Prostate Carcinoma, General Concepts



Prostate Carcinoma, General Concepts


Gladell P. Paner, MD

Rafael E. Jimenez, MD

Jesse K. McKenney, MD








Longitudinal TRUS shows a small, hypoechoic lesion image in the peripheral zone, confirmed as PCa by biopsy. A nodule of benign hyperplasia or infarction may also mimic PCa.






PCa shows a relatively dense, homogeneous solid area image at the postero-lateral aspect of the peripheral zone. PCa most commonly occurs at this site. Most PCas are multifocal.


TERMINOLOGY


Synonyms



  • Prostate carcinoma (PCa)


Definitions



  • Term “prostate cancer/carcinoma” has been used for varying histologic subtypes



    • Acinar adenocarcinoma and morphologic variants


    • Ductal adenocarcinoma


    • Adenosquamous and squamous cell carcinoma


    • Basaloid and adenoid cystic carcinoma


    • Small cell carcinoma


    • Sarcomatoid (spindle cell) carcinoma


  • However, ≥ 95% of PCas are acinar adenocarcinoma



    • Some authors use the term microacinar, acinar, or conventional to describe typical PCa


  • Epidemiologic, pathogenetic, and clinical features of PCas mainly based on those of acinar adenocarcinoma


EPIDEMIOLOGY


Age Range



  • Common in elderly men; low incidence in < 50 years


  • Incidence increases dramatically with age; > 75% occur in patients ≥ 65 years


  • Mortality from prostate cancer also increases with age



    • 3rd and 2nd cause of cancer death in ages 60-79 years and ages 80 years or older, respectively


    • Not one of top 5 causes of cancer mortality for ages 40-59 years


Incidence



  • 6th most common cancer in the world


  • Incidence varies in different parts of the world



    • Attributed to ethnic and environmental factors and detection rates of clinically latent tumors


  • High incidence areas include USA, Australia, and Scandinavian countries


  • In USA, prostate cancer is most common malignancy in men; 2nd most lethal after lung cancer



    • In 2009: 192,280 new cases of prostate cancer were expected in USA, and 27,360 men expected to die from disease


  • Low incidence areas include Asia and North Africa


  • Mortality rates



    • High in North America, North and West Europe, Australia, and Caribbean


    • Low in Asia and North Africa


    • Differences in mortality rates less marked than differences in incidence rates in different areas


Ethnicity Relationship



  • In USA, African-Americans have highest incidence and mortality rates, up to 70% higher than Caucasians


  • Lower rates in Asian-Americans than Caucasians


  • Rate differences in ethnic groups also documented in other regions of the world, such as Brazil and Europe


Diet



  • Strong positive association with diets rich in animal products, particularly red meat



    • Suggested to be due to heterocyclic amine content


  • Weak association with obesity



    • Healthy weight and diet low in total fat associated with lower risk for prostate cancer


    • Fruits and vegetables may have protective effect


ETIOLOGY/PATHOGENESIS


General Concepts



  • Migration studies demonstrate that immigrants from low incidence areas acquire intermediate-risk levels after migrating to high-risk areas



    • Suggests role for environmental and genetic factors


  • Well-documented familial association



    • 5-11x increased risk among men with 2 or more 1st-degree relatives with prostate cancer


  • Proposed higher risk with environmental exposures




    • Cadmium, rubber, textile, chemical, drug, fertilizer, and atomic energy industries


  • Vitamin D deficiency implicated and may explain geographic differences due to light exposure


  • Controversial association with xenotropic murine leukemia virus-related virus (XMRV)


CLINICAL IMPLICATIONS


Clinical Presentation



  • Majority of PCa in USA are clinically diagnosed in asymptomatic patients



    • Tumor detected due to early detection programs


  • Main indications for prostate biopsy



    • Increased serum PSA level


    • Abnormal digital rectal examination (DRE)



      • Palpable nodules, firmness, or asymmetry


      • Majority of prostate cancer (70-75%) arise in posterior zone, which is accessible by palpation


      • Low sensitivity and positive predictive value


      • Still considered “gold standard” in clinical staging of prostate cancer


  • When symptomatic, prostate cancer presents with signs or symptoms of advanced disease



    • Obstructive bladder symptoms



      • Transition zone cancers may present earlier


    • Pelvic pain due to local extension


    • Bone pain and tenderness, spinal cord compression, or adenopathy due to metastatic disease


