Carcinoma of the prostate is predominantly a tumor of older men, which frequently responds to treatment when widespread and may be cured when localized. The rate of tumor growth varies from very slow to moderately rapid, and some patients may have prolonged survival even after the cancer has metastasized to distant sites, such as to bone. Since the median age at diagnosis is 72 years, many patients, especially those with localized tumor, may die of other illnesses without ever having suffered significant disability from their cancer. The approach to treatment is influenced by age and coexisting medical problems. Side effects of various forms of treatment should be considered in selecting appropriate management. Controversy exists in regard to the value of screening, the most appropriate staging evaluation, and the optimal treatment of each stage of the disease.[1] A complicating feature of any analysis of survival after treatment of prostate cancer and comparison of the various treatment strategies is that there is evidence of increasing diagnosis of nonlethal tumors as diagnostic methods have changed over time. Nonrandomized comparisons of treatments may therefore be confounded not only by patient-selection factors but also by time trends. For example, a population- based study in Sweden showed that during the period from 1960 to the late 1980s, prior to the use of prostate-specific antigen (PSA) for screening purposes, long-term relative survival rates after the diagnosis of prostate cancer improved substantially as more sensitive methods of diagnosis were introduced. This occurred despite the fact that watchful waiting or palliative hormonal treatment were the most common treatment strategies for localized prostate cancer during the entire era (fewer than 150 radical prostatectomies per year were performed in Sweden during the late 1980s). The investigators estimated that if all cancers diagnosed in 1960 to 1964 were of the lethal variety, then at least one-third of cancers diagnosed in 1980 to 1984 were of the nonlethal variety.[2][Level of evidence: 3iB] With the advent of PSA screening, the ability to diagnose nonlethal prostate cancers may increase further.

The issue of screening asymptomatic men for prostate cancer with digital rectal examination (DRE), PSA, and/or ultrasound is controversial.[3,4] Serum PSA and transrectal ultrasound are more sensitive and will increase the diagnostic yield of prostate cancer when used in combination with rectal examination. (Refer to the PDQ summary on screening for prostate cancer for a discussion of this issue.) However, they are also associated with high false positive rates and may identify some tumors that will not threaten the patient's health.[5-7] Morbidity associated with work-up and treatment of such tumors, as well as considerable cost beyond a routine DRE complicate the issue. Furthermore, because a high percentage of tumors identified by PSA screening alone have spread outside the prostate, PSA screening may not improve life expectancy. In any case, the clinician who uses PSA for the detection of prostate cancer should be aware that there is no uniform standard, so that if a laboratory changes to a different assay kit, serial assays may yield nonequivalent PSA values.[8] A multicenter trial sponsored by the National Cancer Institute is underway to test the value of early detection on reducing mortality.[9]

Survival of the patient with prostatic carcinoma is related to the extent of the tumor. When the cancer is confined to the prostate gland, median survival in excess of 5 years can be anticipated. Patients with locally advanced cancer are not usually curable, and a substantial fraction will eventually die of their tumor, although median survival may be as long as 5 years. If prostate cancer has spread to distant organs, current therapy will not cure it. Median survival is usually 1 to 3 years, and the majority of such patients will die of prostate cancer. Even in this group of patients, however, indolent clinical courses lasting for many years may be observed.

Other factors affecting the prognosis of patients with prostate cancer that may be useful in making therapeutic decisions include histologic grade of the tumor, patient's age, other medical illnesses, and level of PSA.[10-14] Poorly differentiated tumors are more likely to have already metastasized by the time of diagnosis and are associated with a poorer prognosis. For patients treated with radiation therapy, the combination of clinical tumor (T) stage, Gleason score, and pretreatment PSA level can be used to more accurately estimate the risk of relapse.[15][Level of evidence: 3iDi] In the majority of studies, flow cytometry has shown that nuclear DNA ploidy is an independent prognostic indicator for progression and for cause-specific survival in patients with pathologic stages C and D1. Diploid tumors have a more favorable outcome than either tetraploid or aneuploid tumors. The use of flow cytometry techniques, histogram analysis, and computer-assisted cell morphology as tools to determine prognosis will require standardization.[16-20]

Definitive treatment is usually considered for younger men with prostate cancer and no major comorbid medical illnesses since they are more likely to die of prostate cancer than older men or men with major comorbid medical illness. Elevations of serum acid phosphatase are associated with poor prognosis in both localized and disseminated disease. PSA, an organ-specific marker with greater sensitivity and high specificity for prostate tissue, is often used as a tumor marker.[12,13,21-26] After radical prostatectomy, detectable PSA levels identify patients at elevated risk of local treatment failure or metastatic disease.[23] However, a significant proportion of patients with elevated or rising PSA levels after surgery may remain clinically free of symptoms for extended periods of time.[27] Therefore, biochemical evidence of failure on the basis of elevated or slowly rising PSA alone may not be sufficient to alter treatment. For example, in a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and who were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of greater than or equal to 0.2 ng/ml, felt to be evidence of "biochemical recurrence." Of these 315 men, 103 men (34%) developed clinical evidence of recurrence. The median time to development of clinical metastasis after biochemical recurrence was 8 years. Once the men developed metastatic disease, the median time to death was an additional 5 years.[28][Level of evidence: 3iiiA,B,D]

After radiation therapy with curative intent, persistently elevated or rising PSA may be a prognostic factor for clinical disease recurrence. However, reported case series have used a variety of definitions of "PSA failure." No definition has been shown to be an accurate surrogate for either clinical progression or survival.[29] Therefore, it is difficult to base decisions about instituting additional therapy on biochemical failure. The implication of the various definitions of "PSA failure" for overall survival is not known, and as in the surgical series, many biochemical relapses (rising PSA alone) may not be clinically manifested in patients treated with radiation.[30]

After hormonal therapy, reduction of PSA to undetectable levels provides information regarding the duration of progression-free status.[12] However, decreases in PSA of less than 80% may not be very predictive.[12] Yet, because PSA expression itself is under hormonal control, androgen deprivation therapy can decrease the serum level of PSA independent of tumor response. Therefore, clinicians cannot rely solely on the serum PSA level to monitor a patient's response to hormone therapy; they must also follow clinical criteria.[31]

References:

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2. Helgesen F, Holmberg L, Johansson JE, et al.: Trends in prostate cancer survival in Sweden, 1960 through 1988: evidence of increasing diagnosis of nonlethal tumors. Journal of the National Cancer Institute 88(17): 1216-1221, 1996.
3. Krahn MD, Mahoney JE, Eckman MH, et al.: Screening for prostate cancer: a decision analytic view. Journal of the American Medical Association 272(10): 773-780, 1994.
4. Kramer BS, Brown ML, Prorok PC, et al.: Prostate cancer screening: what we know and what we need to know. Annals of Internal Medicine 119(9): 914-923, 1993.
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23. Stamey TA, Kabalin JN: Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. I. Untreated patients. Journal of Urology 141(5): 1070-1075, 1989.
24. Stamey TA, Kabalin JN, McNeal JE, et al.: Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients. Journal of Urology 141(5): 1076-1083, 1989.
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