There is evidence that, over time, pathologists have tended to award higher Gleason scores to the same histologic patterns, a phenomenon sometimes termed "grade inflation."[23,24] 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.[23,24] 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.
A number of tumor markers have been reported to be associated with the outcome of prostate cancer patients.[20,21] These include:
- Markers of apoptosis including Bcl-2, Bax.
- Markers of proliferation rate, such as Ki67.
- p53 mutation or expression.
- Microvessel density.
- DNA ploidy.
- 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.
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.
- 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, such as bone pain, pathologic fractures, or symptoms caused by bone marrow involvement.
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. 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. Less frequently, a transperineal, ultrasound-guided approach can be used in patients who may be at increased risk of complications caused by using a transrectal approach.