PSA refers to Prostate Specific Antigen, a protein that is produced in the prostate and that enters both the bloodstream and the semen. First identified in 1982, this protein is easily measured by a simple blood test that has now become routine throughout the world. Over the past 20 years since PSA testing has become mainstream, the diagnosis and treatment of prostate cancer has been revolutionised.
PSA can be produced by both normal and cancerous cells within the prostate. However, cancerous cells “leak” more PSA into the bloodstream. Therefore, the level of PSA correlates with the underlying risk a given man has of harbouring prostate cancer. Because normal cells also produce PSA, it is by no means a perfect test to identify those with prostate cancer. However, there is no doubt that the advent of PSA testing has enabled prostate cancers to be diagnosed at an earlier, potentially curable stage.
Because of its limitations, the PSA is not a stand-alone test in the identification of men at high risk of harbouring prostate cancer. All men having their PSA level measured should also have a prostate examination performed after the blood test. A small percentage of men with a normal PSA level may still have prostate cancer that can be picked up by a properly performed prostate examination. In addition, the way the prostate feels gives important prognostic information for those with a high PSA level who may harbour cancer.
If the PSA is consistently above the normal level (see below) or the prostate feels abnormal, a prostate biopsy is performed to confirm the presence or absence of prostate cancer.
Further information is available about prostate biopsy.
Preparing for a PSA test
In order to make the PSA test as accurate as possible, it is important that you have not ejaculated for 3-4 days prior to the test. Ejaculation is known to raise the PSA level. You should also ensure that you have not had symptoms of a urinary tract infection for at least 2 months before the test. These symptoms include fever, frequency of urination or burning when passing urine. It is also preferable that you have not had a viral illness for 4-6 weeks prior to the test. Each of these may raise the PSA and cause confusion with prostate cancer.
The Normal PSA Level
As outlined above, normal prostate cells also produce PSA. Therefore, as the prostate enlarges naturally with age, we would expect that more PSA is released into the bloodstream, even if no cancer is present. For this reason, Age-based normal ranges for PSA are used. These values are as follows:
|Age range||Median PSA (ng/ml)||Upper Limit of Normal (ng/ml)|
Studies have shown that men whose PSA lies between the Median level and the upper limit of normal at a higher long-term risk of prostate cancer than those with PSA below the median.
The graph on the right gives an indication of the risk of prostate cancer based on the initial PSA, the findings on digital examination of the prostate and the family history of the patient. For example, at a PSA of 4ng/ml, even if the prostate feels normal and there is no family history of prostate cancer, the risk of prostate cancer is over 30%. [Source: Journal of the National Cancer Institute 2006;98:529-34.]
Making the PSA test more accurate
More than 25% of men with a PSA between the upper limit of normal (see above) and 10ng/ml have prostate cancer. Therefore, a significant majority of men with an “abnormal” PSA will undergo an unnecessary prostate biopsy. Conversely, up to 20% of men who have prostate cancer actually have a PSA below the “normal level”. We are therefore faced with a challenge: to avoid unnecessary biopsies in those with an abnormal PSA and pick up cancers in those with a normal PSA. Two strategies are in common use to help us:
Measure the rate of change of PSA over time (PSA Velocity)
If the PSA rises faster than the rate at which it is expected to rise with natural growth of the prostate with age, this indicates a higher risk of underlying cancer. For men with a PSA less than 4.0, a rise of >0.35/year is a concern. For those with a PSA above 4.0, a rise of >0.75 is a concern. Conversely, if the PSA is slightly above normal (say 5.0 in a 60 year old man) but it remains unchanged year after year, we are less concerned.
Measure the percentage of “free” PSA in the blood (by routine blood test)
A portion of the PSA protein circulates in the bloodstream unbound to other proteins. This is called the “free” PSA. If the percentage of free PSA is less than 10% of the total PSA level, this indicates a higher risk of underlying cancer. Conversely, if the free percentage is greater than 30%, we are less concerned.
What happens if your PSA is elevated
It is important to remember that an elevated PSA does not necessarily mean that you have prostate cancer. A series of important steps must be completed before a definitive diagnosis is made. Precisely which of these steps are needed will depend on the individual case.
