General Information About Prostate Cancer–Health Professional Version
The median age at diagnosis of prostate cancer is 67 years. Prostate cancer may be cured when localized, and it frequently responds to treatment when widespread. 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 bone. The 5-year relative survival rate for men diagnosed in the United States from 2013 to 2019 with local or regional disease was greater than 99%, and the rate for distant disease was 34%; a 97% survival rate was observed for all stages combined. 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.
Many patients—especially those with localized tumors—may die of other illnesses without ever having suffered disability from prostate cancer, even if managed conservatively without an attempt at curative therapy. In part, these favorable outcomes are likely the result of widespread screening with the prostate-specific antigen (PSA) test, which can identify patients with asymptomatic tumors that have little or no lethal potential. There is a large number of these clinically indolent tumors, estimated to range from 30% to 70% of men older than 60 years, based on autopsy series of men dying of causes unrelated to prostate cancer.
Because diagnostic methods have changed over time, any analysis of survival after treatment of prostate cancer and comparison of the various treatment strategies is complicated by evidence of increasing diagnosis of nonlethal tumors. Nonrandomized comparisons of treatments may be confounded not only by patient selection factors but also by time trends.
For example, a population-based study in Sweden showed that, from 1960 to the late 1980s, before the use of 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 use of watchful waiting or active surveillance or palliative hormonal treatment as the most common treatment strategies for localized prostate cancer during the entire era (150 radical prostatectomies per year were performed in Sweden during the late 1980s). The investigators estimated that, if all prostate cancers diagnosed between 1960 and 1964 were of the lethal variety, then at least 33% of cancers diagnosed between 1980 and 1984 were of the nonlethal variety. With the advent of PSA screening as the most common method of detection in the United States, the ability to diagnose nonlethal prostate cancers has further increased.
Another issue complicating comparisons of outcomes among nonconcurrent series of patients is the possibility of changes in criteria for the histological diagnosis of prostate cancer. This phenomenon creates a statistical artifact that can produce a false sense of therapeutic accomplishment and may also lead to more aggressive therapy.
Controversy exists about the value of screening, the most appropriate staging evaluation, and the optimal treatment of each stage of the disease.
Incidence and Mortality
Estimated new cases and deaths from prostate cancer in the United States in 2024:
- New cases: 299,010.
- Deaths: 35,250.
Anatomy
Screening
Screening for prostate cancer is controversial. In the United States, most prostate cancers are diagnosed because of screening, either with a PSA blood test or, less frequently, with a digital rectal examination. Randomized trials have yielded conflicting results. Systematic literature reviews and meta-analyses have reported no clear evidence that screening for prostate cancer decreases the risk of death from prostate cancer, or that the benefits outweigh the harms of screening.
For a detailed summary of evidence regarding the benefits and harms of screening for prostate cancer, see Prostate Cancer Screening.
Pathology
More than 95% of primary prostate cancers are adenocarcinomas. Prostate adenocarcinomas are frequently multifocal and heterogeneous in patterns of differentiation. Prostatic intraepithelial neoplasia (PIN) (noninvasive atypical epithelial cells within benign-appearing acini) is often present in association with prostatic adenocarcinoma. PIN is subdivided into low grade and high grade. The high-grade form may be a precursor of adenocarcinoma.
Several rare tumors account for the rest of the cases. These include the following:
- Small-cell tumors.
- Intralobular acinar carcinomas.
- Ductal carcinomas.
- Clear cell carcinomas.
- Mucinous carcinomas.
Gleason score
The histological grade of prostate adenocarcinomas is usually reported according to one of the variations of the Gleason scoring system, which provides a useful, albeit crude, adjunct to tumor staging in determining prognosis. The Gleason score is calculated based on the dominant histological grades, from grade 1 (well differentiated) to grade 5 (very poorly differentiated). The classical score is derived by adding the two most prevalent pattern grades, yielding a score ranging from 2 to 10. Because there is some evidence that the least-differentiated component of the specimen may provide independent prognostic information, the score is often provided by its separate components (e.g., Gleason score 3 + 4 = 7; or 4 + 3 = 7).
There is evidence that, over time, pathologists have tended to award higher Gleason scores to the same histological patterns, a phenomenon sometimes termed grade inflation. This phenomenon complicates comparisons of outcomes in current versus historical patient series. For example, prostate biopsies from a population-based cohort of 1,858 men diagnosed with prostate cancer from 1990 through 1992 were re-read in 2002 to 2004. The contemporary Gleason score readings were an average of 0.85 points higher (95% confidence interval, 0.79–0.91; P .001) than the same slides read a decade earlier. As a result, Gleason-score standardized prostate cancer mortality rates for these men were artifactually improved from 2.08 to 1.50 deaths per 100-person years—a 28% decrease even though overall outcomes were unchanged.
Molecular markers
A number of tumor markers are associated with the outcome of patients with prostate cancer, including the following:
- Markers of apoptosis including Bcl-2, Bax.
