RINECKER PROTON THERAPY CENTER STATUS REPORT: TENTH MONTH OF CLINICAL OPERATION, JANUARY ‘10
TREATMENT OPTIONS FOR PROSTATE CANCER – A DECISION-MAKING AID FOR PATIENTS – AND A POSITION STATEMENT BY THE RPTC
It was not just in specialist journals but also in one of the two most established science magazines in the world – the American Science (November 29, 2008 A User´s Guide to Cancer Treatment) – that a statistical study was recently published detailing how prostate cancer is treated in the USA. The object of this study was to determine the frequency of "expectant therapy" (i.e. doing nothing), hormonal (antiandrogenic) therapy, operation (radical prostatectomy) and irradiation (with various techniques, see below). The result was that these four options were applied regionally with highly varying frequency in the individual states of the USA. These differences are not in any way explainable through racial differences in the patient population (which in any case do not have any medical significance). There remains the startling conclusion that the procedures used on each individual patient were not necessarily based on the available clinical evidence or the state-of-the-art but on other aspects instead. What happens with the patient depends on where he goes for therapy and who he meets there.
All these therapy methods in various ways tip the inevitable scales between therapy success and side effects. For that reason alone the patient should participate in the decision as to which method will be applied to him. Here at RPTC we use proton scanning for the treatment of prostate carcinomas. It is the purpose of this overview to explain to patients the logic of this position.
It is not possible to cite the references – which are estimated to number over 300 – within the scope of this overview. We therefore refer
- to the previous Monthly Reports regarding the performance of the RPTC facility
- to the publications of the Loma Linda Clinic regarding the success rates of proton Therapy
- to an overview regarding the dosage determination for prostate carcinoma (in publication) including references
- to the aforementioned Science article regarding the therapy methods for prostate carcinomas
all of which you can click on.
Prostate carcinoma is the most common form of cancer found in men (see Fig. 1). Unlike with the second most common cancer in men, i.e. lung carcinoma, there are no self-inflicted risk factors with prostate cancer. Contrary to the latest publications in the daily press about relatively young twin brothers who both developed prostate carcinomas, there are, according to current evidence, few significant hereditary factors (gene constellations). The occurrence is a largely random event; the peak age for the clinical appearance of a prostate carcinoma is 71 years old. However, a new Swedish Puplication has found an elevated prostate cancer mortality for sons and brothers.
The cited figure also shows that men die less frequently as a result of prostate carcinomas than from other types of cancer such as lung carcinomas or the carcinoma most frequently found in women, i.e. breast cancer. This comparably good chance of survival is due to three factors, the individual weighting of each being difficult to quantify: 1. A relatively successful early diagnosis and a relatively successful treatment method. 2. Slow growth compared to other forms of cancer and 3. a peculiarity of this form of cancer - no fewer than 80% of men over the age of 70 exhibit on the occasion of a microscopic examination (e.g. during autopsy) of the prostatic tissue cells, which according to all oncological terminology, are classifiable as malignant cancer cells (so-called latent prostate carcinoma). These cells generally divide so rarely, however, that there is no local spreading or metastasis – the patient does not live to experience the cancerous outbreak. It was not least this apparently benign nature of prostate cancer that made it possible to have quite differing treatment plans.
Dispensing with therapy measures – doing nothing.
It is not possible to use microscopic tissue examinations to reliably determine when such an “inactive” cancer becomes active. So there are no definitive parameters to determine when therapeutic inactivity is justifiable. Refraining from taking action is a question of judgment for the therapist which is made all the more difficult primarily because the risk of operation has significantly decreased in the last decade with the physical strain of the patient even approaching zero in the case of proton scanning.
Hormone treatment and chemotherapy.
With hormone treatment substances are applied to block the male hormones (antiandrogenic therapy), because prostate carcinoma cells frequently (if not always) will still react to natural hormonal regulation. In this therapy, as with equally relevant chemotherapy, not all of the carcinoma cells will necessary die off. As with all drug-based therapies, solid tumors usually form resistant surviving cells. Both forms of therapy are usually not able to eliminate prostate cancer by themselves; chemotherapy alone will, for example, only increase the survival time by a mere 2.5 months. They are therefore only applied in addition (adjuvant) to other therapy methods such as surgery or irradiation, particularly in relation to widely spread forms of cancer or in the event of relapse (recurrence).
Surgical procedures are effective, they have been used in every stage of prostate carcinoma. However, where the cancer has spread throughout the local area (lymph node involvement), external irradiation of areas that are no longer technically accessible for a complete (radical) operation (RO resection) is imperative. In those cases, the surgical procedure forms part of a combination therapy.
