Radiation Therapy as Prostate Cancer Treatment
By far, the two most common categories of treatment for localized prostate cancer (cancer that has not spread) are surgery and radiation therapy. There is an extensive amount of information on this site regarding surgery as an option, particularly robotic surgery which now accounts for approximately 95% of prostatectomy cases nationwide. So, if one is to choose surgery as the treatment that seems to make the most sense based on personality or in some cases the specific details of the case, all that is left to do is pick the surgeon. In the case of radiation therapy however, this choice can be very confusing to the patient as there are several options offered, and at times this can lead to an ill-informed decision influenced more by marketing than the specifics of the case or the appropriateness of the modality. Elsewhere on this site, one can find a history of surgery to treat prostate cancer and learn its evolution to robotic prostatectomy. Below you will find radiation therapy as a treatment for prostate cancer likewise discussed as a progression of technology so as to clarify why there are different options and where each may be best applied.
The concept behind radiation therapy is that radiation damages all cells but does so more readily to cancer cells than normal benign cells. Before the advent of PSA in the early 1990’s, and for several years after its introduction, radiation therapy was the most common treatment for localized prostate cancer. That radiation treatment was delivered largely as external beam radiotherapy, meaning the radiation is fired from outside of the patient as beams. What has always limited external beam radiation, or any radiation therapy for that matter, is the ability to deliver the highest radiation dose possible without causing undue damage to the nearby organs – the bladder and the rectum. The early technology of that time was problematic as the radiation beams were not well focused. This meant not only less available radiation dose to the prostate, but a lot of dose to the surrounding tissues. This inadequate dose led to the finding that external beam radiation given this way at that time did not eradicate prostate cancer very well which produced a very high and perhaps unacceptable recurrence rate. It is this situation that propelled open radical prostatectomy to instant popularity as a way to treat prostate cancer in the psa era. The abundance of radiation failures is also what caused the emergence of cryotherapy as the predominant secondary treatment after radiation failed.
External beam’s inferiority to surgery’s cure rate in the early 1990’s led to the development and popularization of radioactive seed implantation (brachytherapy) as what was felt to be a better way to deliver radiation. Here, approximately 100-150 small radioactive pellets are physically inserted into the prostate via needles using a special array and ultrasound in the operating room as a procedure under anesthesia. We call this “seeds”. By using pellets that emitted a type of radiation that did not stray far from each pellet, a higher dose of radiation could be given with the thought being that radiation to the bladder and rectum could be lessened. By the late 1990’s and early 2000’s, seed implantation was just as popular as surgery to treat prostate cancer as it was felt to be a way to get close to surgery in terms of cure rate with perhaps fewer side effects while undergoing a simpler procedure with a faster recovery time. Eventually, outcome data regarding seed implantation was gathered which evaluated its cure rate and effect on quality of life/side effects. The results were sobering. What was found is that seeds only came close to the cure rate of surgery in the Gleason 6 group but was strikingly inferior with all other Gleason scores. This result is still quoted today by many radiation therapists, but to understand the statement that brachytherapy has the same cure rate as surgery for Gleason 6 cases one must understand how the “seeds” data was gathered. This was a time when psa was not fully understood nor was early prostate cancer. In this era, most of the Gleason 6 cases were cases we would not treat today as we now understand that most low risk cases are best followed without formal treatment within an active surveillance program. Therefore, most surgeons feel that seeds would be shown to be far inferior to surgery in terms of cure even in the Gleason 6 group if studied today as now generally only higher risk Gleason 6 cases are offered treatment. But, the other eye-opening news came when quality of life was measured comparing seeds and open radical prostatectomy. What was found repeatedly was that many patients reported the side effects of seeds to affect their quality of life more negatively when compared to open surgery. From a urinary and fecal standpoint, seeds do not lead to a mandatory period of urinary incontinence as surgery does, but instead cause irritation that leads to frequent and urgent urination and bowel movements which can be even more annoying than urinary incontinence. Sexual function data showed that although brachytherapy does not tend to take away erections immediately following treatment as surgery does, radiation affects erections in a delayed fashion. Just as patients are hopefully recovering their erectile function at 9-12 months after surgery, radiated patients start to lose theirs due to the delayed effect of radiation on blood vessels. Studies therefore showed that when compared with surgery, radiation is the clear winner in terms of erections in the first year or two, but eventually the curves cross such that at two years and beyond surgery patients usually have better erectile function on average when having excellent erections prior to treatment. This pattern of erectile function after radiation is generally true for all types of radiation. All of these findings led to a steep drop-off in the utilization of prostate brachytherapy and created the need for a better radiation therapy option.
Meanwhile, technology rapidly progressed such that external beam radiation became far more focused with the development of techniques such as 3D Conformal IMRT. One form of focused radiation already existed called proton beam therapy, but this was offered in few locations such as Loma Linda University in California which led to limited data and few if any nationwide studies. Thus, with the advent of the widely available and utilized external beam based IMRT and similar more focused forms of radiation therapy, several sequential studies were performed with the hope of showing that now that external beam could offer higher radiation doses with less overlap to the bladder and rectum that cure rates would rival surgery with fewer side effects. Unfortunately, in most cases similar conclusions were reached suggesting that both IMRT alone or seeds alone do not offer cure rates that rival surgery, particularly in higher risk cases. What was concluded is that an extended course of external beam radiation therapy using more focused technology of approximately 7-8 weeks does provide adequate cure rates when compared to surgery in low to low/intermediate risk cases which is a conclusion that holds true today. More aggressive cases, and especially high-risk cases, required more research and thus more modification to the protocols to attempt to rival the cure rates of surgery.