- Markers of proliferation rate, such as Ki67.
- TP53 mutation or expression.
- p27.
- E-cadherin.
- Microvessel density.
- DNA ploidy.
- p16.
- PTEN gene hypermethylation and allelic losses.
However, none of these has been prospectively validated, and they are not a part of the routine management of patients.
Clinical Presentation
In the United States, most prostate cancers are diagnosed as a result of screening; therefore, symptoms of cancer are infrequent at the time of diagnosis. Nevertheless, local growth of the tumor may produce symptoms of urinary obstruction such as:
- Decreased urinary stream.
- Urgency.
- Hesitancy.
- Nocturia.
- Incomplete bladder emptying.
These symptoms are nonspecific and more indicative of benign prostatic hyperplasia than cancer.
Although rare in the current era of widespread screening, prostate cancer may also present with symptoms of metastases, including bone pain, pathological fractures, or symptoms caused by bone marrow involvement.
Diagnostic Evaluation
Needle biopsy is the most common method used to diagnose prostate cancer. Most urologists now perform a transrectal biopsy using a bioptic gun with ultrasound guidance. Less frequently, a transperineal ultrasound-guided approach can be used in patients who may be at increased risk of complications from a transrectal approach. Over the years, there has been a trend toward taking eight to ten or more biopsy samples from several areas of the prostate with a consequent increased yield of cancer detection after an elevated PSA blood test.
The use of magnetic resonance imaging (MRI)−directed biopsy in the initial diagnostic evaluation of prostate cancer is also being studied, either as a replacement for, or in addition to, standard systematic prostate needle biopsies. The data have been reported primarily by experienced MRI radiologists and urologists in referral centers, and generalizability of results is uncertain. A multicenter randomized trial of 500 patients has shown that, in experienced hands, a multiparametric MRI-directed biopsy is more accurate than a transrectal-guided biopsy to detect clinically significant cancers. MRI led to the detection of more Gleason score (≥7) lesions and fewer Gleason score (7) lesions, with fewer biopsies overall. The data suggested that MRI-directed biopsy can replace standard transrectal-guided biopsies. However, a large, single-arm, single-center study of 2,103 men with MRI-visible lesions who underwent both MRI-directed biopsies and standard systematic prostate needle biopsies under ultrasound visualization suggested otherwise. In that study, MRI-directed biopsies alone led to misclassification of 8.8% of cancers defined as clinically significant (Gleason score 4 + 3 or higher) compared with the combination of both biopsy techniques. Both studies reported only on histology end points at the time of diagnosis, rather than health outcomes on follow-up.
Prophylactic antibiotics, especially fluoroquinolones, are often used before transrectal needle biopsies. There are reports of increasing rates of sepsis, particularly with fluoroquinolone-resistant E. coli, and hospitalization after the procedure. Therefore, men undergoing transrectal biopsy should be told to seek medical attention immediately if they experience fever after biopsy.
Prognostic Factors
The following factors influence the survival of patients with prostate cancer:
- Extent of tumor.
- Histological grade of tumor.
- Patient's age and health.
- Prostate-specific antigen (PSA) level.
For more information on survival rates, see Cancer Stat Facts: Prostate Cancer.
Extent of tumor
When the cancer is confined to the prostate gland, long-term prognosis is excellent. Patients with locally advanced cancer are not usually curable, but 5-year survival is still very good. If prostate cancer has spread to distant organs, current therapy will not cure it. Median survival is usually 1 to 3 years, and most of these patients will die of prostate cancer. Even in this group of patients, indolent clinical courses lasting for many years may be observed.
Histological grade of tumor
Poorly differentiated tumors are more likely to have metastasized before diagnosis and are associated with a poorer prognosis. The most commonly used method to report tumor differentiation is the Gleason score. For more information, see the Pathology section.
Patient's age and health
Any benefits of definitive local therapy with curative intent may take years to emerge. Therefore, therapy with curative intent is usually reserved for men with a sufficiently long life expectancy. For example, radical prostatectomy is often reserved for men with an estimated life expectancy of at least 10 years.
Prostate-specific antigen (PSA) level
PSA, an organ-specific marker, is often used as a tumor marker. The higher the level of PSA at baseline, the higher the risk of metastatic disease or subsequent disease progression. However, it is an imprecise marker of risk.
For example, baseline PSA and rate of PSA change were associated with subsequent metastasis or prostate cancer death in a cohort of 267 men with clinically localized prostate cancer who were managed by watchful waiting or active surveillance in the control arm of a randomized trial comparing radical prostatectomy with watchful waiting or active surveillance. Nevertheless, the accuracy of classifying men into groups whose cancer remained indolent versus those whose cancer progressed was poor at all examined cut points of PSA or PSA rate of change.
