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Prostate Cancer

5 Key points:

  • Prostate cancer is now detected at an early stage as a result of health screening
  • The diagnosis is suspected when the PSA is > 4 ug/L and confirmed from prostate biopsies
  • MRI can be done prior to biopsy to look for suspicious areas and facilitate fusion biopsy
  • Treatment choices vary from active surveillance, surgery to radiotherapy.
  • Surgery still gives the best cure rate ( > 90% cure ) and the robotic method is now the preferred choice because of faster recovery of continence, better preservation of potency and lower chance of leaving cancer behind

 

Prostate Cancer is very rare before the age of 50 years. Most cases are detected in men above 60 years old. The exact cause is unknown, as genetic causes account for only 9% of cases. From migration studies, a high fat diet seems to be the common risk factor. Prostate Cancer is now the 3rd commonest cancer in Singapore men. The general statistics imply that this is predominantly a disease of the Western world may not be true anymore. Although epidemiological studies show a wide difference in the incidence between Western and Asian populations, with the fast ageing population and westernised diet, prostate cancer has become more common in Asian men.

Symptoms

In its early stages, prostate cancer does not cause any symptoms. As the cancer progresses, the enlarging tumour compress the urethra, blocking the flow of urine. When this happens, frequent urination and terminal dribbling occur. Occasionally, blood in the urine or semen is the first sign of prostate cancer. As prostate cancer advances, it spreads to the pelvic lymph nodes and the bones to cause bone pain and even fractures.  A late manifestation is spinal cord compression and paralysis.

Stages

Prostate Cancer is classified into its 4 stages [Fig 1].

Figure 1. Stages of Prostate Cancer

In Stage 1, there are no symptoms. The cancer is small volume and cannot be felt with the finger. It usually goes undetected and diagnosed only upon examining the prostatic chips after transurethral prostate (TURP) surgery or at health screening when a high PSA level (> 4 ng/dl) is found.

In Stage 2, prostate cancer can be felt as a tumour on rectal examination. Although the tumour volume is bigger, it is still confined within the prostate and cure still possible.

By Stage 3, the cancer has spread out of the prostate capsule. Common symptoms at this stage include difficult urination. This is now a locally advanced stage and the patient has a lower chance of cure. Treatment is aimed at slowing its spread and preventing bladder blockage. The PSA level is usually > 10 ng/dl at this stage.

At Stage 4, the cancer has already spread beyond the prostate to the lymph nodes and bones. Symptoms at this stage include difficult urination, bone pain, weight loss and fatigue. At this stage, treatment is targeted at preventing further complications and reducing pain. The PSA level is usually > 100 ng/dl by now.

Diagnosis

The most reliable method of diagnosing prostate cancer is a biopsy. This is usually done via the rectum under ultrasound guidance (TRUS) [Fig 2]. Because this procedure carries the risk of infection and bleeding, prophylactic antibiotics are given to reduce this risk to < 5%. Anti-platelet drugs like aspirin and plavix must also be stopped prior to biopsy. It is now standard practice to take at least 12 cores. To reduce pain during the biopsy, local anaesthesia is given by means of a peri-prostatic nerve block.

Fig 2. Prostate biopsy is done under ultrasound guidance

To reduce the risk of infection, the transperineal route can be attempted [Fig 3]. But this requires sedation in addition to local anaesthesia and a different set of biopsy equipment.

Fig 3. Prostate biopsy via the transperineal route

Fig 4. The difference between transrectal and transperineal prostate biopsy

Whichever route is used, the accuracy rate for ultrasound guided biopsy is still in the range of 95%. Multiparametric MRI is increasingly being done to pre-locate the suspicious cancerous areas, and facilitate ultrasound-fusion biopsy method [Fig 5]. This would also reduce the number of biopsy samples (usually up to 20 cores) compared to saturation method where > 30 samples are taken.

Fig 5. Multiparametric MRI – ultrasound fusion biopsy technique

Upon confirmation, further investigations are done to stage the cancer and this is through a pelvic MRI [Fig 6] and a bone scan [Fig 7].

Fig 6. MRI of prostate to assess the location of the tumour and stage of the cancer in the pelvis

Fig 7. Bone scan to detect any spread to the bones

The latest staging modality is a PSMA PET CT scan which is more sensitive than the bone scan and is especially useful for post-treatment cases whose PSA level rise again (biochemical recurrence). [Fig 8].