The logical next step was to then offer combined protocols for higher risk patients such that external beam radiation, given in a shorter five or six-week course, and seed implantation would both be performed as a combined, sequential approach. This combined protocol did raise cure rates in higher risk cases, but now caused a side effect profile that most would say significantly exceeds that of surgery (again in different specific ways). The next change to be studied was to give hormone therapy during a more extended 10-week course of external beam radiotherapy before, during and after the radiation therapy as a “radiosensitizer” so as to increase cure rates. The theory here is that the administration of hormone therapy causes the cancer cells to be more unstable and expose their DNA more readily to the radiation. The hormone therapy is not given to treat the prostate cancer. The first major trial to establish and support this theory advocated six months of hormone therapy. The most contemporary study advocates 2 years of hormone therapy and cure rates are felt to be similar to surgery when this regimen is used. However, the use of hormone therapy tends to confound the data due to the well-known phenomenon that a large percentage of patients will not have their own testosterone production resume after two years of hormone therapy. This means that some patients in those studies are being treated permanently by hormone therapy which will mask the psa results. Today, the approach of 10 weeks of focused external beam radiation with between six months and two years of hormone therapy has largely supplanted combination radiation therapy as the most accepted regimen for higher risk patients. Cure rates are at least close to surgery, but now the patient must have added to the side effect profile of 10 weeks of radiation therapy the side effects of hormone therapy. The main side effect of hormone therapy when given for a limited period is bothersome hot flashes similar to what a woman may experience during the onset of menopause.
Proton Beam Therapy
Proton therapy is a form of external beam therapy that is now becoming more widely offered, and in essence is very similar to contemporary high quality IMRT. Proton therapy may become the modality to replace IMRT and similar focused approaches, and will clearly be the next focus of research trials seeking cure rates that hopefully rival surgery with fewer side effects. At this time, Dr. Engel considers proton beam and IMRT to both represent focused external beam approaches and he supports them both. Time will tell if proton therapy will require hormone therapy to deliver acceptable cure rates, a somewhat prohibitive aspect of using external beam today. Unfortunately, hormone therapy takes away the one clear advantage that radiation has over surgery in that erections are not affected in the first year or so after radiation therapy alone. Hormone therapy takes erections, and sexual desire, away. This seems to make surgery the clear winner long term in terms of erections to Dr. Engel, although both modalities will create a challenge for the patient with regards to erectile function.
Cyber Knife radiation is another form of focused external beam radiation that nearly every newly diagnosed prostate cancer patient will encounter on the internet and therefore must understand. Cyber Knife radiation is external beam radiation that is even more focused than IMRT and proton beam. This allows the total radiation dose to be given in five huge “fractions”, rather than many small ones over a long period of time. At first glance, it seems obvious that this should produce fewer side effects as less of the surrounding tissue gets radiated. Dr. Engel does agree that the usual side effects seen with radiation are lessened somewhat with this approach. Of course, patients find this extremely appealing as they should. All patients are generally looking for the treatment that offers the highest cure rate with the fewest side effects, and the marketing for Cyber Knife does make it seem very appealing in terms of side effects. It is given over only a 1 week span. However, too often the focus on cure rate is lost in the message. To date, there is little long-term cure rate data on Cyber Knife, and there is every theoretical reason to expect the cure rates to be inferior to those of radiation modalities that do have at least some overlap beyond the edges of the prostate. This overlap with IMRT and proton beam is what necessitates smaller fractions given over a longer time period. Today, if treatment is recommended to a patient, it is generally because his case is not low-risk and this causes the utility of Cyber Knife to be limited unless a patient is relatively low risk. Dr. Engel does support Cyber Knife, and often recommends it when the appropriate case is encountered. Such a patient is typically a patient who may have just a bit too much low grade cancer to only watch, or are older which may place less emphasis on the need for a very long term cure rate. In essence, Dr. Engel views Cyber Knife radiation to be an excellent replacement for seed implantation. The expectation is that it will not be found to be appropriate for higher risk cases, but is a viable alternative for lower risk cases with a reduction in side effects when compared to brachytherapy.
Ultimately, what this all means is that generally if a patient is contemplating radiation therapy for prostate cancer deemed anything but low risk, the most proven contemporary modality is external beam radiation as a long course coupled with a period of hormone therapy. Dr. Engel urges his patients to consider Cyber Knife only in certain circumstances of lower risk. When counseling patients, Dr. Engel explains that radiation and surgery are very different ways to approach a problem, and as long as the right modalities are considered in term of radiation usually the correct choice is the one that the patient feels matches his personality best. Surgery has an acuity to it. To some that is crucial, but to others that is terrifying. Surgery’s side effects of impotence and incontinence are immediate and then recovery begins. Radiation in general has immediate side effects (urinary and rectal urgency and frequency, <1% risk of incontinence, fatigue), but also has delayed effects such as its effects on erectile function described above, scarring to the urinary tract/strictures, painless rectal bleeding, bladder hemorrhage, and a small but definite risk of secondary malignancy. Surgery provides closure by providing an undetectable PSA whereas after radiation PSA drops slowly to a low point seen at one year which is maintained in the setting of cure. Many patients do not like how surgery is not a good second option after radiation whereas radiation can be and is performed when surgery fails. Dr. Engel counsels that a patient must “pick their poison” in that both radiation and surgery have poison, but different flavors. The patient must decide which of the modalities is the most tolerable.
All patients should understand all treatments, even the ones that may not be appropriate. Dr. Engel will always offer to send the patient to a radiation oncologist for a thorough discussion of the options, and will help in terms of providing names of surgeons he feels are excellent for a second opinion if desired. Ultimately, it cannot be stressed enough that choosing a treatment for prostate cancer is a journey that starts with education, a lot of it, and then eventually coming to a place where the patient can feel comfortable with the modality chosen and the doctor chosen to implement it. Dr. Engel will help in whatever manner the patient desires him to serve to reach this end.