COUNSELING BEFORE PROSTATE CANCER SCREENING 195

Counseling before prostate cancer screening

Discussing the risks and benefits of prostate cancer screening is considered mandatory before offering a PSA and DRE to asymptomatic men. Such counseling is less controversial when evaluating a symptomatic patient, because a diagnosis of prostate cancer could alter the management. However, all patients should be informed when PSA testing is being considered.

The following points should be considered when counseling asymptomatic men:

•Cancer will be identified in up to 5% men screened.

•Screening enables earlier cancer detection and has the potential to decrease mortality rates.

•Early detection and treatment may avoid future cancer–related illness.

•DRE and PSA measurements can have both false-positive and falsenegative results.

•Prostatic biopsy can be uncomfortable and carries a small risk of sepsis or significant bleeding.

•Repeat biopsy may be recommended (PIN, ASAP, or rising PSA).

•Treatment may not be necessary, or may not be curative.

•Aggressive therapy is necessary to realize any benefit from screening if cancer is found based on the screening biopsy.

•Treatment-related morbidity could lead to a reduction in quality of life.

•Active surveillance may be recommended if a low-risk cancer is found.

196 CHAPTER 6 Urological neoplasia

Prostate cancer: clinical presentation

Since the widespread use of serum PSA testing, the majority of patients now have organ-confined disease at presentation. Shown below are the possible presentations, grouped by disease stage.

Localized prostate cancer (T1–2)

•Asymptomatic, detected through screening serum PSA (most common) or incidental digital rectal examination (DRE)

•Lower urinary tract symptoms (LUTS) (probably due to coexisting benign hyperplasia causing bladder outflow obstruction)

•Hematospermia

•Hematuria (probably due to coexisting benign hyperplasia)

•Perineal discomfort (probably due to coexisting prostatitis)

Locally advanced cancer (T3–4)

•Asymptomatic, with screening serum PSA or incidental DRE

•Lower urinary tract symptoms

•Hematospermia

•Hematuria

•Perineal discomfort

•Symptoms of renal failure/anuria due to ureteral obstruction

•Malignant priapism (rare)

•Rectal obstruction (rare)

Metastatic disease (N+, M+)

•Asymptomatic (“occult disease”), with screening serum PSA or incidental DRE

•Swelling of lower limb due to malignant lymphatic obstruction

•Anorexia, weight loss

•Bone pain, pathological fracture

•Neurological symptoms/signs in lower limbs (spinal cord compression)

•Anemia

PROSTATE CANCER: CLINICAL PRESENTATION 197

Box 6.1 A note about DRE

Since most prostate cancers arise in the peripheral, posterior part of the prostate, they may be palpable on DRE. An abnormal DRE is defined by asymmetry, a nodule, or a fixed, “rock hard” mass. Less than 50% of abnormal DREs are associated with prostate cancer, the remainder being benign hyperplasia, prostatic calculi, chronic prostatitis, or posttherapy changes (TURP, biopsy, radiation therapy).

Only 40% of cancers diagnosed by DRE will be organ confined. The fact that an abnormal DRE in the presence of a low PSA carries a 20–30% chance of predicting prostate cancer rules out any suggestion that the DRE could be abandoned as part of our screening approach.

The utility of the DRE in men on 5A-reductase inhibitors is maintained and in some cases may actually be enhanced through the volume effects of reduction in the overall size of the gland.

198 CHAPTER 6 Urological neoplasia

PSA and prostate cancer

See p. 39 for an introduction to the serum PSA test. Until the development of commercial serum PSA assays in the late 1980s, the only serum marker for prostate cancer was acid phosphatase. This was highly specific for prostate cancer metastatic to bone, but lacked sensitivity in detecting less advanced disease and was even normal in >20% patients with bone metastases.

PSA is a glycoprotein produced primarily by the prostatic acini and disruption of the prostatic architecture by disease states appears to allow more PSA to leak into the bloodstream.

Prior to the PSA era, most men with newly diagnosed prostate cancer had advanced and mostly incurable disease. PSA has revolutionized the diagnosis and management of prostate cancer, although its use in screening and early detection remains controversial.

The predictive values of PSA and DRE for diagnosing prostate cancer in biopsies are shown in Table 6.1. The Prostate Cancer Prevention Trial (PCPT) has forever changed our definition of what a “normal” PSA is. A surprising finding in this study was the high prevalence of prostate cancer among men without clinical suspicion for prostate cancer, including men with PSA levels fewer than 4 ng/mL.

AUA PSA Best Practice Policy 2009 no longer recommends a single, threshold value of PSA that should prompt prostate biopsy. The decision should be based primarily on PSA and DRE results, but should take into account multiple factors, including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history, and comorbidities. In addition to its use as a serum marker for the diagnosis of prostate cancer, PSA elevations may help in staging, counseling, and monitoring prostate cancer patients.

PSA derivatives (see p. 200) are also useful. Here are some examples:

PSA generally increases with advancing stage and tumor volume, although a small proportion of poorly differentiated tumors fail to express PSA. In men taking 5A-reductase inhibitors such as finasteride or dutasteride for benighn prostatic hyperplasia (BPH) or taking finasteride to treat alopecia, the production of PSA will be suppressed by about 50% at 6 months. Therefore, a corrected PSA should be twice the measured value when these drugs are used. This maintains the utility of PSA as a screening tool for prostate cancer detection.

PSA is used, along with clinical (DRE) T stage and Gleason score, to predict pathological tumor staging and outcome after radical treatments, using statistically derived nomograms and tables as noted on p. 208.

•>50% of patients have extraprostatic disease if PSA >10 ng/mL.

•<5% of patients have lymph node metastases and only 1% have bone metastases if PSA <20 ng/mL.

•66% of patients have lymphatic involvement and 90% have seminal vesicle involvement if PSA >50 ng/mL.

PSA AND PROSTATE CANCER 199

•PSA should be virtually undetectable following radical prostatectomy for gland-confined disease (usually < 0.2 ng/mL). A progressive rise in PSA (continuing to rise above 0.5 ng/mL) after radical prostatectomy precedes the development of clinical metastatic disease by a mean time of 8 years.

PSA falls to within the normal range in 80% of patients with metastatic disease on hormone therapy within 4 months; the PSA rises in a mean time of 18 months after starting hormone therapy, signaling progressive hormone refractory (castrate resistant) disease.

PSA is prostate specific, but unfortunately not prostate cancer specific. Other causes of elevated serum PSA include recent instrumentation (cystoscopy, catheterization for retention), prostate surgical intervention (biopsy, TRUP, laser or microwave ablation), urinary tract infection, including acute (NIH I) or chronic (NIH II) bacterial prostatitis.

In the presence of infection or instrumentation, PSA should not be measured until at least 28 days after the event, to avoid a false-positive result. Ideally, PSA should not be requested within 2 days of ejaculation, as a small number of men may have a transient rise. Routine DRE does not appear to cause any significant changes in PSA levels.

Table 6.1 Predictive value of PSA and DRE for biopsy diagnosis of prostate cancer