Serum acid phosphatase levels
Elevations of serum acid phosphatase are associated with poor prognosis in both localized and disseminated disease. However, serum acid phosphatase levels are not incorporated into the American Joint Committee on Cancer's (AJCC) staging system for prostate cancer.
Use of nomograms as a prognostic tool
Several nomograms have been developed to predict outcomes either before radical prostatectomy or after radical prostatectomy with intent to cure. Preoperative nomograms are based on clinical stage, PSA level, Gleason score, and the number of positive and negative prostate biopsy cores. One independently validated nomogram demonstrated increased accuracy in predicting biochemical recurrence-free survival by including preoperative plasma levels of transforming growth factor B1 and interleukin-6 soluble receptor.
Postoperative nomograms add pathological findings, such as capsular invasion, surgical margins, seminal vesicle invasion, and lymph node involvement. The nomograms, however, were developed at academic centers and may not be as accurate when generalized to nonacademic hospitals, where most patients are treated. In addition, the nomograms use nonhealth (intermediate) outcomes, such as PSA rise or pathological surgical findings, and subjective end points, such as the physician's perceived need for additional therapy. In addition, the nomograms may be affected by changing methods of diagnosis or neoadjuvant therapy.
Follow-Up After Treatment
The optimal follow-up strategy for men treated for prostate cancer is uncertain. Men should be interviewed and examined for symptoms or signs of recurrent or progressing disease, as well as side effects of therapy that can be managed by changes in therapy. However, using surrogate end points for clinical decision-making is controversial, and the evidence that changing therapy based on such end points translates into clinical benefit is weak. Often, rates of PSA change are thought to be markers of tumor progression. However, even though a tumor marker or characteristic may be consistently associated with a high risk of prostate cancer progression or death, it may be a very poor predictor and of very limited utility in making therapeutic decisions.
Although the PSA test is nearly universally used to follow patients, the diversity of recommendations on the provision of follow-up care reflects the current lack of research evidence on which to base firm conclusions. A systematic review of international guidelines highlights the need for robust primary research to inform future evidence-based models of follow-up care for men with prostate cancer.
Preliminary data from a retrospective cohort of 8,669 patients with clinically localized prostate cancer treated with either radical prostatectomy or radiation therapy suggested that short posttreatment PSA doubling time (3 months in this study) fulfills some criteria as a surrogate end point for all-cause mortality and prostate cancer-specific mortality after surgery or radiation therapy.
Likewise, a retrospective analysis (SWOG-S9916 ) showed PSA declines of 20% to 40% (but not 50%) at 3 months and 30% or more at 2 months after initiation of chemotherapy for hormone-independent prostate cancer, and fulfilled several criteria of surrogacy for overall survival (OS).
These observations should be independently confirmed in prospective study designs and may not apply to patients treated with hormonal therapy. In addition, there are no standardized criteria of surrogacy or standardized cut points for adequacy of surrogate end points, even in prospective trials.
Follow-up after radical prostatectomy
After radical prostatectomy, a detectable PSA level identifies patients at elevated risk of local treatment failure or metastatic disease; however, a substantial proportion of patients with an elevated or rising PSA level after surgery remain clinically free of symptoms for extended periods. Biochemical evidence of failure on the basis of elevated or slowly rising PSA alone, therefore, may not be sufficient to initiate additional treatment.
For example, in a retrospective analysis of nearly 2,000 men who had undergone radical prostatectomy with curative intent and were followed for a mean of 5.3 years, 315 men (15%) demonstrated an abnormal PSA of 0.2 ng/mL or higher, which is considered evidence of biochemical recurrence. Among these 315 men, 103 (34%) developed clinical evidence of recurrence. The median time to the development of clinical metastasis after biochemical recurrence was 8 years. After the men developed metastatic disease, the median time to death was an additional 5 years.
Follow-up after radiation therapy
For patients treated with radiation therapy, the combination of clinical tumor stage, Gleason score, and pretreatment PSA level is often used to estimate the risk of relapse. As is the case after prostatectomy, PSA is often followed for signs of tumor recurrence after radiation therapy. 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. Criteria have been developed by the American Society for Therapeutic Radiology and Oncology Consensus Panel. It is difficult to base decisions about initiating additional therapy on biochemical failure alone. The implication of the various definitions of PSA failure for OS is not known, and, as in the surgical series, many biochemical relapses (rising PSA only) may not be clinically manifested in patients treated with radiation therapy.
Follow-up after hormonal therapy
After hormonal therapy, reduction of PSA to undetectable levels provides information regarding the duration of progression-free status; however, decreases in PSA of less than 80% may not be very predictive. Because PSA expression itself is under hormonal control, androgen deprivation therapy can decrease the serum level of PSA independent of tumor response. Clinicians, therefore, cannot rely solely on the serum PSA level to monitor a patient’s response to hormonal therapy; they must also follow clinical criteria.
Source: PDQ® Adult Treatment Editorial Board. PDQ Prostate Cancer Treatment. Bethesda, MD: National Cancer Institute.