The treatment of prostate cancer by external beam
radiotherapy14. My prostate cancer history.
(Updated 3rd July 2008)
.jpg)
The graph below shows my entire PSA history to date and the dates of critical parts of the treatment.
.JPG)
My first PSA measurement in May 2000 was 4.3 ng/ml and was instigated by an episode of blood in my urine (haematuria). I was then 64 years of age. A number of tests were carried out on kidney and bladder function but nothing untoward was found. Thereafter, I had further PSA measurements until it reached 6.3 ng/ml at the beginning of October 2001. I then had an 8 core biopsy that did not reveal any signs of cancer. My PSA continued to rise and, following another episode of haematuria, I had a series of PSA measurements close together to check if the the haematuria was causing rapid changes in PSA level. At this time, I also had a measurement of the ratio of free to total PSA which revealed a ratio of 12%. On the basis of this, I had another biopsy in which, gritting my teeth, 14 cores were taken. One of these showed a small focus of cancer with a Gleason grading of 3+3. Later, a second opinion on the Gleason grading was obtained from a US pathology laboratory and they graded it 3+4. Digital rectal examinations found nothing palpable so my t-staging was T1c. It was decision time. The available treatments at my local NHS hospital were either surgery or external beam radiotherapy. I finally rejected the idea of surgery on the grounds of the likely early side effects although I recognised that EBRT might produce side effects that were just as serious although later on after treatment. I think I preferred 'buy now pay later' as a strategy. I also decided to have a consultation at the Radiotherapy Clinics of Georgia (RCOG) where the treatment is permanent seed brachytherapy combined with external beam radiotherapy. RCOG report good disease free survival probabilities and use a more severe test of treatment 'success' in requiring the PSA to fall to 0.2 ng/ml or less. The success of this type of treatment regime is in accord with the results discussed in the 2nd review paper on web page 11 which shows that their combination of low dose rate brachytherapy and external beam radiation therapy gives a disease free survival probability that is significantly better than the standard ebrt treatment. Using the disease free survival probability calculator on web page 9 suggests that for a pre-treatment PSA of 10, the disease free survival probability with 120 Gy using Iodine 125 seeds plus a further EBRT of 45 Gy in 1.5 Gy fractions (which is the usual RCOG combination) is around 95% compared with 70% for EBRT alone of 70 Gy in 2 Gy fractions. On the other hand, when ebrt is combined with hormone therapy as discussed in web page 3, the differences become less. Moreover, there is some uncertainty about the level of side effects from brachytherapy combined with ebrt (Bradeis et al (2000)) although this is something that seems generally to be played down by RCOG enthusiasts. The treatment would also have been expensive and so, with some misgivings, I decided against the RCOG option.
My final choice was to go with the 'standard' 70 Gy of 3-D conformal external beam radiotherapy supplemented with hormone therapy in the form of 150mg daily of the anti-androgen Casodex taken 3 months before the start of radiotherapy and to be continued for possibly five years after the radiotherapy. I have to admit also that there was at the back of my mind the idea that provided the treatment was sufficiently effective to keep me alive for 5 years or more, there might be better alternative treatments then available. In short, I decided to play a form of Russian roulette! When I started taking the Casodex, my PSA had risen to just over 10 ng/ml. With a Gleason score of either 3+3 or 3+4 depending on the pathology laboratory and a t-staging of T1c, I would have been described as an intermediate risk patient. According to the Partin tables, there was a 49% probability of the disease being organ confined, a 40% probability that there was some extra-capsular penetration, an 8% chance of seminal vesicle involvement and a 3% chance of lymph node involvement. Additionally, a bone and CT scan did not show any signs of metastasis. This all seemed to add up to a case that was suitable for external beam radiotherapy with a probability of remaining disease free of around 70%.
After three months of Casodex just prior to the start of radiotherapy, my PSA had fallen to 2.5 ng/ml. I then had a final CT scan to enable the radiotherapy planning to go ahead. The consultant discussed with me the planning chart explaining that he was going to extend the margin of treatment to around 10mm outside of the prostate gland but that the seminal vesicles would not be targeted. He also mentioned that only about a third of my rectum would be in the high intensity field in the neighbourhood of the prostate and he did not think this would cause any problems. I am happy to say that he was correct in this and, in view of the Partin table results, the decision to leave out the seminal vesicles also seemed reasonable. He also offered me the option of a single dose of electron radiotherapy to my breasts to counter breast enlargement (gynaecomastia) caused by taking the Casodex. I accepted this option and subsequently I experienced no enlargement problems although I did experience breast tenderness. As an alternative to radiotherapy, it is also possible to take tamoxifen which seems even more effective at preventing both breast enlargement and breast pain - see Perdona et al (2005) and Saltzstein et al (2005).
Apart from some stinging and weak flow when urinating, I did not experience any side effects from the radiation treatment. By week six, I continued to feel fine and so I approached the oncology consultant about the possibility of increasing the overall radiation dose on the basis of the results shown on web page 4 of this site. I am not sure what reaction I expected to my 'lay' suggestion but he was sympathetic to the idea and agreed to a further two radiation fractions bringing the total dose to 74 Gy. This may seem a small addition but it would have improved the disease free survival probability by another 5% to 10%.
