PROSTATE CANCER TREATMENT IN GERMANY

Radical prostatectomy is the most widely used treatment for prostate cancer. It is successful in the locally confined form of the cancer. As prostate cancer progresses, the chances of completely removing the cancerous tissue, and thus the chances of cure, decrease. Radical removal of the prostate  is often considered only in those cases where life expectancy is at least 10 years. Radical prostatectomy means removal of the prostate together with its capsule, the seminal vesicles and the vasa deferentia. Minimally invasive surgery is not possible in locally advanced prostate cancer.

Laparoscopic radical prostatectomy is a minimally invasive surgical method, so-called keyhole surgery, which is becoming increasingly widespread. Only a few small incisions (punctures) are made in the abdominal wall, through which an endoscope and surgical instruments are introduced. This method is used for uncomplicated tumour removal.

If the size of the tumour allows, laparoscopic prostatectomy can be performed with the use of robotic technology (the da Vinci robot). Robot-assisted prostatectomy makes it possible to avoid the most serious consequence of radical prostatectomy – erectile dysfunction,

Advanced stages of prostate cancer are treated with a combination of radiotherapy, hormone therapy and chemotherapy. New effective drugs have recently appeared for the most severe forms of prostate adenocarcinoma, including those with the development of metastases.

If the tumour has spread beyond the prostate, cure is unlikely to be possible; systemic treatment is aimed at reducing the size of the tumour or limiting its spread.

For patients with a locally advanced tumour or with metastases, an effective option may be androgen deprivation by castration, either surgical, by means of bilateral orchiectomy, or medical, by means of LHRH agonists such as leuprolide, goserelin, triptorelin, histrelin and buserelin, with or without radiotherapy. LHRH antagonists (for example, degarelix) can also lower the level of testosterone, as a rule faster than LHRH agonists. LHRH agonists and antagonists generally reduce the serum level of testosterone by almost as much as bilateral orchiectomy. All antiandrogen treatments lead to loss of libido, erectile dysfunction and sometimes hot flushes. LHRH agonists may cause a temporary rise in the PSA level. Some patients may benefit from adding antiandrogens to the treatment (for example, flutamide, bicalutamide, nilutamide, cyproterone acetate [the latter is not marketed in the USA]) in order to achieve complete androgen blockade. Combined androgen blockade usually involves prescribing LHRH agonists together with antiandrogens, but its benefit appears to be only minimally greater than that of treatment with an LHRH agonist (or degarelix, or orchiectomy) alone. Another approach is intermittent androgen blockade, aimed at delaying the development of castration-resistant prostate cancer and helping to minimise some of the unwanted effects of antiandrogen therapy. Complete androgen deprivation is given until the PSA level falls (usually to undetectable values) and is then stopped. Treatment is started again when the PSA level rises above a certain threshold, although the ideal threshold value is still not defined. The optimal timing of administration and of the treatment break has not been established and varies considerably in the practice of different doctors. Androgen deprivation can substantially impair quality of life (for example, self-esteem, attitude towards the cancer, general vitality) and cause osteoporosis, anaemia and loss of muscle mass when the drug is given long term. Exogenous oestrogens are rarely used, as their administration is associated with a risk of cardiovascular and thromboembolic complications.

Hormone therapy is effective in the presence of metastatic prostate cancer for a limited period of time. Cancer that progresses (as shown by a rise in the PSA level) despite a testosterone level (< 50 ng/dl) resulting from castration is classified as castration-resistant prostate cancer. Treatment methods that increase survival in castration-resistant prostate cancer (many of them known since 2010) include the administration of docetaxel (a chemotherapy drug from the taxane group), sipuleucel-T (a vaccine developed to stimulate the immune system against prostate cancer cells), abiraterone (blocks androgen synthesis both in the tumour and in the testes and adrenal glands), enzalutamide (blocks the binding of androgens to their receptors) and cabazitaxel (a chemotherapy drug from the taxane group that can act on tumours which have become resistant to docetaxel). Data from some studies suggest that sipuleucel-T should be used in the early stages of castration-resistant prostate cancer. However, the choice of method may involve many factors, and data from some studies may be useful for predicting outcomes; it is therefore advisable to devote attention to educational discussions with the patient, so that decisions can be taken jointly.

