Prostatepedia

Conversations With Prostate Cancer Experts


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Hypofractionated Radiation For Prostate

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Prostatepedia talks with Dr. W. Robert Lee, of Duke University Medical Center about hypofractionated radiation therapy. (Read the interview.)

Hypofractionation is a form of external radiation therapy that uses fewer, larger doses per fraction. Historically, the conventional radiation dose for most solid tumors is 1.8 to 2 Gray per day. (Gray is just the scientific term to measure the dose.) That conventional dose comes out of the French school of radiotherapy that dominated radiotherapy in the 1940s and 1950s and made its way over to the United States. Most patients treated with external radiation therapy for prostate cancer in 2016 are treated five days a week for eight or nine weeks.

 
There is some evidence that fewer, larger doses may, in fact, be better. Some studies have been designed to prove that hypofractionation is better, but the results of several studies have failed to demonstrate that theory. Other studies have been designed to determine if hypofractionation is “no worse than” conventional fractionation; these are known as noninferiority studies. Noninferiority studies are used to show that we can accomplish the same objective with a shorter, more convenient treatment.

 
I’ve just published a paper in the Journal of Clinical Oncology (April 2016) showing that you can accomplish the same thing with hypofractionation in five and a half weeks versus eight and a half weeks. There is another study from the United Kingdom, which was published in June 2016, which shows that you can accomplish the same thing in a four-week schedule that you can with an eight-and-a-half.week schedule. The results from all of these noninferiority studies are consistent: they show that you can accomplish the same objective in four or five weeks versus eight or nine weeks.

 
Another hypofractionation approach is stereotactic body radiation therapy (SBRT), which is an example of extreme hypofractionation. You get four to five treatments over a period of one to two weeks rather then four to five weeks. This is an emerging approach. We’ve been doing SBRT at Duke University since 2009 and I think it is safe, but it has yet to be compared to more traditional treatment in a rigorous manner. To repeat, we don’t have rigorous comparisons of SBRT to other definitive radiotherapy options, but they’re forthcoming.

Is a shorter course better for patients just for financial reasons, or is it also just more convenient?

Shorter courses are unambiguously more convenient for patients; in 25 years of practice I have never had a patient request longer courses of treatment.

Do patients usually travel to a radiation therapy center?

Yes. I tell men that, “We’re working on it, but we still haven’t figured out a way to bring the machine to you. You have to come to the machine.” There are significant economic advantages with shorter courses as well. In our current healthcare system, value is increasingly important. If you can accomplish the same thing with fewer resources, less time, and more patient convenience, then that is something you should do.


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Forms of Radiation Therapy

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Mack Roach III of the University of California, San Francisco talks with Prostatepedia about the pros and cons of different forms of radiation for prostate cancer.  (Download Prostatepedia’s August issue to read the interview.)

Different forms of radiation are typically used in different situations.

Localized radiation is used if you only have local disease. If you have low-risk, or favorable intermediate-risk disease, you don’t need to use hormone therapy with radiation therapy.

If you have T3 disease, we need to use external beam radiation with or without brachytherapy and hormonal therapy. We might want to treat the pelvic lymph nodes. We will definitely add hormone therapy.

 

From a practical standpoint, surgery is almost always the same. The only difference is that the surgeons might, for example, decide to do a lymph node dissection in a patient with more unfavorable features or we might decide to radiate a bigger area in patients with more unfavorable features.

 
The selection of which form of radiation to use also depends on the expertise of the doctor, how extensive the patient’s disease is, and patient consideration. For example, some patients are not good candidates for brachytherapy, because they’re not candidates for anesthesia or their prostate is too big or they have pubic arch interference. There are specific things that make us favor one treatment or the other.

 
The bottom line is that patient selection is part of the art of medicine.


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If Your Cancer Comes Back: Radiation

Dr. Michael Zelefsky of Memorial Sloan Kettering Cancer Center talks with Prostatepedia about using radiation therapy if a man’s prostate cancer comes back after treatment.  (Download Prostatepedia’s August issue to read the interview.)

 

After surgery, patients are generally followed. There is always a concern if we see

high-risk features after surgery that would put a patient at risk for the disease coming back. High-risk features could be positive margins or if the cancer breached the capsule or invaded the seminal vesicles.

We also ask if preventative radiation therapy, which is known as adjuvant radiation therapy, could be of benefit? Or would it be just as reasonable and logical to watch such patients? Should we treat a patient with radiation therapy if his PSA goes from zero to some level or he has a rising PSA level?