- Check that there is no other obvious cause for the elevated PSA. A urinary tract infection is a common non-cancerous cause of an abnormal PSA. A simple urine test will exclude this as a cause.
- Perform a prostate examination. It is always important that a prostate examination is performed. If the prostate feels abnormal, a biopsy will be recommended.
- Repeat the PSA test. This is especially important if the prostate examination is normal and this is your first PSA test. Before the next test, it is vital that you do not ejaculate for 3-4 days.
- Proceed to a prostate biopsy. If the prostate examination is abnormal or the PSA is consistently abnormal, a biopsy is required to determine if cancer is present.
What happens if your biopsy is negative
Remember that most men with a moderately elevated PSA (in the range 4-10 ng/ml) do not have a positive prostate biopsy. These men with an “abnormal” PSA but a negative biopsy still need to be monitored. This is because biopsies are also not perfect. They may miss cancer, albeit fairly rarely if more than 14 specimens are taken from the prostate. To be extra cautious, the PSA should be monitored every 6-12 months. The prostate should also be examined each year. If it continues to rise at a high rate, repeat biopsies may be required.
Other important points about the PSA test:
- The higher the PSA, the greater the likelihood that prostate cancer has extended beyond the prostate.
- The faster the PSA doubles in the 1-2 years before treatment for prostate cancer, the worse is the prognosis for that patient.
It is therefore important that a high or rapidly rising PSA is thoroughly investigated to exclude prostate cancer.
Diagnosis and Staging
Prostate cancer can only be diagnosed by obtaining a specimen of the prostate. If the PSA is higher than expected for age, or if the prostate feels abnormal during physical examination, a Transrectal Ultrasound Guided (TRUS) Biopsy of the Prostate may be recommended. This procedure takes 15-20 mins and may be performed under local anaesthetic or with sedation. Most men experience no significant problems after a TRUS biopsy although as with any procedure, side effects may occur.
- Blood in the semen (occurs in almost all men, and will usually disappear within 2-6 weeks)
- Blood in the urine (usually lasts for 1-2 days only)
- Blood in the bowel motions
- Urinary tract infection (antibiotics are given before, during and after the procedure to minimize the risk).
Likelihood of Detecting Cancer by the TRUS Biopsy
The chance of a detecting cancer can be estimated before the biopsy. By combining the PSA result and findings on prostate examination, studies have estimated the risk as follows:
|Prostate Examination||PSA 2-4ng/ml||PSA 4-10ng/ml||PSA >10ng/ml|
If an extended biopsy strategy is used (more than 10 specimens taken from the prostate), the detection rate of cancer is as high as 30-40%, even when the prostate feels normal and the PSA is between 4-10ng/ml.
Grading Prostate Cancer
It is well known that the microscopic appearance of prostate cancer correlates closely with its behaviour. The Gleason grading system is used by pathologists to describe how aggressive prostate cancer appears under the microscope. The pathologist identifies the 2 most common patterns of cancer in the biopsy specimens and assigns each pattern a score from 1 (the least aggressive type) to 5 (the most aggressive type). The 2 scores are then added together to give a final number out of 10, the Gleason sum.
As a general guide, the level of aggression of prostate cancer can be correlated with the Gleason Sum as follows:
|Gleason Sum of Prostate Cancer (Out of 10)||Level of Aggressive Behaviour|
Staging Prostate Cancer
Once the diagnosis has been made, it is important to define how far prostate cancer has progressed. This has critically important implications in the decision making process when treatment options are being considered.
Prostate cancer is staged by physical examination findings and radiology investigations.
Transrectal examination of the prostate. The findings of transrectal prostate examination with a gloved finger form the basis of local staging of prostate cancer (See Diagram). Once prostate cancer is palpable (Stage T2 or higher) the likelihood that cancer cells have grown outside the capsule of the prostate is higher.
- CAT Scan. This is used to help determine if cancer has spread to lymph glands or other organs.
