NEW TREATMENTS FOR PROSTATE CANCER HOW DO I CHOOSE?

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1 NEW TREATMENTS FOR PROSTATE CANCER HOW DO I CHOOSE? by Dr Phillip Stricker The following is a summary of a presentation to the St Vincent s Prostate Cancer Support Group on 4 th June 2002 The many new treatments now available for prostate cancer make it more difficult to choose which is the best treatment for you. Options include radical prostatectomy of various forms including nerve sparing, non-nerve sparing and non-nerve sparing with sural nerve graft. It also includes external beam radiotherapy, brachytherapy with seeds, high dose rate brachytherapy delivered though wires, hormone therapy and active surveillance (also known as watchful waiting ). With every individual it is important to discuss all these options including their cure rates, the side effects of their treatment and the individual factors that may influence the choice of treatment. NEW OPTIONS (1) Surgery. The newer therapies for surgery include careful nerve sparing prostate cancer surgery and sural nerve grafting. With nerve sparing surgery it is important that one selects the right cancer to perform this surgery on otherwise one will tend to leave cancer behind. This tends to occur if the cancer has eaten into the nerve tissue. Certain factors relating to the tumour give one an indication as to whether it is suitable or not suitable for nerve sparing surgery. These factors are: the clinical stage, the number of biopsies positive on that side and the presence or absence of perineural invasion. The technique of nerve sparing surgery has become more and more refined and one can more confidently say that one can preserve nerves in patients with the right tumour. Potency rates as high as 80% or 90% can be achieved in young patients who are potent and have very early stage tumours. Sural nerve grafts have now been used when nerves have to be removed. In some cancers, to ensure that the cancer is completely removed, it is safer to remove a nerve on one side than it is to preserve it. In these patients a recent development involving stitching in a nerve from the leg (the sural nerve) can be used. Although this is still fairly experimental it is gaining popularity and with careful surgical technique can be accomplished. Certainly Dr Peter Scardino, one of the pioneers of the technique, has several years of case histories. Only certain people are suitable for this treatment. They are younger patients who are potent and who require one of their nerves to be removed to ensure a high likelihood of clearing the cancer. They must be prepared to accept a relatively experimental procedure and the possibility of some side effects from grafting of the nerve. The technique of nerve sparing and nerve grafting has led to the development of an electrical instrument, known as Caver Map, which can help identify these microscopic erection nerves. This not only helps identify the nerves but also helps predict whether potency will ultimately return.

2 (2) Brachytherapy. Brachytherapy using radioactive seeds is another new therapy which is an option for patients with localised and early prostate cancer. It is only suitable for those with very early stage cancers and Gleason scores less than 7 and a PSA less than 10. The rapid strand system, where the seeds are linked together, can help place seeds on the outside edge of the prostate to ensure the tumour is covered. The technique to do this involves making a volume assessment of the prostate, constructing a template and preparing a plan to place the seeds correctly. Ultimately the procedure places the radioactive seeds in the predetermined position. This therapy gives an excellent outcome if one chooses the right tumour and particularly if patients with severe urinary obstruction are excluded. It tends to be used more in a slightly older group as results are only out to 14 years at this stage. High dose rate brachytherapy is a more invasive new treatment where very high doses of radiotherapy can be placed accurately into the prostate by wires. This therapy is always combined with external beam radiotherapy and is appropriate for more advanced cancers where the PSA is greater than 10, the Gleason score is greater than 7 and the clinical stage is greater than T2B. These cancers generally are difficult to cure with surgery and high dose rate brachytherapy may be more appropriate. (3) Other Treatments. The other options include ordinary radiotherapy, hormone therapy and active surveillance. In older patients with better differentiated tumours, hormone therapy or active surveillance may be the appropriate treatments CURE RATES Special tables or nomograms (known as Kattan Tables) have now been developed which help predict the likely cure rates of each of these different therapies. More information on these tables can be found at SIDE EFFECTS Radical prostatectomy side effects have considerably improved over the last five years. Incontinence is down to very low figures (about 2%) and erectile dysfunction is much less common in selected patients. It has to be understood however that erections may take up to 48 months to return in some cases. Brachytherapy side effects are mainly urinary frequency and urgency. Patients who have a very large prostate or a lot of urinary symptoms before brachytherapy are more likely to suffer a complete urinary block (retention). Existence of these symptoms are a relative contra-indication to its use. Hormone therapy side effects include hot flushes, mood swings, decreased libido, decreased erections, weight gain, lethargy, breast tenderness, and bone loss. All these can be addressed if they become a problem. In particular bone loss can now be prevented by the use of bisphosphonate therapy. FACTORS TO CONSIDER WHEN DECIDING WHAT TREATMENT ONE NEEDS In general there are four factors to consider when deciding on a treatment. These include: 1. Tumour factors 2. Prostate factors 3. Local factors 4. Patient factors