This is one of the most significant controversies in urologic oncology right now.
There are several important trials going on in the world that are trying address this very question. Is there a need for adjuvant radiation therapy? Or would early salvage radiation be acceptable? Can we delay the need to give these patients radiation? In general, when a patient’s PSA goes up after surgery, we consider radiation treatments to the prostate bed. That area could harbor microscopic cells. Frequently, patients who get radiation earlier, especially if they are at high risk for harboring microscopic cells in the prostate bed, can be successfully salvaged. Their PSAs could go down to zero once again. That is why close follow-up after surgery is necessary.
Of course there are many ongoing studies trying to figure out if hormonal therapy in the salvage radiotherapy setting could improve these results. Those studies are important. Hopefully, the results will become available in the near future. Radiation is also used in a recurrent setting when the disease comes back after radiation. The other option in that setting could be salvage prostatectomy, but many who do such salvage surgery procedures recognize that there is a risk of significant incontinence—from 25% to 50%.

More recently, we used seed implants to target the areas where the disease had come back based on careful imaging studies. For the last five years, we’ve been utilizing this so-called salvage brachytherapy in patients with what appears to be lower rates of incontinence. Results are comparable to what is achieved with salvage prostatectomy with lower risks of urinary incontinence.

 
Of course, there are other approaches such as salvage cryotherapy.
At Memorial Sloan Kettering, we are also treating patients in whom the disease has come back years later with salvage brachytherapy or salvage seeds. We tell patients that there is a risk of side effects when you add radiation on top of radiation. Fortunately, newer technologies to place seeds with image guidance and computer planning have significantly improved over the last number of years. This allows us to broaden radiation therapy options in the salvage setting.


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Using Hormonal Therapy With Radiation

Dr. Michael Zelefsky of Memorial Sloan Kettering Cancer Center talks with Prostatepedia about using androgen deprivation therapy alongside radiation therapy for prostate cancer (Download Prostatepedia’s August issue to read the interview.)

Is androgen deprivation therapy (ADT) used in combination with radiation therapy? Before, during, or after radiation therapy? Are there specific forms of ADT used?

Dr. Zelefsky: Many trials have been conducted over the last 20 and 30 years, which have demonstrated very clearly for more advanced high-risk tumors—especially patients with a Gleason 8 or higher or with a disease that has breached the capsule of the prostate—that utilizing hormones together with radiation has been associated with improved outcomes. A number of those studies demonstrated improved survival outcomes, as well. Using ADT with radiation therapy has become standard of care for patients with high-grade disease or aggressive-risk disease. In this country, ADT is very often given before the radiation starts for two or three months, continued during the radiation, and for a prolonged period of time after radiation.

Some studies, in particular one from Canada, suggested 18 months would be satisfactory for high-risk disease. A number of other studies used two or three years of hormonal therapy in conjunction with radiation treatment. It appears that these longer courses of hormonal therapy are associated with better results than shorter courses of six months or less for these high-risk patients.

It is unclear which is the optimal type of hormonal therapy. LHRH agonists such as Lupron (leuprolide) or Zoladex (goserelin), and more recently the LHRH antagonist Firmagon (degarelix), are used. Some studies have indicated that Firmagon (degarelix) may be associated with fewer cardiac-related side effects in the long run compared with other available hormonal therapy agents.

Fewer cardiac side effects in men who’ve had radiation therapy and taken the drug or just fewer cardiac side effects in any man who has taken the drug?

Dr. Zelefsky: In anybody taking the agent in general. There are other studies that have shown improved survival outcomes in patients with intermediate-risk disease.

Using hormonal therapy together with more standard radiation doses is associated with improved outcomes and, as I said, improved survival outcomes. When using external radiation therapy, a short course of hormonal therapy is now considered standard of care because of the two trials that demonstrate a benefit.

Of course, we counsel patients that there are side effects associated with hormonal therapy. ADT has an impact on a patient’s quality of life. But the potential benefit of improved outcome needs to be taken into consideration when using radiation. In the last several years, it has become standard to utilize hormones together with radiation—longer courses for high-risk disease, shorter courses of about six months for intermediate-risk disease.

Of course, a remaining question, which trials are now addressing, is whether hormonal therapy is needed when you use very intense radiation doses like seed implants combined with radiation. A radiation therapy oncology group study called the RTOG is currently looking at that very issue.

So they’re taking information we learned during the ASCENDE trial and adding ADT?