    • Rarely, disseminated intravascular coagulation, nonbacterial thrombotic endocarditis, ascites, or pleural effusion


  • Paraneoplastic syndrome more common in certain carcinoma subtypes (i.e., small cell carcinoma)


  • ˜ 10% of transurethral resection of prostate (TURP) specimens for lower urinary tract obstruction contain incidental prostate cancer


Laboratory Tests



  • Prostate specific antigen (PSA)



    • Synthesized by secretory cells of normal, hyperplastic, or malignant prostatic acini and ducts


    • Increased diffusion into serum when basement membrane is breached by invasive PCa


    • Traditional cut off is 4 ng/mL, over which prostate biopsies are recommended


    • PSA serum level above 4 ng/mL has sensitivity of ~ 20% and specificity of 60-70% for PCa


    • Sensitivity in cancer detection increases with lower serum PSA cut-off


    • Modifications of measurement and interpretation used to improve sensitivity and specificity


    • PSA density



      • Serum PSA level/prostate gland volume


      • > 0.15 would prompt prostate biopsy


    • Age-specific ranges



      • Higher PSA levels permissible in older age groups (e.g., 2.5 ng/mL for men 40-49 years vs. 6.5 ng/mL for men 70-79 years)


    • PSA velocity



      • Relative change in time of PSA value


      • Increase of > 0.75 ng/mL per year would prompt prostate biopsy


    • Percentage of free PSA



      • PSA not bound to serum protease inhibitors


      • Low levels (< 10%) associated with higher risk of cancer


    • PSA levels useful in monitoring patients after therapy for prostate cancer


  • National Comprehensive Cancer Network (NCCN) 2009 guidelines



    • Perform biopsy for abnormal DRE regardless of serum PSA level


    • Consider biopsy for PSA 2.6-4 ng/mL or PSA velocity > 0.35 ng/mL/y when PSA ≤ 2.5 ng/mL



      • Also consider age, comorbidity, percent free PSA, prostate exam/size, family history, African-American race


    • Prefer biopsy when PSA 4-10 ng/mL or do free PSA when risk of biopsy &/or diagnosis and treatment outweighed by comorbid conditions



      • Perform biopsy if free PSA ≤ 10%


    • Perform biopsy when PSA >10 ng/mL


  • American Urological Association (AUA) 2009 Best Practice Policy



    • Baseline serum PSA level at 40 years old


    • No single threshold value for PSA to prompt prostate biopsy is recommended



      • Decision based primarily on PSA and DRE, but other factors should be considered


      • Consider multiple factors: Free and total PSA, age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history, and comorbidities


  • Prostatic acid phosphatase (PAP)



    • 1st serum marker used for prostate cancer


    • Low sensitivity and specificity limit its role in prostate cancer diagnosis and monitoring



      • Also elevated in prostatic hyperplasia and inflammation


  • Prostate specific membrane antigen (PSMA)



    • Most informative in hormone-resistant states, metastasis, or in tumor recurrence or progression


  • Molecular diagnostic tests



    • Currently investigational



      • Clinical utility in prostate cancer diagnosis and management still to be confirmed


    • May target PCa-associated proteins, mRNA, or DNA



      • High throughput gene expression profiling and proteinomics have identified genes and proteins specifically overexpressed in prostate cancer


    • Candidate biomarkers include



      • Human kallikrein 2, urokinase-type plasminogen activator receptor, PSMA, early prostate cancer antigen, prostate carcinoma antigen 3, AMACR, GST-κ, TMPRSS2-ERG gene fusions


    • Performed in tissues, blood, or urine samples


    • Use varying methods of detection, such as RT-PCR, ELISA, Western blot, or other techniques


    • RT-PCR extremely sensitive assay, capable of detecting 1 prostate cell in 108 nonprostate cells



      • Limits clinical utility of this assay due to possible nonspecific positivity



Natural History



  • PCa is biologically heterogeneous and some present clinically as “latent” or “quiescent” tumors



    • Latent form PCa extremely common; up to 80% of PCa in 9th decade


    • Unclear whether latent tumors are intrinsically different from clinically significant tumors


  • Natural history of nonlatent PCa highly dependent on stage at presentation


Imaging Findings

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Prostate Carcinoma, General Concepts

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