3 1. Tumor factors There are seven tumour factors which will dictate the type of treatment which is best for an individual cancer: the clinical stage, the PSA level, the Gleason score, the position of the cancer, the extent of the cancer, the presence of perineural invasion, and the likelihood of disease penetrating through the capsule are all factors which will influence the choice of therapy. For example, nerve sparing prostatectomy should only be considered in those patients where the cancer is almost certainly confined to the prostate, is not too extensive and of a low clinical stage. On the other hand, brachytherapy seed treatment should only be considered where the PSA is less than 10, the Gleason score is less than 7 and the clinical stage is less than T2B. High dose rate brachytherapy in combination with external beam radiotherapy should be considered where surgery is highly unlikely to cure the cancer such as in patients with very extensive cancer, with a high clinical stage and a PSA between 10 and 30, or where there is a high likelihood of disease penetrating through the capsule - particularly if it is located at the apex, which is difficult to cure surgically. Hormone therapy should be considered where there is extensive local cancer unlikely to be cured such as a T4 tumour or where the PSA is greater than 50. Active surveillance should be considered in less aggressive microscopic tumours where for example only one of many biopsies are involved with a microscopic focus of low grade tumour with a low PSA. 2. Prostate Factors The size and shape of the prostate as well as urinary symptoms may influence decisions. Urinary symptoms include obstruction, irritation and prostatitis. For example, a very large prostate may not be suitable for seed therapy or high dose rate brachytherapy. Furthermore a patient with severe urinary obstruction may not be suitable for any radiotherapy treatment. If a patient has severe bladder irritation it may be wise to avoid radical prostatectomy because these patients often become incontinent after surgery. Prostatitis may, for example, suggest that one shouldn t have seed therapy. 3. Local factors Factors that may influence therapy include previous surgery, previous radiotherapy and the pelvis anatomy such as its shape, the presence of a previous injury or general obesity. Where previous surgery has occurred, such as bowel surgery, this may make further surgery more difficult. Where previous radiotherapy has occurred clearly no further radiotherapy is possible. When a patient is extremely obese he may be better and safer to have a nonsurgical treatment. If a patient has had a fractured pelvis he may be wise to avoid surgery as this would lead to incontinence. 4. Patient factors The patient factors can broadly be grouped into sexual, urinary, bowel, general health, the type of person and other factors.

4 a) Sexual The patient s current sexual status as well as his personal situation in life, ie his relationship and the importance he places on sexual potency are clearly major factors in making a decision. His preparedness to use sexual aids is also an important factor. For example, a man who has recently married a younger partner and wishes to choose the treatment with the lowest chance of sexual side effects would select seed therapy, assuming he has the appropriate tumour. b) Urinary c) Bowel The patient s current status with regard to urinary and irritative symptoms as well as his fear of incontinence may have a bearing on his treatment. For example, if a patient has a particular fear of incontinence then he should not consider surgery. The patient s current bowel status with regard to previous treatment, the presence of underlying bowel problems such as ulcerative colitis or Crohn s disease or irritable bowel symptoms may have a major bearing. If he is particularly fearful of long term bowel side effects such as faecal incontinence, for example, he should not consider radiotherapeutic options. d) General Health The age of the patient and his life expectancy, the presence of longevity in the family, as well as other health problems, the various medications he takes such as Warfarin and the presence of obesity will have an influence on the therapy. For example, if the patient has a life expectancy of less than10 years and has a slow growing tumour he may be better to consider active surveillance. e) Type of Person The type of person the patient is will largely dictate his ultimate choice. Whether he is the worrying type or the accepting type; whether he is a person who needs to make a joint decision with the doctor or he leaves the decision to the doctor; whether he wants it out or has a fear of surgery; whether he is a pragmatic type or has unrealistic expectations of his life expectancy; or whether he is a more conservative or punter type. Finally, there is the natural therapy type. Each different type of patient will bias the decision to one therapy or another. For example, the conservative type will always go for a surgical solution whilst the natural therapy type will go more for active surveillance therapy. The worrier will never accept active surveillance whilst the fear of surgery type will always go for a less invasive therapy. f) Other factors Other factors which may influence patients treatment choices include geographical location, the particular person s personal experience with cancer with a friend or family, the family history and the pattern of the cancer, cultural factors or finances. For example, a son with a strong family history where the father has died of prostate cancer at a young age will tend to choose early and aggressive treatment.

5 IDEAL CASES Every treatment method has an ideal patient. Here are some examples: Nerve sparing radical prostatectomy is ideal for a younger, conservative type patient with normal erections, possibly experiencing urinary obstruction, who has a low volume but high grade tumour. Radical prostatectomy with a sural nerve graft is ideal for a younger patient who has good erections, is anxious to preserve his potency and is prepared to take a punt on a successful result. He could have a cancer of high volume and high grade and still be suitable for this methodology. Radical prostatectomy without nerve sparing is ideal for a conservative patient of any age who has greater than 10 years life expectancy, poorer erections, is less concerned about his future potency and wants it out. He may have urinary obstruction and a higher grade, higher volume tumour. Conformal external beam radiotherapy is ideal for patients, or who are aged 70 and over, with health preconditions that make surgery inadvisable, or who are obese or averse to surgery, and who have a life expectancy of greater than 10 years. Brachytherapy with seeds is ideal for middle aged to older patients who have a fear of surgery and who are sexually potent and anxious to retain their sexual potency. They should have a low volume, low stage cancer in a small prostate, with no urinary obstruction. Obesity is not a problem for this therapy. High Dose Rate Brachytherapy is ideal for patients of any age without urinary obstruction, who prefer not to have surgery, or who have medical conditions that make surgery inadvisable. They may have an extensive tumour that is high volume and high stage, and they may be obese. Hormone Therapy is ideal for patients who have an incurable tumour (i.e. that has a high PSA and has spread beyond the prostate), or are over 70, or have other health problems that limit treatment options, or who have a life expectancy of less than 10 years. Note that hormone therapy is often administered as a pre-treatment to radiotherapy or brachytherapy with seeds. Active surveillance (or watchful waiting ) is ideal for a patient with a low grade, low stage tumour. It particularly suits older patients for whom retention of sexual potency is very important, who prefer natural therapies, or have a fear of surgery, or are prepared to take the risk, or gamble, that the tumour will not progress. MORE INFORMATION. It is very important to recognise that support is available through websites, books, support groups and second opinions.

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