Dr. Zelefsky: Right. The ASCENDE trial asked whether the combined modality was better. But we have additional questions. Could you avoid hormonal therapy in such cases, or is it still necessary?


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Radiation Therapy: IMRT + SBRT

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Dr. Michael Zelefsky, a radiation oncologist, is Professor of Radiation Oncology, Chief of the Brachytherapy Service, and co-leader of the Genitourinary Disease Management Team at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia spoke with him about the pros and cons of radiation therapy versus surgery in terms of cancer control and side effects. (Download Prostatepedia’s August issue to read the interview.)

What are some of the forms of radiation therapy available to today for prostate cancer?

Dr. Zelefsky: One of the accurate ways of delivering standard external photon radiotherapy is IMRT, which stands for intensity-modulated radiation therapy. With the help of sophisticated computer programs, we can modulate and change the intensity of the radiation beam so it is much more targeted and more intense in the areas of the tumor. However, in the regions of the normal surrounding tissues, such as the bladder and the rectum, there is less intensity of the radiation given. Intensity-modulated radiation has become a standard approach in the delivery of radiation.

A newer form of IMRT is IGRT, or image-guided radiation therapy. In IGRT we use either markers or beacons placed within the prostate to pinpoint the prostate. The position can move from one day to the next and even during the actual radiation treatment itself.

By using imaging techniques to target the radiation beams, we can treat with less of a margin. That means we don’t need to include as much normal tissue in our focusing of the radiation beam. Ultimately, we observe fewer side effects with this approach.

We can also make real-time adjustments during the radiation beam to more accurately target the location of the prostate. We can then even further diminish those margins we use around our radiation beam and even more accurately pinpoint it. That is what has been done with SBRT, or stereotactic body radiation therapy.

SBRT delivers treatments at a higher dose at each session, condensing the typical radiation schedule from nine or 10 weeks to about seven to 11 days. We give a high dose of radiation at each session, but because the margins we utilize are even tighter and we are excluding more normal tissue, so far patients tolerate this higher dose. We nevertheless tell people that SBRT is a newer type of radiation treatment. It’s the same radiation beam that we used before, but the delivery is done in a shorter period of time with higher doses at each session.

SBRT has been used in a number of centers around the country for the last five to eight years. The results to date have been very good, indicating that tumor control rates look as good as those after prolonged sessions. People are tolerating these kinds of procedures well.

We don’t know yet whether it’ll actually be better than the nine to 10 weeks of treatment. We don’t have randomized trials to tell us definitively whether one is better than the other, but we are monitoring these patients very carefully to try to understand the success rate of these newer approaches.

For now, in my mind, SBRT represents an exciting development in the delivery of radiation for prostate cancer. It’s a convenient way of delivering treatment, and so far, very well tolerated.

Is the attraction of the abbreviated course of radiation offered by SBRT the convenience—i.e. it’s more efficient both for the medical center and for the patient? Or is there also an associated decrease in side effects because patients aren’t having as many sessions?

Dr. Zelefsky: Although there are fewer sessions, there is a higher dose at each session. Nevertheless, while there clearly is a convenience aspect that is a real advantage to many patients, there may be a biologic advantage associated with these higher doses condensed in shorter periods of time. It’s well recognized that, at least from a biologic perspective, those kinds of fractionation regimens, or delivery of treatment in condensed ways, may have a greater biologic potential for cancer cell kill. We haven’t seen long-term results yet demonstrating clear-cut differences, but I wouldn’t be surprised if those differences show up in the future.

We also have to be very cognizant about the fact that there are risks of long-term side effects that could be associated with SBRT. Patients need to be monitored very carefully not only for the short term, but also for the long term as well.


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Has your doctor registered?

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November 6-8, 2017. Dr. E. David Crawford, well-known urologist whose conversations we’ve featured in Prostatepedia, is hosting a meeting for urologists and primary care physicians at the Scottsdale Plaza Resort in Scottsdale, AZ.

Encourage your doctor to attend. The more up-to-date he or she is, the better he or she will manage your treatment.

 

 


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Radiation Versus Surgery For Prostate Cancer

Dr. Michael Zelefsky, a radiation oncologist, is Professor of Radiation Oncology, Chief of the Brachytherapy Service, and co-leader of the Genitourinary Disease Management Team at Memorial Sloan Kettering Cancer Center in New York City.

Prostatepedia spoke with him about the pros and cons of radiation therapy versus surgery in terms of cancer control and side effects. (Download Prostatepedia’s August issue to read the interview.)