- Bone Scan. Prostate cancer may spread to the spine or pelvic bones. Once this has occurred, the cancer is no longer curable. Bone involvement is unlikely unless the PSA is >40ng/ml.
MRI scan. This study can more accurately determine if prostate cancer has grown outside the prostate. It is a useful test prior to proposed surgery if there is doubt as to whether the cancer is curable by surgery alone (See picture)
|T1||Cancer is not palpable. Biopsy is only undertaken because of an elevated PSA|
|T2||Cancer is palpable but appears to be confined to the prostate gland|
|T3||Cancer is palpable and appears to extend outside the prostate gland|
|T4||Cancer is palpable and appears to extend outside the prostate to involve surounding structures|
Prostate Cancer Prevention
An enormous body of research has been conducted into agents which may reduce the risk of prostate cancer. In recent years, some large prospective studies have been published which shed some light on this issue.
5?-Reductase Inhibitor Medications
Perhaps the strongest evidence for the ability of a single agent to reduce the risk of prostate cancer diagnosis comes from the Prostate Cancer Prevention Trial (PCPT)1, initially published in 2003. In this large-scale trial, more than 18000 men over the age of 50 were randomised to receive placebo or Finasteride (Proscar). This drug inhibits testosterone production in the prostate, leading to a gradual shrinkage of the gland and a reduction in the PSA level. After 7 years, men taking Finasteride were 25% less likely to be diagnosed with prostate cancer. Maximum risk reductions were seen in men with very low PSA levels upon commencement of the medication.
Despite fairly conclusive initial results, several eminent authorities continue to call into question the efficacy and safety of Finasteride with regards to prostate cancer prevention. Some believe that because Finasteride reduces PSA levels, patients may be lulled into a false sense of security and delay having a prostate biopsy until it may be too late2. It is worthy to note that despite the initial results of the PCPT trial, Finasteride is not approved by the US Food and Drug administration or the Australian TGA as safe or effective in preventing prostate cancer.
Further research in prostate cancer prevention is being conducted using other drugs in this class. Results of another major study, the REDUCE trial were presented at the 2009 AUA meeting. There was a 23% reduction in cancer cases over 4 years in men taking the 5?-Reductase inhibitor Dutasteride compared to placebo. Unlike the Finasteride study, the substantial reduction in the risk of prostate cancer was seen in men with levels of PSA as high as 10ng/ml upon commencement of the medication.
Despite these encouraging results, concerns have been raised about the possible association between long-term use of these medications and the development of high-grade prostate cancers. For this reason, it is important to discuss the use of this class of drug with your specialist before considering its use for prostate cancer prevention.
1. Thompson IM et al. The influence of finasteride on the development of prostate cancer. N Eng J Med 2003; 349:215.
2. Walsh PC. Three considerations before advising 5?-reductase inhibitors for chemoprevention. JCO 2009: 27:e22.
Vitamins and Selenium
Initial enthusiasm for the cancer preventive properties of Vitamin E and Selenium came from studies published in the 1990’s which showed prostate cancer risk reductions of 63% for selenized yeast and 32% for Vitamin E. This prompted the design of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to definitively determine whether these agents, alone or in combination, could prevent prostate cancer. Incorporating more than 35,000 healthy men randomly administered selenium, vitamin E, both or placebo, this study showed that after 5.4 years of follow-up, neither agent alone or in combination prevents prostate cancer1. Of concern was the finding that men taking Vitamin E had a slightly increased risk of prostate cancer.
Another recent randomized study has shown that neither Vitamin C nor Vitamin E supplements reduced the risk of prostate cancer2.
1. Lippman SM et al. Effect of Selenium and Vitamin E on risk of prostate cancer and other cancers. JAMA 2009;301(1):39.
2. Gaziano JM et al. Vitamins E and C in the prevention of prostate and total cancer in men. JAMA 2009; 301(1):52.
Reducing Saturated Fats
It is well known that a diet high in saturated animal fats has adverse effects on the cardiovascular system. A large body of evidence supports the notion that a diet high in saturated fats may also increase the risk of a number of cancers, including prostate cancer. Men who migrate from countries with a diet low in saturated fat to a diet high in saturated fat increase their risk of developing prostate cancer. Our laboratory based research in the University of Sydney has conclusively demonstrated the growth-promoting effects of the products of fat metabolism on prostate cancer cells.
