Digital rectal examination (DRE), serum prostate-specific antigen (PSA) testing, transrectal ultrasonography (TRUS) and biopsy are all modalities used in prostate cancer diagnosis. Of these, only biopsy can definitively establish the presence of malignant disease. 1
DRE
A DRE is the simplest means of detecting prostate cancer, although its accuracy is user-dependent.2,3 Abnormal findings on DRE include asymmetry of the gland, nodules, induration, lack of mobility and palpable seminal vesicles.2 Although a variety of other conditions can lead to DRE abnormalities (e.g. benign prostatic hyperplasia, prostatitis), suspicious findings are an absolute indication for biopsy,1 which will prove positive in around a third of cases.2
PSA testing
PSA is a glycoprotein secreted by the prostate that functions to liquefy semen.2 Under normal conditions, little PSA escapes from prostate tissue into the bloodstream, but PSA levels may become elevated in the presence of prostate cancer or non-malignant prostate conditions such as benign prostatic hyperplasia or inflammation4. Therefore, there is no widely accepted threshold above which a measurement can be considered abnormal.1 Although cut-offs of 3–4ng/ml have been applied in clinical studies,5 only 30% of men with PSA 4–10ng/ml will have prostate cancer and, conversely, around 15% with PSA beneath this range will harbour a malignancy6. Various methods have been proposed to improve the performance of PSA as a disease marker, including age-specific reference ranges, PSA density (PSA concentration divided by prostate volume), PSA subtypes (e.g. free PSA) and consideration of change in PSA levels over time (PSA kinetics) but seem to have limited usefulness in routine clinical settings so far.1
Recently, new tests have been developed to improve the sensitivity and specificity of prostate cancer detection. These include the prostate cancer gene-3 (PCA3) test, a molecular assay performed on urine obtained following a DRE7, and PSA phi, a parameter calculated from the concentration of the PSA precursor [-2]proPSA, which could have additional value with respect to prostate cancer detection is within PSA range 2-10ng/ml.8 Neither test is widely accepted or practiced as their role is still to be determined.
TRUS
Cancerous prostate glands can show a number of ultrasonographic abnormalities and classically appear hyperechoic.1,2 However, this pattern is not always observed and hypoechoic images may have other causes. Therefore the main roles of TRUS are to measure the size of the prostate gland and to guide the acquisition of biopsy samples, rather than as an isolated diagnostic modality.2
Biopsy
PSA elevations or suspicious findings on a DRE may indicate the need for a prostate biopsy.3 However, the decision to undergo a biopsy should be taken carefully and include consideration of other factors such as the patient’s age, potential comorbidities and risk factors.1,6 A single elevated PSA reading usually does not trigger an immediate biopsy.1
Diagnosis of prostate cancer is most often based on histopathological examination of core biopsy specimens, although surgical samples can also be used.6 Usually, TRUS is used to guide the sampling device to the appropriate area, where several samples are obtained (a minimum of eight is recommended) using an automated biopsy gun.1,2 The procedure is generally performed under local anaesthesia on an outpatient basis, with periprocedural antibiotic use to reduce the risk of infection.2 Although serious complications are rare, the procedure can be painful and around half of patients experience rectal haemorrhage, sometimes with urethral bleeding, which can be disturbing for patients.1,9
The diagnosis of prostate cancer is confirmed by the presence of adenocarcinoma on histological examination of biopsy tissue.1 In addition, prognostic information is gained from the Gleason score (see section on tumour grading),1 along with tumour volume measures (such as number of positive biopsy cores and extent of cancer in the affected cores).3 Patient information on this topic can be found at Unitedagainstprostatecancer.com.
References:
1. European Association of Urology. Guidelines on prostate cancer, 2010.
2. Kirby RS, Patel MI. Fast facts: prostate cancer (5th ed). Health Press Ltd: Oxford, 2008.
3. Wilt TJ, Thompson IM. Clinically localised prostate cancer. BMJ 2006;333:1102-6.
4. American Urological Association. Prostate-specific antigen best practice statement: 2009 update.
5. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-8.
6. National Institute for Health and Clinical Excellence. Clinical guideline 58. Prostate cancer, February 2008.
7. Schilling D, de Reijke T, Tombal B, et al. The Prostate Cancer gene 3 assay: indications for use in clinical practice. BJU Int 2010;105:452-5.
8. Jansen FH, van Schaik RH, Kurstjens J, et al. Prostate-Specific Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection. Europ Urology 2010;57:921-27.
9. Mäkinen T, Auvinen A, Hakama M, et al. Acceptability and complications of prostate biopsy in population-based PSA screening versus routine clinical practice: a prospective, controlled study. Urology 2002;60:846-50.