 
Radiation therapy and surgery represent excellent treatment options and treatment interventions for prostate cancer. In general, when you look at the disease stage or aggressiveness level, it seems to provide equal outcomes for the treatment groups. I think there has been a significant change in thinking over the last five years in terms of the management of prostate cancer. Recommendations are based upon the initial risk group of the patient. A risk group is defined as the initial PSA level, the biopsy Gleason score, and the stage of the cancer based on rectal examinations.

 
More recently, we are provided with much more detailed information about the extent of the disease from MRIs and some of the new types of MRIs. This new technology has given us a much more detailed view of what is going on in the prostate.

 
Based on these risk groups, physicians now are better able to categorize and characterize the disease to make appropriate recommendations. Over the last number of years, I think especially at our institution, those patients who are known to have low-risk disease— that is those with PSA levels less than 10 and Gleason scores of 6 and below, without any significant volume of disease based on the biopsy— are recommended to undergo active surveillance. We encourage patients to go on active surveillance because their quality of life may be better in the long run than if they chose intervention for a disease considered biologically indolent and non-aggressive.

 
When it comes to men with intermediate-risk disease, or cancers with somewhat more aggressive features, then radiation and surgery are two really excellent options. Getting back to your particular question, those are the situations where patients have to make really complex and difficult decisions about treatment selection. I feel these decisions should be based more on their own preferences about quality of life. You can achieve similar results and cure rates with appropriate radiation dose levels, with hormonal therapy or without depending on the individual case, and these results are comparable to surgical outcomes.

 
Ultimately, a patient has to make a decision about what is better for him. There are clear advantages to radiation and advantages to surgery. For instance, there are lower risks in general for urinary incontinence with radiation-based approaches. There is really no major invasiveness associated with radiation-based procedures. It’s not a major operation. That may be very suitable for a patient who has underlying heart-related issues or other medical-related issues that could pose a challenge for the body to undergo a major procedure. Leaving those considerations aside, there are some people who prefer to avoid an operation and would rather go with less invasive approaches.

 
The disadvantages of radiation are that there is a higher chance for urinary bother or irritation symptoms, which translate into frequent urination or urgency. Some of those symptoms persist for a number of months, but they could persist even well beyond that and even require certain medications. Although the urinary control is excellent, there may be more frequent urination issues at night or during the day. There is also sometimes rectal bleeding or the like. Fortunately, with newer technologies and carefully-delivered radiation treatments, the likelihood of rectal, bladder, or bowel injury is nowadays less than 1%. Then, of course, there is sexual dysfunction. It appears that the risk or odds of sexual dysfunction after surgery or radiation is the same. Overall, there is about a 25% or 30% risk of loss of erection, which very often can be helped with medications like Viagra or Cialis. But this risk depends on many other factors, such as the baseline sexual function of the patient, age, and whether there are other medical issues present like heart disease or diabetes.

Are those side effects usually permanent?

 
Dr. Zelefsky: While immediately after surgery, there could be erectile dysfunction, which could improve, there is certainly a percentage of patients in whom improvements are not seen. They are left with erectile dysfunction. In my experience, the odds of having erectile dysfunction after surgery or radiation are pretty similar. I counsel patients that in both cases, either surgery or radiation, an individual needs to expect that there is a possibility of permanent loss of erections.
We’ve done some important studies in this area: in a randomized trial of 200 patients getting radiation, we gave some Viagra as a prophylactic to improve blood flow and others a placebo drug. The group who received the prophylactic Viagra (sildenafil) had better sexual function after two years compared to the group who did not have Viagra. This concept, known as penile rehabilitation, is well known among patients who undergo surgery. Many patients at Memorial Sloan Kettering who undergo surgery are advised to take medications like Viagra or Cialis (tadalafil) on a regular basis after the procedure.

Has there ever been any thought about taking Viagra before surgery or radiation?

 

Dr. Zelefsky: Given the way our study was conducted with radiation patients, we recommend that they initiate these medications before radiation begins, continue during radiation, and for at least six months to a year after radiation has completed. As far as the pros and cons of radiation versus surgery, I think overall in terms of cancer control, if the appropriate forms of radiation are given with great attention to the quality and accuracy of the therapy, the success rates will be similar.

 
There are different side effect profiles: more urinary incontinence with surgery compared to radiation, while on the other hand, radiation has more urinary bother symptoms. Sexual dysfunction is still an issue for both of these treatments. Fortunately, rectal side effects such as rectal bleeding have been significantly reduced in recent years, which we could attribute to more accurate delivery of the radiation beam.