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Prostate Cancer: Diagnosis and Management in the Outpatient Clinic

David Thurtle

Prostate cancer is the commonest male solid organ malignancy. Approximately 50 000 men are diagnosed every year in the UK. Its prevalence and the high profile of the disease, means it represents a fair proportion of the workload for most practising adult urologists.

Most patients will first be referred with a raised prostate specific antigen (PSA) test. This simple and cheap blood test can lead to a multitude of investigations and treatments with significant potential morbidity, so it is important to be able to counsel men thoroughly. Unlike many cancers, some forms of non‐metastatic prostate cancer can very reasonably be monitored by ‘active surveillance’ (AS) rather than requiring universal treatment – creating decision dilemmas for patients and clinicians and emphasising the importance of understanding the disease thoroughly.

Pathology

The vast majority of prostate cancer is adenocarcinoma – from the glandular structures in the epithelial tissue. Very rarely, the prostate can be a site for sarcomas or secondary metastases. Most prostate adenocarcinomas occur in the peripheral zone (~75%), whereas the transitional zone is more commonly affected by benign enlargement. Prostate cancer is usually considered to be a multifocal disease.

Two histological lesions have traditionally been considered to be pre‐ or peri‐malignant lesions, namely, prostatic intraepithelial neoplasia (PIN) and atypical small acinar proliferation (ASAP). Only high‐grade PIN (HGPIN) should be recorded by pathologists. Isolated HGPIN or ASAP may lead to repeated biopsies, or longer PSA monitoring, but does not in itself require treatment.

Tumour Grading

Prostate cancer is graded using the Gleason score (GS), composed of two scores ranging from 1 to 5 based upon the morphology of the dominant and the non‐dominant cell pattern. Gleason score of 3 + 3 and above are considered to be cancer. In 2014 the International Society of Urological Pathologists published a revised cancer ‘Grade Group’ system which seeks to make the grading more intuitive – with grade groups 1 (GS 3 + 3), 2 (GS 3 + 4), 3 (GS 4 + 3), 4 (GS 8), and 5 (GS 9–10) ranging from the lowest to highest‐risk disease.

Biopsy characteristics have prognostic significance, as a surrogate for disease volume and multifocality. Proportion of biopsy cores involved, maximum tumour length, and total biopsy percentage are sometimes used.

History

History‐taking for a man suspected to have prostate cancer can be considered in two parts – risk factors for the disease and symptoms of the disease:

Risk Factors

Age – Prostate cancer prevalence increases with age. Incidence rates are highest in men aged between 75 and 79. The disease is very rare under the age of 40, whereas cadaveric studies have shown the prevalence to be in excess of 50% by age 80 – though much of this will not be indolent.

Hormones – Benign or malignant growth of the prostate is under the influence of testosterone and it’s active metabolite dihydrotestosterone (DHT). Therefore, men who take additional testosterone may be at higher risk of the disease. Men on testosterone replacement therapy, tend to have their PSA monitored for this reason. Conversely, 5‐alpha reductase inhibitors (5‐ARI) (e.g., finasteride) have the effect of shrinking the prostate reducing PSA values. PSA values among men on 5‐ARIs are usually doubled to compensate for this effect. Impact of long term 5‐ARIs on prostate cancer is debated.

Race – The disease is more common and aggressive among black men than Caucasians. Men of Asian or Oriental origin tend to be at lower risk.

Family history – Carriers of the breast cancer susceptibility protein (BRCA) gene mutations are at increased risk, and may have more aggressive, prostate cancer. Family history should therefore enquire about breast and ovarian malignancies among relatives, as well as prostate cancer. Men with one first degree relative affected by prostate cancer are approximately twice as likely to develop prostate cancer, with the risk increasing with more affected relatives.

Obesity – Emerging research suggests obese men are at higher risk of prostate cancer, and have worse outcomes from the disease, with the effect thought to be multifactorial.

Diet and lifestyle – Prostate cancer is not thought to have a direct association with smoking. Some foods, such as lycopenes (e.g., tomatoes) and cruciferous vegetables (e.g., broccoli) are thought to have protective effects against prostate cancer.

Symptoms of the Disease

As prostate cancer tends to affect the peripheral zone of the prostate, it is often completely asymptomatic.

Lower urinary tract symptoms (LUTS) such as nocturia, frequency, hesitancy, urgency, or retention are more likely to be a result of benign prostatic enlargement, but can suggest underlying malignancy. Regardless, existing LUTS may have an impact on eventual treatment decisions. Primary care guidelines often suggest considering a PSA test in men with LUTS, as well as those with erectile dysfunction.

Haematuria and haematospermia, have been associated with prostate cancer, although more common causes for both exist. Isolated haematospermia is generally benign and self‐limiting.

Symptoms of advanced disease may be more systemic, such as weight loss and lethargy. Localised extension can lead to perineal pain, renal failure and anuria and rarely even malignant priapism or rectal obstruction. Symptoms of bone metastases such as back pain, bone pain, anaemia, and neurological symptoms in the lower limbs suggest advanced disease.

Sex and fertility are important considerations, and erectile function should be documented, as potential treatments may affect these.

Examination and Investigation

In addition to a history, examination, and PSA, most new patients with PSA < ~30 are best investigated with upfront pre‐biopsy multi‐parametric magnetic resonance imaging (mpMRI) (see below). If subsequent biopsy demonstrates low‐risk disease, further staging investigations can be omitted. For high‐risk cases, bone scan and computed tomography (CT) are used for staging. A patient presenting with symptoms or high PSA (>50) suggestive of advanced disease could proceed directly to bone scan without need for an mpMRI.

Digital rectal examination (DRE) of the prostate is a quick and simple test that should not be omitted, although it is widely appreciated that correlation between DRE and MRI or pathological findings is poor. DRE can be useful to detect obviously malignant prostates, which tend to feel hard, fixed, craggy, nodular, and asymmetric. DRE can also help roughly quantify prostate volume to contextualise the PSA value, and to identify competing diagnoses such as a tender boggy prostate suggesting prostatitis.

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