It is safe to advise a man wishing to reduce his risk of prostate cancer that limiting the intake of foods high in saturated fats is an excellent place to start.
Other Dietary Advice
Limited evidence exists for a relationship between prostate cancer risk and the following:
- Lycopenes (cooked tomato products)
- Soy Products
- Green Tea
It has been known for over 60 years that the androgen (male hormone) Testosterone, is the key to growth of the prostate gland and forms one of the main “foods” for prostate cancer cell growth.
So-called Androgen Deprivation Therapy has been one of the cornerstones of treatment of advanced prostate cancer for decades. Initially, androgen deprivation could only be achieved by surgical castration. Today, there are many ways in which androgen deprivation can be achieved. Medical castration can be achieved by blocking production of testosterone by the testes. Drugs that achieve this are administered by injection on a periodic basis. Alternatively, the action of testosterone and other androgens on prostate cancer cells can be blocked by a class of drug known as antiandogens. These are taken in tablet form. In some patients, medical castration and antiandrogen therapy are administered together to completely deprive prostate cancer cells of any exposure to male hormones.
|Drug Name||Dosing Schedule||Administration|
|Eligard (Leuprorelin)||1,3,4,6 Monthly||Subcutaneous|
|Lucrin (Leuprorelin)||1,3,4 Monthly||Intramuscular|
|Zoladex (Goserelin)||1,3 Monthly||Subcutaneous|
Whilst androgen deprivation causes shrinkage and regression of prostate cancer cells, it is not a curative treatment for prostate cancer. This is because some prostate cancer cells can replicate without the need for androgens. It is also possible that some cells adapt to the loss of testosterone and use other molecules for growth. Eventually, as these cells take over the cancer once again grows rapidly. This is a state known as Hormone Refractory Prostate Cancer (HRPC). The time between initiation of androgen deprivation therapy and the onset of HRPC varies greatly between individuals. Once this stage has been reached, various manipulations of the medications used to suppress testosterone may transiently reduce prostate cancer growth. However, most patients will ultimately require second-line treatment with chemotherapy.
Situations where Androgen Deprivation therapy is used
Metastatic prostate cancer
This is the most common indication for androgen deprivation therapy. Deposits of prostate cancer in the spine can cause pain and eventually damage the spinal cord. Androgen deprivation shrinks these deposits, reduces pain and the likelihood of spinal cord problems. There is general consensus that androgen deprivation should be commenced immediately if spinal metastatic prostate cancer is diagnosed.
Locally advanced prostate cancer
Patients with stage T3 or T4 prostate cancer can experience bleeding and difficulty passing urine. Androgen deprivation will cause shrinkage of the prostate and can overcome some of these problems. There is also a large body of evidence to show that patients receiving radiation therapy for Stage T3 prostate cancer will have a better outcome if androgen deprivation therapy is used in conjunction with the radiotherapy.
Some patients with locally advanced but non-metastatic prostate cancer who are not candidates for curative treatment such as radiotherapy may not require immediate androgen deprivation. Recent studies suggest that commencement of treatment may be postponed and reserved for men once the PSA reaches 50ng/ml or the PSA is rising rapidly (doubling time less than 12 months)1.Withholding androgen deprivation, or watchful waiting, may help avoid the side effects of long term testosterone deprivation.
Rising PSA after attempted curative treatment with radical prostatectomy or radiotherapy.
After surgery for prostate cancer, the PSA should become undetectable. A rising PSA after surgery (or radiotherapy) often indicates cancer recurrence. If there is a strong suspicion that cancer recurrence has occurred due to spread beyond the pelvis (eg a rapidly rising PSA very soon after surgery) androgen deprivation may be required.
Side Effects of Androgen Deprivation therapy
Recent research has highlighted the potential side effects of Testosterone deprivation. Important side effects include:
A sudden intense heat sensation in the face, neck and upper body. This is reported to occur in more than 80% of men. They may occur spontaneously but are often triggered by stress, hot or spicy foods and temperature changes.
