). The majority of DAC cases were admixed with predominant acinar adenocarcinoma (AAC). Median Prostate Specific Antigen at diagnosis ranged from 4.2 to 9.6 ng/mL in the case series.DAC was more likely to present as T3 (RR1.71; 95%CI 1.53-1.91) and T4 (RR7.56; 95%CI 5.19-11.01) stages, with far higher likelihood of metastatic disease (RR4.62; 95%CI 3.84-5.56; all P-values < .0001), compared to AAC. Common first treatments included surgery (radical prostatectomy (RP) or cystoprostatectomy for select cases) or radiotherapy (RT) for localized disease, and hormonal or chemo-therapy for metastatic disease. Few studies compared RP and RT modalities, and those that did present mixed findings, although cancer-specific survival rates seem worse after RP.Biochemical recurrence rates were increased with DAC compared to AAC. Additionally, DAC metastasized to unusual sites, including penile and peritoneal metastases. Where compared, all studies reported worse survival for DAC compared to AAC. Conclusion: When drawing conclusions about DAC it is important to note the heterogenous nature of the data. DAC is often diagnosed incidentally post-treatment, perhaps due to lack of a single, universally applied histopathological definition. As such, DAC is likely underreported in clinical practice and the literature. Poorer prognosis and outcomes for DAC compared to AAC merit further research into genetic composition, evolution, diagnosis, and treatment of this surprisingly common prostate cancer sub-type. Patient summary: Ductal prostate cancer is a rare but important form of prostate cancer. This review demonstrates that it tends to be more serious at detection and more likely to spread to unusual parts of the body. Overall survival is worse with this type of prostate cancer and urologists need to be aware of the presence of ductal prostate cancer to alter management decisions and follow-up.

Systematic Assessment of Tumor Purity and Its Clinical Implications.

PURPOSE: The tumor microenvironment is complex, comprising heterogeneous cellular populations. As molecular profiles are frequently generated using bulk tissue sections, they represent an admixture of multiple cell types (including immune, stromal, and cancer cells) interacting with each other. Therefore, these molecular profiles are confounded by signals emanating from many cell types. Accurate assessment of residual cancer cell fraction is crucial for parameterization and interpretation of genomic analyses, as well as for accurately interpreting the clinical properties of the tumor. MATERIALS AND METHODS: To benchmark cancer cell fraction estimation methods, 10 estimators were applied to a clinical cohort of 333 patients with prostate cancer. These methods include gold-standard multiobserver pathology estimates, as well as estimates inferred from genome, epigenome, and transcriptome data. In addition, two methods based on genomic and transcriptomic profiles were used to quantify tumor purity in 4,497 tumors across 12 cancer types. Bulk mRNA and microRNA profiles were subject to in silico deconvolution to estimate cancer cell-specific mRNA and microRNA profiles. RESULTS: We present a systematic comparison of 10 tumor purity estimation methods on a cohort of 333 prostate tumors. We quantify variation among purity estimation methods and demonstrate how this influences interpretation of clinico-genomic analyses. Our data show poor concordance between pathologic and molecular purity estimates, necessitating caution when interpreting molecular results. Limited concordance between DNA- and mRNA-derived purity estimates remained a general pan-cancer phenomenon when tested in an additional 4,497 tumors spanning 12 cancer types. CONCLUSION: The choice of tumor purity estimation method may have a profound impact on the interpretation of genomic assays. Taken together, these data highlight the need for improved assessment of tumor purity and quantitation of its influences on the molecular hallmarks of cancers.

Innovation in metabolomics to improve personalized healthcare.

Metabolomics is the systemic study of all small molecules (metabolites) and their concentration as affected by pathological and physiological alterations or environmental or other factors. Metabolic alterations represent a "window" on the complex interactions between genetic expression, enzyme activity, and metabolic reactions. Techniques, including nuclear magnetic resonance spectroscopy, mass spectrometry, Fourier-transform infrared, and Raman spectroscopy, have led to significant advances in metabolomics. The field is shifting from feasibility studies to biological and clinical applications. Fields of application range from cancer biology to stem cell research and assessment of xenobiotics and drugs in tissues and single cells. Cross-validation across high-throughput platforms has allowed findings from expression profiling to be confirmed with metabolomics. Specific genetic alterations appear to drive unique metabolic programs. These, in turn, can be used as biomarkers of genetic subtypes of prostate cancer or as discovery tools for therapeutic targeting of metabolic enzymes. Thus, metabolites in blood may serve as biomarkers of tumor state, including inferring driving oncogenes. Novel applications such as these suggest that metabolic profiling may be utilized in refining personalized medicine.

Prospective evaluation of AMACR (P504S) and basal cell markers in the assessment of routine prostate needle biopsy specimens.

Distinguishing benign prostate glands from malignant ones, based purely on morphology, on prostatic core needle biopsy specimens (PNBs) may prove difficult, particularly if the suspicious focus is small. In recent years, several immunohistochemical markers, including the basal cell cocktail (BCC), 34betaE12 and p63, and the prostate cancer (PCa) biomarker alpha-methylacyl-CoA-racemase (AMACR), have been used as adjuvants to morphology, in these diagnostically challenging cases. We prospectively address the diagnostic utility of using the BCC, in combination with the commercially available AMACR monoclonal antibody, P504S, on PNBs that required immunohistochemistry (IHC) studies to make a diagnosis. The goals of this prospective study were to assess the day-to-day practice in an academic setting, to determine how often these IHC tests were used on routine PNBs, and to establish how often a combination of the BCC and P504S were helpful in diagnosing prostate cancer. A total of 772 prospectively collected PNB cases were examined over a 7-month period. IHC staining was performed in 171 cases (22%); 123 cases were stained with the BCC in addition to the commercially available monoclonal AMACR antibody. In 86 of these 123 cases (70%), both stains contributed to the final diagnosis: PCa in 44 cases, benign in 33 cases and high-grade prostatic intraepithelial neoplasia in 9 cases. Of the remaining 37 cases (30%), 18 were called benign or PCa, based solely on appropriate staining with the BCC, with AMACR being noncontributory because the focus of interest had been cut through (12 cases), there was negative staining with AMACR (in 4 PCa cases), or there was positive staining with AMACR (in 2 benign cases showing atrophy). Nineteen of 37 cases were diagnosed as atypical small acinar proliferation. In these 19 cases either the focus had been cut through on one or both of the stains (11 cases), both AMACR and BCC failed to work (2 cases), AMACR was positive in the presence of patchy BCC staining (1 cases), AMACR was negative in the absence of BCC staining (3 cases), or despite appropriate staining the focus consisted of 1 gland and was considered too small to call carcinoma (2 cases). Additional IHC stains were performed in 171 of 772 cases; of these, 123 had sufficient material to perform both the BCC and P504S. The BCC when used in combination with AMACR rendered a diagnosis in almost 70% of cases. Using these stains in combination may be a better approach in diagnostically difficult cases as it increases the likelihood that a definitive diagnosis can be rendered while decreasing the likelihood of an equivocal diagnosis. However, a limitation of this approach is the loss of tissue in these small lesions, suggesting that combining AMACR and the BCC on a single slide would be superior to using either marker separately.