There are several different treatment options for prostate cancer, and making a decision about what option is best for you can often be confusing. There are no randomised control trials that compare all of the different treatment options to identify which is the best way to manage prostate cancer. Some treatment options are not suitable for some patients, and all treatment options are not 100% effective in curing or containing all prostate cancers.
As a general rule most prostate cancers are slow growing, and so a decision does not have to be made on the first consultation. In fact several consultations may be required to reach a treatment decision, and second opinions may also be required.
One factor which affects what treatment option to proceed with is how aggressive the prostate cancer is. This is determined by the stage of the cancer (the clinical feel of the prostate based on a digital rectal examination), the histological features of the prostate cancer (ie: the Gleason grade), and the pre-treatment PSA. Low risk cancer are typically cancers with a Gleason score 6 or less, a PSA < 10, and a clinical stage <T2b. Intermediate risk cancers are typically cancers with a Gleason score of 7, a PSA between 10-20, and a clinical stage of T2b – T2c. High risk cancer has a Gleason score of 8-10, a PSA > 20, and a clinical stage of T3 or above. Another factor which affects which treatment option to proceed with is the general medical condition of the patient. A patient’s age and co-morbidities at the time of diagnosis help estimate the life expectancy of a patient (ie: if they didn’t have prostate cancer).
The personal preference of the patient is also important, as is the potential side effects of the treatment and their likely impact on the patient’s quality of life.
Active surveillance (AS) is based on the fact that not all prostate cancers are clinically significant and therefore are unlikely to cause problems in the future. AS aims to decrease the overtreatment of insignificant cancers, whilst still monitoring for changes that may suggest progression of the cancer and a need to actively intervene or treat. By not over treating some cancers the obvious advantage is avoiding side effects from that treatment, which may be significant. The downside of AS is that regular blood tests (PSA), digital rectal examinations and prostate biopsies +/- MRI scans will be required. There is the problem of possible anxiety whilst on AS and also a possibility that the cancer may spread outside the prostate before treatment is instigated. The criteria for active surveillance is not well established, but typically it is reserved for patients with low volume, low grade disease (e.g. PSA < 10, T1c cancer and a Gleason score of 6 in a limited number of biopsies). The timing for active intervention is also ill-defined but typically is suggested if the PSA is rapidly rising, the cancer becomes palpable on digital rectal examination, or repeat biopsies show either more extensive cancer or higher grade cancer (e.g. > Gleason 6).
Surgery involves the complete removal of the prostate gland and the seminal vesicles situated behind the prostate for localised cancer this treatment option is highly effective. Surgery is suitable for men who have a life expectancy of > ten years and who have organ-confined (or possibly minimal extra-capsular spread) prostate cancer.
There are different surgical approaches for a radical prostatectomy including open, laparoscopic and robotic-assisted laparoscopic. Each of these options has similar cure rates and similar rates of incontinence and impotence in experienced hands. Post-operative urinary incontinence is partly dependent on the age of the patient. Patients over the age of seventy are at a higher risk of incontinence after surgery. A small percentage of patients can have bothersome incontinence post-operatively which may require further surgery, and some patients may wear ‘confidence’ pads when out in public. The chance of maintaining erectile function after surgery depends on the patient’s age and pre-operative erectile function, as well as whether a nerve sparing operation was performed. Other risks of surgery, apart from incontinence and impotence, include bleeding, infection, rectal or ureteric injury, anastomotic stricture, infertility, and post-operative/anaesthetic complications.
The benefits of robotic and laparoscopic surgery over open surgery include decreased pain, reduced blood loss, a shorter hospital stay, an earlier return to normal daily activities, and a lower incidence of bladder neck contractures.
Surgery does not guarantee cure, and salvage treatments such as radiotherapy or hormonal therapy may be required in the future. Lifelong PSA follow-up will be required after surgery.
Radiotherapy uses ionizing radiation to kill prostate cancer cells. It is offered as a potentially curative treatment option for patients with localised or locally advanced prostate cancer and a life expectancy > ten years. Radiotherapy can be delivered in two ways. The commonest type is external beam radiotherapy (EBRT), where radiation is delivered from a source outside the body. The other option is brachytherapy, where the radioactive source (either seeds with low dose rate or rods with high dose rate) is placed inside the prostate.
EBRT involves daily outpatient treatment sessions. Each session takes ten to fifteen minutes, and is given for five days a week over seven and a half weeks. Most centres offer conformal radiation treatment, but newer treatment options such as intensity modulated radiotherapy (IMRT) are available in some centres. The newer treatment options aim to increase the radiation dose to the cancer but limit the radiation dose to the surrounding normal cells.
Often to help with the accuracy of external beam radiotherapy three fiducial gold seed markers are inserted into the prostate. This is typically done by a Urologist under sedation.
