The PSA assay is the most widely used test in the diagnosis and management of prostate cancer, but it suffers from a number of limitations. PSA is a product of prostatic epithelium and is normally secreted in the semen. Although PSA screening can detect prostate cancers early in their course, studies of the natural history of the disease (so-called “watch-and-wait studies”) have confirmed that many prostate cancers are clinically insignificant, requiring no treatment, sometimes for decades. Overtreatment of these indolent cancers can cause significant morbidity, particularly erectile dysfunction and incontinence. A second limitation of PSA as a biomarker is that it is not cancer-specific. BPH, prostatitis, prostatic infarcts, instrumentation of the prostate, and ejaculation all may increase serum PSA levels. Conversely, 20% to 40% of patients with organ-confined prostate cancer have PSA values below the cutoffs that are used to identify patients who are likely to have prostate cancer.
Because of these problems, PSA assays are being reappraised as screening tests. By contrast, once cancer is diagnosed, serial measurements of PSA are of great value in assessing the response to therapy. For example, a rising PSA level after radical prostatectomy or radiotherapy for localized disease is indicative of recurrent or disseminated disease.
The most common treatments for clinically localized prostate cancer are radical prostatectomy and radiotherapy. The prognosis after radical prostatectomy is based on the pathologic stage, whether the margins of the resected specimens are free of tumor, and Gleason grade. The Gleason grade, clinical stage, and serum PSA values are important predictors of outcome after radiotherapy. Because many prostate cancers follow an indolent course, active surveillance (“watchful waiting”) is an appropriate approach for older men, patients with significant comorbidity, or even some younger men with low serum PSA values and small, low-grade cancers. Advanced metastatic carcinoma is treated by androgen deprivation, either by orchiectomy or by administration of synthetic agonists of luteinizing hormone–releasing hormone (LHRH). In addition, there are many new therapies that reduce androgen synthesis or signaling in metastatic prostate cancer. Although anti-androgen therapy induces remissions, androgen-independent clones almost invariably emerge, leading to rapid disease progression and death. As discussed earlier, these mutant clones commonly continue to express many genes that in normal prostate are androgen-dependent, suggesting that mechanisms arise to reactivate androgen signaling, even in the context of androgen deprivation therapy.
Carcinomaoftheprostateisacommoncancerofoldermenbetween65and75yearsofage.
Prostatecarcinomasrangefromindolentlesionsthatwillnevercauseharmtoaggressivefataltumors,whicharemorecommoninAfrican-Americans.
ThemostcommonacquiredmutationsinprostaticcarcinomascreateTPRSS2-ETS fusiongenesoracttoenhancePI3K/AKTsignaling,whichpromotestumorcellgrowthandsurvival.
Carcinomasoftheprostatearisemostcommonlyintheouter,peripheralzoneoftheglandandmaybepalpablebyrectalexamination.
GradingofprostatecancerbytheGleasonsystemcorrelateswithpathologicstageandprognosis.
SerumPSAmeasurementisacontroversialcancerscreeningtest,buthasclearvalueinmonitoringprogressiveorrecurrentprostatecancer.
URETER,BLADDER,ANDURETHRA
The renal pelves, ureters, bladder, and urethra are lined by specialized multi-layer transitional epithelium called urothelium. Beneath the mucosa are the lamina propria and, deeper yet, the muscularis propria (detrusor muscle), which makes up the bladder wall. Clinically significant disorders involving these organs include congenital aberrations, infectious and other inflammatory diseases, and neoplasms.