Two months after the end of radiotherapy, my PSA had fallen to 0.4 ng/ml and then it dropped below the 0.1 ng/ml level which was at the limit of the assay accuracy. Effectively, my PSA was zero. This all seemed very good. Nevertheless, just over a year after the end of radiotherapy, I became aware of the D'Amico trial results discussed in web page 3 and I considered the possibility of stopping taking the Casodex. This was also influenced by the fact that the large Casodex trial (See and colleagues (2002)) showed a slight increase in mortality in the Casodex arm of the trial among the low risk patients and its use in such cases was no longer recommended. Also, although the side effects from Casodex were not particularly odious, its use was not something I enjoyed. I discussed the matter with the consultant who reassured me that it was not an unreasonable course of action in view of the emerging data - although it was not necessarily a straightforward decision either. I stopped taking the Casodex in September 2004 - just over a year after the end of radiotherapy.
Three months after stopping the Casodex, my PSA recovered to 0.7 ng/ml. but, over two years, my PSA climbed gradually to a maximum value of 2.0 ng/ml (see the graph below). In previous versions of this web page, I concluded that my treatment had failed but, over the last two years, my PSA readings have remained relatively stable at between 1.6 and 2.0 ng/ml. Almost five years after the radiotherapy treatment, it is not exactly obvious what is happening but it is no longer clear that the treatment has failed. For now, I am feeling fine although, at the end of 2007, I had an episode of epididymitis - an infection of a testicle - which was quite painful and also unresponsive to a range of antibiotics. However, it finally cleared up on its own.
The episodes of haematuria (which occurred about once a year) have been absent now for nearly four years and the only episode after radiotherapy was very slight compared to the pre-treatment haematuria. Whatever caused the haematuria seems to have been 'destroyed'.
.JPG)
REFERENCES.
See W.A., Wirth M.p., McLeod D.G. et al (2002).
Bicalutamide as immediate therapy either alone or as an adjuvant to standard care of patients with localised or locally advanced prostate cancer: first analysis of the early prostate cancer program.
J. of Urology, Vol. 168, pp.429-435.
Brandeis, J.M.,Litwin, M.S.,Burnison, C.M. and Reiter, R.E. (2000)
Quality of life outcomes after brachytherapy for early stage prostate cancer.
J.of Urology, Vol.163, pp.851-857.
Perdona S., Autorino R., De Placido S. et al (2005).
Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial.
The Lancet Oncology, Vol.6 No. 5, pp.295-300.
Saltzstein D., Sieber P., Morris T. & Gallo J. (2005)
Prevention and management of bicalutamide-induced gynecomastia and breast pain: randomized endocrinologic and clinical studies with tamoxifen and anastrozole
Prostate Cancer and Prostatic Diseases Vol. 8, pp. 75-83
IS THERE ANYTHING I WOULD HAVE DONE DIFFERENTLY?
Even with the benefits of hindsight, there are only a few things that I would have changed within the framework of the options open to me at the time. When I had my first biopsy, I had not appreciated how low the possibility of finding a smallish volume of cancerous cells can be. It was only after this point that I did the analysis contained in the review 3 in web page 12. If I had appreciated this, I would have gritted my teeth on this first occasion and suffered the fourteen samples that I managed on the second biopsy. It is still possible that the cancer would have been missed but the probability of hitting the target would have increased by about a third. If the prostate cancer had been found in the first biopsy, the treatment outlook would have been somewhat better with a PSA of 7 ng/ml rather than the final pre-treatment PSA of 10 ng/ml.
Secondly, I should perhaps have argued for an even larger overall dose than the 74 Gy I received - say, 76 or 78 Gys of radiation. However, this is from the standpoint of not having suffered any late side effects. With 3-D conformal radiotherapy, it is quite possible that the consultant would have considered this a few Grays too far to risk.
It now also looks as if Casodex is not as effective as Zoladex when used in conjunction with external beam radiotherapy (web page 3). Since it also seems that the benefits of Zoladex can be achieved by as little as six months of its use, I would now have preferred to accept the more unpleasant side effects from a six month course of Zoladex rather than the use of Casodex.
At the time of my treatment, the only options I had were surgery or external beam radiotherapy and I have no regrets about choosing radiotherapy. However, since then, both low and high dose rate brachytherapy have become locally available under the NHS and I would probably choose high dose rate brachytherapy now. As discussed on web page 5, there is an opportunity with high dose rates to exploit the different radiosensitivity of prostate cells to the cells of the surrounding organs - primarily the rectum. This possibility exists for both external beam radiotherapy and high dose rate brachytherapy but not for low dose rate brachyhterapy where the majority of DNA fatal lesions occur from single photon passes - see Review 2. The optimal dose and dose fractions have almost certainly not yet been achieved but it is perhaps the most promising area for development in radiotherapy in increasing the therapeutic impact of the treatment without increasing adverse side-effects.
For anyone who has had low dose rate brachytherapy with permanent seeds, it should be said that this form of treatment seems somewhat better than external beam radiotherapy for patients at a low or intermediate level of risk. However, the pros and cons of the various treatment options are fairly subtle and as both our understanding of radiobiology and the technology of dose delivery evolve, the balance between these pros and cons shifts too.
If anyone wants to know anything more about my treatment experiences, please contact me on