Hot flushes can be reduced by avoiding triggers and the addition of steroidal-based antiandrogens such as cyproterone (Androcur).
Androgen deprivation is associated with a reduction in bone mineral density. Recent studies show that men with prostate cancer receiving androgen deprivation therapy are significantly more likely to suffer a hip fracture compared with those who do not.
Osteoporosis can be reduced by taking a calcium (1200mg/day) and vitamin D (800iu/day) supplement, maintaining a healthy exercise regimen and avoiding smoking. For men with established osteoporosis or those who have had fractures, drugs to increase bone mineral density (bisphosphanates) are used.
Sex hormones play an important role in the balance between muscle mass and fat deposition. Suppression of testosterone causes reduced muscle mass and increased fat deposition, a condition called “sarcopenic obesity”. There is mounting evidence that this is associated with an increased risk of heart disease and that the increased risk is seen even after a short duration (4-6 months) of androgen deprivation therapy.
It is advised that men with other cardiovascular risk factors undergo a thorough cardiology assessment before starting androgen deprivation
Loss of libido and erectile dysfunction
Over 80% of men report loss of erections and libido by 1 year after androgen deprivation therapy.
Medications such as Cialis, Viagra and Levitra have been used with success in this setting. For men who do not respond well to these agents, direct injection of vasodilator medications into the penis (intracavernosal injection therapy) have a high rate of efficacy.
Within 3-6 months of initiating androgen deprivation therapy, many men report reduced concentration and memory. Some studies also report increased anxiety, fatigue and irritability in these men.
It is important for family members to be aware of these changes and help the patient adapt to these side effects.
Intermittent Androgen Deprivation Therapy
In an attempt to overcome some side effects of androgen deprivation, and to possibly prolong the responsiveness of prostate cancer cells to the testosterone-deficient environment, several studies have explored the notion of re-exposure of the patient to androgens. Intermittent androgen deprivation involves withdrawal of medical castration after a 9-12 month period of androgen suppression. The PSA is monitored closely after the medication is withdrawn and reintroduced once the PSA reaches a pre-determined level ranging from 4-20ng/ml.
Several studies have demonstrated an improved quality of life in patients treated with intermittent therapy. In addition, a recently published European randomised study involving more than 600 men with locally advanced or metastatic prostate cancer revealed no difference in survival between patients treated with continuous versus intermittent androgen deprivation2. Whilst the number of prostate cancer deaths were higher in the intermittent group, this was offset by a lower cardiac death rate among these patients. Those treated with intermittent therapy experienced fewer side effects and better sexual function.
- Studer et al. European Urology 2008: 53;941-9.
- Calais da Silva et al. European Urology 2009:55(6);1269-77.
Surgical removal of the prostate remains the gold-standard curative treatment for men with clinically organ-confined prostate cancer. With successful removal of the cancerous organ, many of the long-term effects of other treatment modalities such as radiation therapy are avoided.
The operation involves complete removal of the prostate and seminal vesicles. Because the prostate forms part of the urethra, the “gap” that results is bridged by joining the neck of the bladder to the urethra. In addition, lymph nodes close to the prostate are usually removed to determine if cancer has spread beyond the gland.
Potency and Radical Prostatectomy
Common to all treatments for prostate cancer is the high potential for post-treatment erectile dysfunction. This is due in part to the inevitable effect all treatments have on the tiny, microscopic nerve fibres that control the erectile process (the neurovascular bundle). Works published in the early 1980’s shed light on the anatomy of the prostate and the location of these nerves. This has enabled us to preserve these structures and increase the probability that erections are preserved or at least recover after surgery. However, preservation of these nerves (so-called nerve sparing surgery) DOES NOT guarantee preservation of erectile function. In addition, sparing the neurovascular bundle requires dissection extremely close to the cancerous prostate. This may increase the risk of leaving cancer behind. Therefore, patients with higher grade cancers (Gleason sum 7/10 and higher) and those with more extensive local disease (stage T2 and higher) may not be ideal candidates for total nerve sparing surgery.