The problem with the operation (operative mortality rate < 1 %), which by necessity removes the entire prostate including its healthy parts along with a piece of the urethra and the adjacent nerve plexus (radical prostatectomy), are the side effects - incontinence (3-5 %) and impotence (50 - 80 %). The high probability of stress incontinence (urinary incontinence that especially occurs when the body is under physical strain) and the overwhelming probability of the sudden occurrence of impotence (erectile dysfunction), which cannot be reliably managed with sildenafil (Viagra and such like), requires every reputable treatment provider to take account of the patient's intentions when drawing up therapy proposals and to recommend similarly effective (see below) non-surgical therapeutic procedures. These considerations are given all the more weight since an argument made by radiotherapists who are critical of surgical procedures cannot be denied: the surgical procedure is ineffective with a proportion of operated patients because these patients unfortunately already have metastases. And with another group (see above) the efficacy of the surgical procedure is in any case pointless because the patient would not have experienced the consequences of his slowly growing prostate cancer. Critics maintain that only in a fraction of operations do prostatectomies afford a gain in life expectancy that can be justified given the inherent side effects.
Different radiation techniques.
The dosage analysis mentioned above sets out in detail how, from the therapeutic efficacy perspective, the killing off of cancer cells with modern radiation methods is now on a par with surgical prostatectomy for all stages of prostate carcinoma. The reliability of the cancer treatment is identical. But the radiation methods do not give rise to the surgical risks of possible incontinence and sudden impotence that is no longer correctable.
The second important assertion contained in this report is based on the evidence that the reliability of the treatment, the rate of recovery is dependent on the applied radiation dosage; on the therapy dose in the tumor. But the prostate is closely surrounded by organs sensitive to radiation, i.e. the bladder and the rectum, the front wall of which is located directly against the prostate and will also be included in the path of the radiation. These organs often react with hemorrhage, which is no longer of a temporary nature only, once the dosage becomes too high. The hip joints are situated at a distance from the external radiation entry points. Even without additional damage these are quite often worn out given today's life expectancy meaning that artificial replacements will be required. The same applies to the large blood vessels in the groin area, the arteries of which are prone to arteriosclerotic occlusion processes, which are frequently the target of vascular surgical interventions even without any radiation damage. It is not the limited performance of X-ray devices (linear accelerator, IMRT, Cyberknife, tomotherapy, Rapid Arc), but the collateral damage caused by these methods, known as X-ray therapy or photon therapy (not to be confused with protons), which gives rise to the undesirable limitation of the efficacy of the tumor dosage when using x-ray radiation. The natural dosage distribution of X-ray radiation within the body leads to the geometrically-dependent and unavoidable damaging of healthy surrounding tissue with three to five times the total dosage compared to analog proton dose.
The solution that appeared capable of canceling this X-ray therapy dosage limitation was the implantation of the prostate from the intestinal region outwards with radioactive, isotope-loaded needles (seeds) - known as brachytherapy (or internal interstitial radiation). This short-range radiation sources, of which up to a dozen are inserted into the prostate by X-ray and ultrasonic control, and initially create an optimum dosage centered on the tumor in the prostate – provided the needles can be positioned as precisely as required under the dosage plan. According to the majority opinion these implantations must be applied several times, but the changes made to the tissue of the prostate during the first irradiation render the second implantation imprecise and a third is usually regarded as impossible in practice. Moreover, it is not possible to access more distant tumor spreads (lymph nodes) with the limited radiation range; it is therefore always necessary to combine brachytherapy with external radiation. While it has been possible to prove the positive healing effects that brachytherapy has in combination with external radiation, e.g. X-rays, due to its doubled complexity it remains a treatment method that is not without its problems and side effects.
Proton scanning optimally concentrates the radiation dosage into the target area, i.e. the tumor. With the same tumor dosage the contamination of healthy area is reduced to one third to one fifth (see previous monthly reports and figure 2), which widens the limits to which the tumor dosage is otherwise subject. Proton scanning consequently enables the beneficial dosage distribution of combined brachytherapy/X-ray radiation to be achieved with a single treatment.
Already the not completely perfected older proton radiation method employing the scattering system (in which the high tumor dosage also occurs in the entry area of the radiation) was able to achieve convincing results at the first proton clinic of its type anywhere in the world in Loma Linda near Los Angeles, with 90 % ten-year survival for the early stages of the illness (literature), as was recently demonstrated anew at the last proton expert congress in October 2009 in Heidelberg.
