Evidence of Benefit
Frequency of screening
The optimal frequency and age range for PSA (and DRE) testing are unknown.[61,68,69] Cancer detection rates have been reported to be similar for intervals of 1 to 4 years. With serial annual screening in the PLCO trial, 8% of men with baseline PSA lower than 1 ng/mL had a prostate cancer diagnosis within 2 years. In the same trial, 2-year intervals in screening produced average delays of 5.4 to 6.5 months, while 4-year screening intervals produced average delays of 15.6 months (baseline PSA < 1 ng/mL) to 20.9 months (baseline PSA 3-4 ng/mL). While the authors caution that an optimal prostate screening frequency cannot be determined from these data, they conclude that among men who choose to be screened, these data may provide a context for determining a PSA screening schedule.
A report from the ERSPC trials demonstrated that while more frequent screenings lead to more diagnosed cancers, the detection rates for aggressive interval cancers was very similar with the different screening intervals in place in the two countries reporting (0.11 with a 4-year interval in Rotterdam and 0.12 with a 2-year interval in Gothenburg). The report suggests that mortality outcomes from the ERSPC (2- and 4-year intervals) and PLCO (1-year interval) trials should facilitate a more reliable assessment of the benefits and costs of different screening intervals.
Types of Tumors Detected by Prostate Cancer Screening
Of serious concern with regard to prostate cancer screening is the high background histologic prevalence of the disease. It has been demonstrated that a considerable fraction (approximately one-third) of men in their fourth and fifth decades have histologically evident prostate cancer. Most of these tumors are well-differentiated and microscopic in size. Conversely, evidence suggests that tumors of potential clinical importance are larger and of higher grade. Since the inception of PSA screening, several events have occurred: (1) a contemporaneous but unrelated decrease in detections of transition-zone tumors caused by a fall in the number of transurethral resections of the prostate due to the advent of effective treatment for benign prostatic hyperplasia (including alpha blockers and finasteride); and (2) an increase in detection of peripheral-zone tumors due to the incorporation of TRUS-guided prostate biopsies. Because transition-zone tumors are predominantly low volume and low grade and because peripheral-zone tumors have a preponderance of moderate-grade and high-grade disease, the proportion of higher grade tumors detected by current screening practices has increased substantially. A Detroit study found that between 1989 and 1996, poorly differentiated tumors remained stable and well-differentiated tumors fell in frequency while moderately differentiated disease increased in frequency. The largest rise in incidence was in clinically localized disease. It is now known that systematic changes to the histological interpretation of biopsy specimens by anatomical pathologists has occurred during the PSA screening era (i.e., since about 1985) in the United States. This phenomenon, sometimes called "grade inflation," is the apparent increase in the distribution of high-grade tumors in the population over time but in the absence of a true biological or clinical change. It is possibly the result of an increasing tendency for pathologists to read tumor grade as more aggressive.