There are many ways that erectile dysfunction can be treated. Many men who undergo a bilateral nerve-sparing procedure will respond well to medications such as Viagra. Those who do not will usually achieve good erections with the use of injections of medications such as Caverject directly into the side of the penis. Contrary to popular belief, this is an easy and effective way to achieve very good erections after cancer surgery. For the approximately 20% of men who do not achieve satisfactory erections despite these measures, an Implantable Penile Prosthesis is an excellent and reliable way to overcome erectile problems after prostate cancer surgery.
Overall, despite major improvements in surgical technique and our understanding of anatomy, the majority of men will experience at least some degree of erectile dysfunction after prostate cancer surgery. The good news is that help is available and it should not mean an end to sexual relations.
Continence and Radical Prostatectomy
Perhaps the most concerning side effect of prostate cancer surgery is the potential for long term problems with urinary leakage. The good news is that this is far less common than erectile dysfunction. The vast majority of men (well over 90%) will regain excellent or complete urinary control after radical prostatectomy. Return of continence occurs after a variable period of time. Many men are dry within days of catheter removal. Others may require the use of continence pads for weeks and sometimes for months. However, by 6-12 months after surgery almost all men are happy with their control and do not need to wear continence pads. For the 1-2% of men with persistent incontinence, implantable devices have been developed to overcome the problem, although a second procedure is required to insert these.
Cancer Cure after Treatment
After the prostate is removed, it undergoes detailed analysis by a specialist pathologist. The prostate is painted with ink and sliced very finely. The pathologist will look at the Grade of the cancer, which may be different to the grade initially indicated by the biopsy specimens. In addition, a search will be made for any sign of cancer cells in contact with the ink. The presence of cancer in contact with the ink (so-called “positive surgical margin”) may imply an increased risk of cancer recurrence in the future. The incidence of positive surgical margins with T1-2 cancers is less than 10% in experienced hands. For T3 cancers, where cells have already escaped from the prostate, positive surgical margins are far more common. Depending on the pathological features, additional radiotherapy may be recommended.
Once the final pathology analysis is complete, an accurate assessment of the risk of cancer relapse can be made. For this purpose, statistical computer-based programs (Nomograms) have been developed. This will be discussed with the patient in detail during the follow-up period.
Surgical Approach to Radical Prostatectomy
With refinements in surgical technique and an improved understanding of prostatic anatomy, the Open Radical Prostatectomy has become a very safe and reproducible technique with excellent functional and oncological outcomes. The need for transfusion is less than 5% in experienced hands, postoperative pain is minimal (Sved et al. Urology 2005;65(3):509-12) and hospital stay is 3-5 days in many high volume centres.
Despite this, the endless search for more sophisticated technology has prompted the development of techniques such as robotic-assisted radical prostatectomy (RaRP), with the promise of improved outcomes for prostate cancer patients. Without high-level evidence, the extremely expensive RaRP has been extensively marketed, especially in the USA. A recent review revealed no difference in continence, potency or length of hospital stay between open and RaRP techniques (Brandina et al. Curr Opin Urol 2009; 19:290-296). Regarding positive surgical margins, there is evidence that in experienced hands rates are also similar with higher rates seen during the learning curve of RaRP. Given that many men pay exceedingly high out-of-pocket expenses for the RaRP, it is not surprising that a recent study revealed that men who undergo RaRP are three to four times more likely to be regretful and dissatisfied compared with men who chose to undergo open radical prostatectomy (Schroeck et al. Eur Urol 2008; 54:785-793).
External Beam Radiotherapy
Radiotherapy has been used for many years for the treatment of prostate cancer. Because of this, the side effects are well known as are the expected treatment outcomes.
External beam radiotherapy (EBRT) is usually delivered in 30-40 short treatments, or “fractions” over a period of 6-7 weeks.
When used to treat low-risk prostate cancers (Gleason Grade 6/10, PSA less than 10ng/ml), EBRT can be administered on its own with 5-year cancer-free rates similar to surgery. When used to treat higher risk cancers, EBRT may be combined with hormone ablation therapy to improve success rates.