Osteoclast inhibitors (for example, denosumab, zoledronic acid) can be used as adjuncts for the treatment and prevention of complications associated with bone metastases (for example, pathological fractures, pain, spinal cord compression). Conventional external beam radiotherapy is used to treat individual bone metastases. It has recently been established that radium-223, an alpha emitter, prolongs survival and also prevents complications caused by bone metastases in men with castration-resistant prostate cancer.

Local treatment is aimed at curing prostate cancer and can therefore also be classed as radical therapy. Radical prostatectomy, certain forms of radiotherapy and cryotherapy are also used as treatment methods. Careful counselling about the risks and benefits of these treatment methods, taking into account the individual characteristics of the patient (age, state of health, features of the tumour), is of decisive importance in the decision-making process.

Radical prostatectomy (removal of the prostate together with the seminal vesicles and regional lymph nodes) is the best option for patients under the age of 70 with a localised tumour. Prostatectomy is also suitable for some elderly men, depending on age, comorbidities and the ability to tolerate surgery and anaesthesia. Prostatectomy is performed through an incision in the lower abdomen. A robot-assisted laparoscopic approach has recently been developed which minimises blood loss and hospital stay, but does not change morbidity or mortality. Complications include urinary incontinence (in about 5–10% of patients), bladder neck sclerosis or urethral stricture (in 7–20%), erectile dysfunction (in 30–100%, which depends strongly on age and on preoperative function) and rectal injury (in 1–2%). Nerve-sparing radical prostatectomy reduces the likelihood of erectile dysfunction, but it cannot always be performed; this depends on the stage and location of the tumour.

Cryotherapy (destruction of tumour cells by freezing through cryoprobes with subsequent thawing) is a less common technique, and its long-term results are not yet known. Side effects of the treatment include bladder outlet obstruction, urinary incontinence, erectile dysfunction, rectal injury and pain in the rectal area. Cryotherapy is usually not the primary method of choice, but it may be used if radiotherapy does not produce the expected results.

Conventional external beam radiotherapy usually consists of exposing the gland to radiation at a dose of 70 Gy over 7 weeks, but this technique has been superseded by 3D conformal radiotherapy and intensity-modulated radiotherapy (IMRT), in which doses of up to 80 Gy are safely directed at the prostate; the data show that the rate of local control is higher, especially for high-risk patients. Some reduction in erectile function is seen in about 40% of patients. Other side effects include radiation proctitis, cystitis, diarrhoea, fatigue and possibly urethral strictures, especially in patients with a history of transurethral resection of the prostate. The results of radiotherapy and prostatectomy may be comparable, particularly in patients with a low PSA level before the start of treatment. Newer forms of radiotherapy, such as the use of proton therapy, are more expensive, and the benefits of these methods for a man with prostate cancer have still not been established. External beam radiotherapy also has a role in cases where cancer remains after radical prostatectomy, or if the PSA level begins to rise after surgical treatment in the absence of metastases.

Brachytherapy consists of implanting radioactive seeds into the prostate through the perineum. These seeds emit a burst of radiation over a limited period of time (usually 3–6 months) and then become inert. Clinical trial protocols are currently determining whether implantation of high-quality seeds as monotherapy, or implantation combined with external beam radiotherapy, is preferable for intermediate-risk patients. Brachytherapy also leads to a decline in erectile function, although this may be delayed, and patients may respond better to treatment with phosphodiesterase-5 inhibitors than patients whose neurovascular bundles were resected or injured during surgery. Increased urinary frequency and urgency and, less often, urinary retention  are common side effects, but they usually resolve over time. Other side effects may include increased bowel motility, false urges to defecate, bleeding or ulceration of the rectum and rectoprostatic fistulas.

If a cancer confined to the prostate is high-risk, different treatment methods can be combined (for example, high-risk prostate cancer should be treated with external beam radiotherapy in combination with hormone therapy).