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Prostate cancer

Written by Esther Yuk Lim Yap

Last Reviewed: September 2019

Review Due: September 2020

 

DEFINITION

'malignant transformation of prostate gland cells, most commonly in the posterior part of the prostate. The tumour is always an adenocarcinoma'

 

AETIOLOGY

Age

 High incidence in male patients > 60 years old, rare in <50 years old

Ethnicity 

Increased risk in non-Caucasian men

Geography 

High incidence in North America and northwest Europe

Genetics 

1 first degree relative with prostate cancer 🡪 2 fold increased risk, mutations in DNA repair genes such as BRCA2 & BRCA1 🡪 increased risk of more aggressive disease. However, only 9% of cases are purely hereditary).

Diet rich in animal fats

SIGNS AND SYMPTOMS

At diagnosis, approximately 80% of patients have localised disease, small proportion (<10%) have distant metastases 

 

In early disease, patients are often asymptomatic. They may present with lower urinary tract symptoms (hesitancy, nocturia, frequency).

In late disease, patients may complain of haematuria, dysuria or systemic symptoms of metastasis (usually bone pain, weight loss, weakness – from cord compression, lethargy, etc.)

 

PATHOPHYSIOLOGY1,3

High-grade prostatic intraepithelial neoplasia (PIN) is a (pre-malignant) precursor lesion to prostate cancer. It is defined as a non-invasive neoplastic growth of prostatic epithelial cells confined within the ducts or acini.

 

Prostate cancers mostly originate in the peripheral zone.

 

Investigations

Digital rectal examination (DRE)

Initial assessment, only detects tumours in the postero-lateral aspect of the prostate. Abnormal findings: nodularity, asymmetry, or induration. However, may fail to detect small tumours (T1) or those located in other parts of the prostate.

Prostate specific antigen (PSA)  

A serine protease produced specifically by prostatic cells. However, it is not specific for cancer and levels can be increased in benign prostatic hyperplasia (BPH), prostatitis, trauma etc. 

Transrectal ultrasound (TRUS) with needle biopsy

With antibiotic coverage (ciprofloxacin), 10 to 12 biopsies are taken under local anaesthetic (periprostatic block).  

 

When prostate cancer is suspected with DRE and/or PSA, histological confirmation with biopsy is required.

 

treatment4

Treatment is based on:

  • NCCN risk category (determined by tumour size – T, PSA and Gleason Score), 

  • Survival (<10 years or >10 years)

  • Patient preference

Conservative

Active surveillance 

Low risk patients with a life expectancy of >10 years 

Curative intent, to reduce toxicity of overtreatment with affecting survival 

Involves close monitoring and actively treating patients once they show signs of progression but still remain stable

Watchful waiting 

All patients with a life expectancy of <10 years 

Palliative intent, aims to minimise side effects from therapy and to avoid/delay treatment 

Symptom guided therapy i.e treating patients once they develop local or widespread symptoms to maintain quality of life

Surgical

Radical prostatectomy 

 

Resection of prostate gland, both seminal vesicles and marginal tissue 

 

Can be achieved with open (retropubic/perineal), laparoscopic or robot-assisted surgery

 

Pelvic lymph node dissection can be carried out in high risk patients

 

Aim for negative margins without compromising continence and potency (erectile function)

medical

Radiotherapy 

 

External beam radiation therapy 

 

Involves delivering focused external radiation to cancerous prostate

 

Recommended standard: intensity-modulated radiotherapy (IMRT) + image guided radiotherapy (IGRT) to reduce damage to surrounding pelvic organs.

 

Bradytherapy 

 

Low dose rate 

Trans-perineal implantation of radioactive sources (seeds) permanently into the prostate gland

 

High dose rate 

Placing a radioactive source into the prostate via a trans-perineal catheter (which can be removed post-treatment)

 

GnRH antagonist

 

E.g., degarelix

MOA: binds to pituitary LHRH receptors 🡪 fast decrease in LH, FSH & testosterone levels

No transient testosterone increase

 

Anti-androgens 

E.g., bicalutamide, flutamide

MOA: non-steroidal anti-androgens.

Binds to androgen receptors and prevents action of endogenous/exogenous testosterone

 

Chemotherapy 
 

Usually for advanced (metastatic) castrate-resistant prostate cancer

 

First line: docetaxel

MOA: Antineoplastic agents; interferes with cellular microtubule network.

Usually for advanced (metastatic) castrate-resistant prostate cancer

 

First line: docetaxel

MOA: Antineoplastic agents; interferes with cellular microtubule network.

 
 

EPIDEMIOLOGY

By the age of 80, 80% of men will be affected however only around 4% will die from the disease

 

REFERENCES

  1. BMJ Best Practice – Prostate Cancer. 

  2. MDT Guidance for Managing Prostate Cancer – September 2013”, produced by: British Uro-oncology Group (BUG) and British Association of Urological Surgeons (BAUS) Section of Oncology. 

  3. EAU-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer (2017). 

  4. UpToDate – Clinical presentation and diagnosis of prostate cancer. 

  5. UpToDate – Precancerous lesions of the prostate: Pathology and clinical implications. 

  6. UpToDate – Genetic risk factors for prostate cancer. 

  7. UpToDate – Risk factors for prostate cancer. 

  8. UpToDate – Interpretation of prostate biopsy.