EBRT has the advantage of the avoidance of major surgery, so is a better management option in the patient for whom major surgery poses a significant risk. EBRT with or without hormone ablation is an excellent option in cases where cancer is believed to have extended just beyond the prostate (Stage T3 disease). Because there is a lower risk of urinary incontinence with EBRT compared to surgery, this is a better option for those at greater risk of incontinence (eg previous prostate surgery) or for those who would not accept the risk of incontinence.
EBRT has some disadvantages to surgery for treatment of localised (T1-2) disease. If there is evidence of cancer recurrence after surgery, EBRT can often be used as a second-line treatment. Unfortunately, if cancer recurs after radiotherapy, surgery as a backup second-line option is either not possible or carries with it an unacceptably high risk of complications. For that reason, when a man has a life expectancy of greater than 10 years and has localised cancer (T1-2 disease), surgery is usually considered the first line treatment option.
Side Effects of EBRT
- Tiredness that may last for several weeks
- Erectile dysfunction (50% at 5 years)
- Rectal damage from radiation scatter (2-3%)
- Possible risk of secondary cancers (in rectum and bladder). Incidence estimated at 1/70 in men who survive more than 10 years after receiving radiotherapy (Bostrom and Soloway Eur Urol. 2007 Oct;52(4):973-82).
Low-Dose Rate (Seed) Brachytherapy
This form of radiotherapy involves the implantation of radioactive seeds directly into the prostate. Unlike EBRT, Seed Brachytherapy usually requires only an overnight stay in hospital at most. The seeds are implanted through the skin of the perineum into the prostate. Because the radiation is delivered within the prostate, nearby structures such as the rectum are less likely to be affected.
Seed brachytherapy has proved to be a very effective form of treatment for selected men with prostate cancer. Cancer control rates in patients with a PSA
Seed brachytherapy is best used in men with smaller prostates (<40cc) and those with minimal “prostate symptoms” such as poor flow, dribbling, frequency and urgency. Prior to seed implantation, a detailed ultrasound study of the prostate is performed to obtain an accurate estimation of the prostate size. Men who have had previous prostate surgery or are deemed at high risk of eventually needing prostate surgery should avoid seed brachytherpay due to the high risk of urinary incontinence when the two procedures are combined. Men who receive seed brachytherapy alone almost never suffer urinary incontinence.
Side Effects of Seed Brachytherapy
- Urinary symptoms are common in the first 8-12 weeks after implantation. These may consist of poor flow, burning, frequency, and waking at night to pass urine. These symptoms may persist over 6 months in 10% of patients.
- Blood may appear in the urine and sperm. This usually settles within a few weeks.
- Erectile dysfunction. As with all treatments for prostate cancer, brachytherapy may impair the ability to gain a natural erection. This occurs in about 50-60% of men by 5 years. Many men will be able to achieve erections with the help of medications such as Viagra.
- Urethral stricture. Due to the high levels of radiation focussed on the prostate, scarring may develop in the urethra. This may cause slowing of the flow of urine. Surgery to correct this may be necessary. The incidence of stricture is about 5%.
High Dose Rate Brachytherapy
Quite different to seed brachytherapy, high dose rate (HDR) brachytherapy involves the placement of 18-20 hollow needles into the prostate under general anaesthetic through which radiation is placed. This part of the treatment is delivered in 2 sessions, usually 2 weeks apart. You are only required to stay in hospital for the day of each treatment (730am to 5pm). Following these 2HDR brachytherapy boosts, a moderate dose (23 treatments) of external beam radiotherapy is administered.
HDR brachytherapy has been used with good success in men with a variety of grades and stages of prostate cancer. It is particularly well suited to the treatment of men with stage T3 cancer. In these patients, there is a higher risk of incomplete cancer removal if surgery is undertaken. In addition to the radiation therapy itself, many patients with stage T3 prostate cancer receive hormonal therapy for a variable period of time. This has been shown to improve cancer free survival in these patients.