Adjuvant hormone therapy is given to patients with medium or high risk cancer undergoing radiotherapy. This is usually commenced three months prior to starting radiotherapy, and may continue for up to two years. Adjuvant hormone therapy leads to a decreased cancer volume in the prostate, which improve the success rate of radiotherapy.
EBRT, like surgery, can have side effects. These include incontinence, impotence, skin discomfort, tiredness, rectal frequency (e.g. diarrhoea) or bleeding, urinary frequency or urgency, urethral strictures and haematuria (blood in the urine). There is also small risk of developing other cancers in the long term (e.g. rectal or bladder).
One advantage of EBRT is that it avoids the need for a general anaesthetic, which is advantageous in patients who have significant co-morbidities and are unsuitable for a general anaesthetic. EBRT also has the ability to possibly cure cancer that is just outside the prostate capsule, and there is also a slightly less risk of urinary incontinence when compared to surgery.
One of the major downsides of radiotherapy is that repeat radiotherapy cannot be given to the prostate. Also the chance of having salvage surgery after radiotherapy is very low.
Brachytherapy is a form of radiotherapy where the radiation source is placed within the prostate. This allows a higher dose of radiation to be given to the prostate, with the possibility of less radiation damage to surrounding structures such as the rectum and external urinary sphincter.
Low dose rate brachytherapy (LDR) is performed under a general anaesthetic. Approximately sixty or more radioactive iodine 125 seeds are placed into the prostate using small needles inserted through the perineum. The procedure can take around two hours, and the patient is discharged from hospital, catheter free, the following day. The seeds remain in the prostate, but the effects of the radiotherapy gradually wear off over several months.
Men with prostate cancer who are suitable for LDR include those with a PSA of < 10, a relatively small sized prostate, and a Gleason score of 6 or 7. The advantages of LDR over EBRT are that it requires a shorter visit to hospital and it provides a higher dose of radiation to the prostate. Like EBRT the side effects include incontinence, impotence, urethral strictures, irritative voiding symptoms, haematuria, rectal frequency/urgency, urinary retention and per rectal bleeding. Further radiotherapy is not possible after LDR, and salvage surgery is rarely possible.
High dose rate brachytherapy (HDR) involves the placement of small rods into the prostate through the perineum under a general anaesthetic. Through these rods high dose radioactive material is inserted to allow high dose radiation to the prostate. Three treatment sessions are usually given, whilst in hospital, over a twenty-four hour period. The rods are removed after the last session, and the patient is typically discharged from hospital the next day. A further four and a half week course of external beam radiotherapy is usually given after discharge. This form of treatment is typically given to patients with intermediate or high risk cancer, and is often given in conjunction with neo-adjuvant hormone therapy. The side effects of HDR are similar to LDR and EBRT.
Watchful waiting is an established treatment option for elderly men who have low risk prostate cancer and a higher chance of dying from other causes. It is also an option for younger men with significant co-morbidities and an estimated life expectancy of < ten years. It involves regular PSA (and DRE) monitoring, with hormone treatment commencing if the patient has an increasing PSA (total PSA or PSA velocity), bone pain (e.g. secondary to bony metastatic disease), or increasing voiding difficulties (suggestive of local cancer progression). Studies have shown that there is no survival benefit in commencing hormone treatment early or at a delayed time.
Hormonal therapy or androgen deprivation therapy (ADT) is usually offered to patients who have non-curative prostate cancer ie: spread outside the prostate to the lymph nodes or bone. It may also be offered to patients who are deemed not suitable for surgery or radiotherapy, given their age and co-morbidities (ie: decreased life expectancy).
ADT involves stopping the production of testosterone, a hormone produced by the testes, which feeds prostate cancer and causes it to grow and spread. Hormone therapy will reduce prostate cancer throughout the body, including in metastatic sites, but it will not cure the cancer. Some prostate cancer cells unfortunately do not respond to hormone therapy at all.
ADT can be given as a form of chemical castration ie: by taking a tablet up to three times a day, or by having an injection every one, three, four or six months. Another form of ADT is surgical castration ie: the removal of the testes (orchidectomy).
The effectiveness of hormone therapy is typically monitored by regular PSA tests. A reduction in bone pain or obstructive voiding symptoms may also occur.
Some patients are suitable for temporary cessation of hormone therapy (called intermittent hormone therapy). With this approach patient’s testosterone levels gradually increase, and therefore some of the side effects of the ADT will lessen. Hormone therapy is then recommended when the PSA increases above a certain level.
ADT unfortunately may have several side effects, including tiredness, decreased memory, mood or concentration, hot flushes, breast tenderness or enlargement, loss of libido, loss of erections, decreased muscle bulk, decreased bone density (ie: osteoporosis), and increased weight gain/fat deposition. Patients are also more susceptible to increased cholesterol levels and diabetes.
It is important for patients who are commenced on hormone therapy to maintain a regular exercise program and a well-balanced diet, and also to have periodic bone densitometry studies to assess for osteoporosis.