Reduction of duration of therapy: hypofractionation.
X-ray radiation, an electro-magnetic beam, loses its effect in a declining exponential curve the deeper its goes into the body, meaning that it is most effective at skin-level becoming much weaker at the point of the deeper lying tumor, the irradiation, however, continues to shoot through the entire body with decreasing power. In contrast, particle radiation methods, such as proton scanning that do not employ electromagnetic waves but atomic nuclei instead, which are shot at high speeds into the body, have the advantage that the penetrative and therefore effective depth of this ionizing radiation can be adjusted as required by the operator and therefore applied with maximum effect into the tumor. There is no "shoot through" effect. Furthermore, it achieves its most potent force not upon entry into the body but at the end of its trajectory in the tumor. This method is optimized in proton scanning, where (with larger tumors) up to 10,000 single points are irradiated individually point by point on a dosage-controlled basis with an overlapping effect.
The older proton scattering method does not quite achieve this optimum level. It produces a characteristic tumor dosage excess at the front wall of the tumor (in the direction of the radiation source). Other experimental forms of ion therapy, such as the heavy ion process as introduced in Heidelberg, result in excess toxicity outside of the tumor, e.g. behind the tumor, the clinical effect of which remains to be assessed.
These particle radiation methods have one significant thing in common however - they not only kill the tumor but preserve the healthy tissue as well. Apart from the concentration of the pure dosage in the tumor this also has another benefit - prostate carcinomas are irradiated with X-rays up to 41 times on 41 days. This is done in the expectation that the jointly exposed healthy tissue will recover slightly more quickly from the radiation than will the tumor. These differences in recovery (repair capacity) are recorded in mathematical models, whereby at least the bandwidth of these models is clinically assured. So if the healthy tissue is exposed less, fewer radiation sessions are required – the RPTC applies radiation in just 21 sessions. This advance achieved by the RPTC not only brings relief to patients, the specified mathematical models demonstrate clearly that the concentration of the radiation not just locally but also in time with fewer sessions causes more damage to the tumor (hypofractionation).
The future of proton scanning.
The objectives are clear – a highly effective, lethal tumor dosage with the lowest possible damaging dosages and side effects to healthy tissue with retention of continence and potency.
The RPTC does not conduct any experimental therapies. From the American institutes, which have a head start, positive, generally accepted study results relating to prostate proton therapies emerge, and become thus available to us to utilize for health care. Therefore, the future optimization of RPTC proton scanning, which is already superior is clear:
- To date, as expected, we have not observed any permanent damage to the intestinal mucosa of the rectum with the dosages we have selected. Most recently more and more experience has been gathered using a method in which absorbable (metabolizable) collagens are injected between the prostate and the rectum. This creates a spatial separation of these two organs thereby making it easier to achieve higher dosages in the prostate with no side effects.
- Several publications containing reductions of the number of sessions (hypofractionation) report positive results. It can be envisaged that RPTC will also be able to lower the number of individual sessions and therapy days down to less than 20.
- This current good tolerance already recorded at older proton scattering facilities such as Loma Linda, as well as the recent experiences of the RPTC, reinforce the tendency towards the increase of the physical dosage in the tumor, at least in more advanced tumor stages, with a further foreseeable increase of the chances of recovery.
Summary and recommendations specifically from the perspective of the RPTC.
- Because modern radiation therapy has the same efficacy as a surgical procedure, but both the operative risk itself and the consequential risks of incontinence and impotence are largely avoided, we recommend that modern radiation therapy be applied to cure to all tumor stages of prostate carcinoma
- In applying radiation therapy the highest possible tumor dosage should be aimed for so as to improve the chances of recovery.
- The administrable tumor dosage of X-rays is limited because of side effects. These are indisputably lower in the case of proton therapy.
- In our opinion, the optimum dosage concentration in the tumor using proton scanning makes it the medical method of choice for patients with a prostate carcinoma.
- In the case of combination therapies using localized methods and external radiation, a combination employing proton scanning is preferable. This applies for example to patients who have to undergo a urological surgical procedure because they are already exhibiting urinary tract displacement.
EXPANSION OF OUR TEAM
With the beginning of operation of the third treatment unit (image) (gantry three of four) at the start of March 2010 along with the fourth and final gantry at the start of July 2010, we are looking for further dedicated staff to help us achieve full-scale operations. Find out more here.
FILM - HIGH-PRECISION TUMOR IRRADIATION WITH PROTONS
The following film will give you an idea of how the therapy works. Film