Side Effects of HDR Brachytherapy
- Urinary frequency, urgency and slowing of the stream for several weeks. You may also see traces of blood in the urine.
- Bowel movements may be urgent for several weeks or in rare cases, this may be permanent.
- Long term problems with blood in the bowel motions or urine may occur in 1/20 patients. Other treatments such as laser coagulation of bleeding blood vessels may be required.
- Scarring (stricture) of the bladder neck leading to poor flow of urine may rarely occur.
- Erectile dysfunction may occur in approximately 50% of men.
Decision Making – Putting it all together
In order to make the most informed decision about which treatment is best for the prostate cancer patient, a number of factors must be taken into account.
- The Age and Health Status of the Patient
- The Stage of the Disease
- The PSA at Diagnosis
- The Gleason Sum of the Cancer
- The Priorities of the Patient
The Age and Health Status of the Patient
Of all the factors which influence our decision regarding the most appropriate management option for the individual man, this is perhaps the most important. It is true to say that many men will die with and not of prostate cancer. However, it is not possible to give an individual patient an assurance that he will come to no harm from his cancer. A landmark study has shown that men aged 50-65 with intermediate grade (Gleason sum 7/10), localized cancer have a 60-80% chance of dying of their disease within 20 years of diagnosis if treated without curative intent. In contrast, the risk of prostate cancer death drops to 30% in a man aged 70-75 who is diagnosed with a Gleason sum 6/10 cancer (Albertsen et al, JAMA 2005;293:2095-2101.) Therefore, we tend to treat younger men with higher grade disease more aggressively in fear that the cancer will ultimately cause them harm.
In addition, various treatments may have different side effects depending on patient age. For example, the risk of urinary incontinence or erectile dysfunction after prostate cancer surgery is likely to be higher in a given 75 year old man than in a 50 year old man.
The Stage of the Disease
Whilst rectal examination of the prostate on its own is a relatively crude staging test, it has been well established that by the time prostate cancer becomes palpable (Stage T2) almost 50% of cancers have already grown out of the prostate, even if only microscopically. By the time they are suspected to have extended beyond the prostate (Stage T3), 80% have indeed grown out of the prostate. This will have implications in choosing the best form of therapy that is most likely to adequately treat the local disease.
The PSA at Diagnosis
As the PSA rises, the risk of cancer growth beyond the prostate increases. Whilst 80% of men have organ-confined disease if their PSA is below 4ng/ml at the time of diagnosis, 50% of men will have cancer that has grown outside the prostate if the PSA has risen above 10ng/ml. By the time the PSA has risen over 20ng/ml, 20% of men will have cancer that has spread to the lymph nodes. Therefore, surgery alone is rarely offered to men with a PSA close to 20ng/ml, because of the high chance that it will not succeed in removing all of the cancer.
The Gleason Sum of the Cancer
Higher Gleason grade tumours (grade 8-10 out of 10) are more likely to have extended outside the prostate, especially if the cancer is palpable (Stages T2-T3). This means, for example, that surgery alone is less likely to completely eradicate the disease. In these cases, the patient must be aware that combination treatments such as surgery plus radiotherapy or hormone therapy plus radiotherapy may be the best option. In contrast, a lower Gleason sum tumour (6 out of 10), especially if it is not palpable (Stage T1) can most probably be cured by one treatment alone.
The Priorities of the Patient
Ultimately, the patient will be in control of his treatment. Each treatment for prostate cancer carries with it its own potential side effects. For example, radical prostatectomy is associated with a small but real risk of urinary incontinence. If a man does not wish to expose himself to this, a form of radiotherapy would be a better option for him.
Putting It All Together
Overall, the decision about the most appropriate form of management for the individual with prostate cancer can only be made when all of the above factors are taken into account. In order to simplify this process and give the patient the most accurate prognostic information, medical statisticians have developed computer-based Nomograms. These have been formulated after the analysis of the outcomes of thousands of men who have undergone treatment for prostate cancer. Nomograms allow the patient or doctor to enter the information available (such as the PSA, Gleason Grade, clinical stage etc) and estimate the outcome of various treatments such as surgery and radiotherapy.