200 CHAPTER 6 Urological neoplasia

PSA derivatives: free-to-total ratio, density, and velocity

Measurement of the free-to-total (F:T) PSA ratio can increase the specificity of total PSA because the ratio is lower in men with prostate cancer than in men with benign hyperplasia. Most urologists use this in deciding whether to rebiopsy a patient with previous benign biopsies, instead of using this to decide about the need for a first-time biopsy.

As an example, a man with a normal DRE and a PSA of 4–10 ng/mL has a 27% risk of prostate cancer. This risk rises to 60% if the F:T ratio is 10% and falls to 10% if his ratio is >25%. The F:T ratio is most useful in the total PSA range 2.5–10 ng/mL.

Consideration may be given to the prostate volume, since large benign prostates are the most common cause of mildly elevated PSA. Serum PSA/ prostate volume = PSA density, and serum PSA/prostate transition-zone volume = PSA-TZ density. Various cutoff densities have been proposed to raise the specificity of total PSA, possibly to reduce the need for prostatic biopsy, but the issue remains controversial.

Short-term variations in serum PSA occur in the presence or absence of cancer, the cause of which may be technical or physiological. Longer term, the PSA tends to rise slowly due to BPH and faster due to prostate cancer—PSA velocity.

A PSA velocity >0.75 ng/mL per year with at least three determinations over at least 18 months is suggestive of the presence of PC. Recent studies have lowered this threshold significantly and some authorities believe it should no longer be considered as an indication for biopsy. A high pretreatment PSA velocity (>2.0 ng/mL/year) has been shown to correlate with a worse prognosis after radiotherapy or radical surgery.

PSA doubling time (PSADT) is the time it takes for a PSA value to double, based on an exponential growth pattern. Pretreatment PSADT has little diagnostic value. PSADT is an important predictor of tumor progression, therapeutic outcome, and tumor-specific mortality. Following surgery or radiotherapy for prostate cancer, PSADT <6 months indicates distant disease progression, whereas a more delayed PSADT suggests local recurrence.

Other markers are being studied for the diagnosis of prostate cancer. Urine-based analysis of PCA3 is promising. The biomarker known as early prostate cancer antigen-2 (EPCA-2) is also showing promise in identifying which patients with an elevated PSA may have cancer.

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202 CHAPTER 6 Urological neoplasia

Prostate cancer: transrectal ultrasonography and biopsies

The most common diagnostic modality for prostate cancer is currently transrectal ultrasonography (TRUS) with guided biopsies (Fig. 6.1). TRUS provides imaging of the prostate and seminal vesicles using a 7.5 mHz biplane intrarectal probe measuring approximately 1.5 cm in diameter.

While TRUS imaging may be performed for other reasons (e.g., evaluation of infertility, sizing for treatment planning), a TRUS without biopsy is considered an inadequate way to evaluate for prostate cancer. Many advocate use of an enema before the biopsy to enhance visualization.

The ultrasound-guided periprostatic injection of local anesthetic (1% lidocaine) has become the standard in the United States when biopsy is planned. Rarely, general or regional anesthesia may be necessary, especially in the presence of anal stenosis or if saturation (>20) biopsies are planned.

A careful DRE precedes insertion of the probe. Broad-spectrum antimicrobials (e.g., quinolone antibiotic) are given before and after the procedure.

TRUS can image the outline of the prostate, cysts, abscesses, and calcifications within the prostate. Hypoechoic and hyperechoic lesions in the peripheral zone may be due to prostate cancer or inflammatory conditions, although most prostate cancers are in fact isoechoic and are not visualized on ultrasound.

Advanced biopsy techniques that use microbubble contrast agents with and without color Doppler are being actively investigated to improve yield. There are no convincing data that color Doppler alone can improve the yield of prostate biopsy over the standard grayscale biopsy.

Indications for TRUS without biopsy

•Accurate measurement of prostate volume for treatment planning (e.g., microwave, needle ablation, brachytherapy)

•Male infertility with azoospermia, to look for seminal vesicle and ejaculatory duct obstruction due to calculus or Müllerian cyst

•Suspected prostatic abscess (can be drained by needle aspiration)

•Investigation of chronic pelvic pain, looking for prostatic cyst or calculi

Indications for TRUS with biopsies

•An abnormal DRE and/or an elevated PSA (exceptions include very elderly men with massively elevated PSA and abnormal DRE, or those in whom a TURP is indicated for severe LUTS/retention where histology will be obtained). See Table 6.1 (p. 199).

•Previous biopsies showing multifocal high-grade PIN or ASAP

•Previous biopsies normal, but PSA rising or DRE abnormal

•To confirm viable prostate cancer following treatment if further treatment is being considered

PROSTATE CANCER: TRANSRECTAL ULTRASONOGRAPHY & BIOPSIES 203

Figure 6.1 Transrectal ultrasound scanning (TRUS). An ultrasound probe is inserted into the rectum to guide the biopsy needle into the correct position so that multiple core biopsies can be taken from different areas of the prostate.

Biopsy protocol

Ten to 12 18 French Tru-Cut needle biopsies are taken in a systematic fashion to include any palpable or sonographic target lesion. The traditional sextant protocol (a parasagittal base, mid-gland, and apex from each side) is no longer considered an adequate technique. To the 10–12 biopsy regimen, add samples from the far lateral peripheral zones (Fig. 6.2). Studies have demonstrated that these extra biopsies detect up to 15% more cancers.

Additional biopsies of each transition zone may be taken if a transition zone cancer is suspected or if a patient is undergoing repeat biopsies due to a rising PSA. Seminal vesicles biopsies occasionally add staging information if they appear abnormal on DRE, TRUS, or MRI.

Complications of prostatic biopsy

•Occasional vasovagal reaction (fainting) immediately after procedure

•Small risk of urinary tract infection and rarely urosepsis, which may be life threatening

•Small risk of significant rectal bleeding

•Mild hemospermia or hematuria, for several weeks after the procedure

Prostate cancer may also be diagnosed by transurethral resection of the prostate (TURP) histology or clinically (without histology) in certain circumstances. For example, it could be viewed as unnecessarily invasive to biopsy an elderly and frail symptomatic patient with a rock-hard prostate and a PSA of >100 ng/mL prior to commencing hormone therapy.

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