Causes of Elevation

There are several major causes of increased serum PSA, including BPH, prostate cancer, prostate inflammation or infection, and prostate or perineal trauma. Although the PSA per gram of tissue is higher in malignant compared with benign prostate tissue, BPH is still the most common cause of elevated serum PSA. In addition to producing more PSA per gram of tissue, invasive prostate cancer can disrupt the prostate-blood barrier, further increasing serum PSA. In men with prior negative prostate biopsies, prostate acute and chronic inflammation is found to be more prevalent in patients with elevated serum PSA levels (> 4 ng/mL) compared with those with lower levels. Furthermore, although some have reported that free to total PSA ratios are not affected by the presence of inflammation, others have shown that these ratios are unable to distinguish chronic prostatitis from prostate cancer, as both may significantly decrease the ratio, raising the suspicion of prostate cancer.

From a practical standpoint, prostate instrumentation or "trauma" from cystoscopy, prostate biopsy, transurethral resection (TURP), vigorous digital rectal examination (DRE), or ejaculation may cause transient increases in serum PSA. In one study, men undergoing biopsy experienced a median 7.9 ng/mL increase and those undergoing TURP experienced a median of 5.9 ng/mL elevation. The median time for PSA to return to baseline following biopsy was 15-17 days and following TURP was 18 days. The changes in PSA following rigid and flexible cystoscopy were less pronounced at 0.1 and 0.5 ng/mL, respectively. Although DRE has been shown to cause transient and minimal increases in PSA, the PSA changes have been reported to have little clinical significance. Likewise, ejaculation can minimally elevate the serum PSA for approximately 48-72 hours. Taken as a whole, serum PSA levels after cystoscopy and DRE are believed to be accurate and reliable, a serum PSA level should not be obtained 48-72 hours post ejaculation, and a period of at least 4-6 weeks should elapse after a biopsy or TURP before PSA levels are measured.

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