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Prostate Cancer Diagnosis: Understanding Symptoms and Screening

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Prostate cancer (PC) is the most common male-related malignancy in the United States, the second most common cause of cancer-related death among US men, and the fourth most prevalent male malignancy worldwide.

Clinical aspects of PC vary widely, and two men with similar PC stage and PSA values may develop sharply different outcomes. The fact that most men are asymptomatic at diagnosis is a reflection of the tendency of PC to arise in the peripheral aspect of the prostate, distant from the urethra.

Obstructive and irritative urinary symptoms are consistent with larger-volume tumors involving the central tissue zone. Such symptoms are by no means restricted to PC and may be mimicked by such conditions as benign prostatic hyperplasia (BPH), urinary tract infection, and prostatitis. Progressive bone pain involving the spine, pelvis, or hips may herald the presence of metastases.

Currently, the most typical initial scenario is an older asymptomatic man with an elevated PSA who is found at subsequent biopsy to have an unanticipated histologic surprise in the form of PC. Fortunately, 90% of PC cases detected today are at a clinically localized stage.

PC screening tools include the PSA blood test and the digital rectal examination (DRE). Since the introduction of PSA testing in 1987, PC incidence has increased sharply, and mortality rates have trended downward.

Yet the cumulative risk/benefit comparisons for screening are not consistently persuasive due to the disturbing lack of randomized controlled trials (RCTs) demonstrating reduced mortality in screened populations. In fact, the US Preventive Services Task Force currently recommends against PSA-based screening.

In 1995, the Office of Technology Assessment concluded that available evidence indicated that PSA testing was of no proven mortality benefit. The CDC, American Cancer Society, and American Urological Association endorse testing with PSA and DRE annually in men reaching age 50 years, with earlier screening at age 40 years for black men or those with a family history of PC.

Since 90% of men with elevated PSA and normal DRE will be proven at biopsy to have disease confined to the prostate, most men can anticipate a favorable prognosis and a wide array of treatment options.

prostate cancer

PSA is a serine protease that functions to liquefy the ejaculate. The prostate gland is the predominant source of PSA in serum. Elevations of PSA occur with architectural disruption of the gland as in PC, BPH, prostatitis, prostate biopsy or massage, transurethral resection of prostate, and (transiently) ejaculation.

PC detection and treatment strategies are influenced by current scientific data, recommended therapies with narrow risk/benefit profiles, quality-of-life concerns, and personal perceptions and values prior to initiating treatment. Patient involvement in treatment choice is especially important in early-stage, low-risk PC, where WW is a viable option, especially in older men with limited life expectancy

Although evidence is conflicting, RP appears more appropriate for younger men with organ-confined malignancy and higher Gleason scores, in which case curative resection is clinically attractive for preventing disease progression, distant metastasis, and tumor recurrence in anticipation of >10 years of life expectancy. Large-scale RCTs are underway to further clarify treatment decisions for men with PC.

The Prostate, Lung, Colorectal, and Ovary study, involving 76,693 US men over the span of 13 years, and the European Randomized Screening for Prostate Cancer study, involving 182,160 men in Europe over the span of nine years, are promising and intended to further define relative mortality benefits of PC screening.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.18 Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status. It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.8 Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status.

It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Source: MPR

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