Fig 8. PSMA PET CT to specifically detect prostate cancer in the whole body

Treatment

Early Prostate Cancer (Stage 1 & 2)

When the tumour is limited to the prostate gland, the cure remains high (> 90% survival). This is achieved through surgery or radiation, but advocated only for men who are expected to have a life-span of 10 years or more, i.e. younger than 75 years.

a) Surgery (Radical Prostatectomy)

Here, the entire prostate containing the tumor is removed [Fig 9]. Pelvic lymph nodes are also sampled if the PSA is > 10 ug/L or the tumour is of high-grade. Complications include excess bleeding, urine leak, impotence and incontinence. A relatively young, otherwise healthy man is an ideal candidate for surgery. The laparoscopic technique is a minimal invasive method of doing radical prostatectomy with the advantage of less pain and faster recovery, but the robotic method is now the gold-standard because of minimal blood loss and better functional outcomes, thanks to the 3-dimentional, magnified vision and articulate robotic arms which help the surgeon to spare the erectile nerves and achieve a water-tight anastomosis of the bladder to the urethra. See article on “Robotic Radical Prostatectomy“.

Fig 9. Radical prostatectomy is the removal of the entire prostate gland

b) Radiation (External beam or Brachytherapy)

Radiation therapy uses high energy X-rays to kill the cancerous cells. There are 2 ways to administer this therapy, either externally (DXT) or internally (brachytherapy). External beam is a daily session lasting 7 weeks. Side-effects include fatigue, skin reaction, frequent urination, diarrhoea and rectal bleeding. Brachytherapy is a 2-step process that involves planting multiple radioactive seeds within the prostate after soft-ware imaging and planning. This is to ensure accurate placement to ensure the whole prostate is covered and minimise seed expulsion out of the urethra [Fig 10]. Long term side effects of radiotherapy are cumulative and include radiation cystitis (bleeding), urinary / faecal incontinence and impotence.

Fig 10. Brachytherapy where radioactive seeds are implanted into the prostate

c) Active Surveillance

Active surveillance is an option based on autopsy studies which showed that many men who died of other illnesses harboured prostate cancer. This is feasible for older men (above 75 years) and those with low-grade, low-volume prostate cancer. The problem with adopting this policy is that as much as 30% of such cancer still progress to aggressive cancers and ultimately require intervention.

Advanced Prostate Cancer (Stage 3 & 4)

Both surgery and radiation can be used either alone or together to treat Stage 3 disease. However, most Stage 3 cancers still require hormonal treatment to suppress the cancer cells that have spread beyond the prostate capsule. In Stage 4, palliation is the only treatment and consists of lowering the testosterone. In the event of painful bone involvement, direct radiation to the bone or biphosphonate drug infusion eg. Zometa, can be given to halt further bony destruction.

Control of the disease is achieved by either reducing the production of testosterone, the hormone that fuels the cancer, or blocking its action. Depriving prostate cancer of testosterone causes it to shrink and this achieved in one of 3 ways:

a) Orchidectomy
This is the surgical removal of the testicles and is a minor operation. As 95% of testosterone is produced by the testes, orchidectomy immediately brings down the testosterone levels to zero.

b) Anti – Androgens

These drugs block the action of testosterone at the cell receptor level. There are many new drugs available and they can be used in combination with other therapies. Side-effects vary from diarrhoea to painful breast enlargement (gynaecomastia). They are costly and have to be taken daily.

c) LHRH analogs

This group of drugs is given by injection under the skin at either monthly or 3 monthly intervals [Fig 11]. They act by depleting testosterone production from the testicles, similar to doing an orchidectomy.

Fig 11. Injection of LHRH drug under the skin

Because advanced prostate cancer causes excess pain and morbidity once it spreads to the bones, early detection is still the best way to prevent events. Because of advancements in medical therapies, men with advanced cancer can now living longer. However, the lifetime cost is higher than treatment for organ-confined prostate cancer.

Summary

Prostate cancer is getting more common and causes excess morbidity and suffering when diagnosed late. Fortunately, there is a tumour marker, PSA which can detect the cancer in its early stages, and also serves as a surrogate marker for effectiveness of treatment and to any recurrence. The threshold for biopsy is 4 ng/dl and while majority of men with high PSA do not have prostate cancer, this is the currently the cheapest and most convenient screening test. There are now various biopsy methods, from standard TRUS to TRUS-MRI fusion method and the option of transperineal route to reduce the risk of infection.

Upon confirmation of organ-confined cancer, surgery still gives the most reliable long-term survival, the gold-standard surgery being robotic prostatectomy.