You are here: Home: PCU 1 | 2006: Richard G Stock, MD

Tracks 1-13

Track 1 Introduction Track 2 Long-term follow-up of brachytherapy Track 3 Long-term outcomes of brachytherapy, external beam irradiation and hormonal therapy for patients with higher-risk disease Track 4 Genetic susceptibility to radiation therapy Track 5 Treatment of high-risk disease with long-term hormonal therapy Track 6 Clinical use of postprostatectomy radiation therapy Track 7 Evaluation of PSA after radiation therapy Track 8 Reduction of urinary side effects with the real-time intraoperative brachytherapy technique Track 9 Number of brachytherapy implants performed to acquire proficiency Track 10 Therapeutic approach to patients with PSA progression Track 11 Future directions in the delivery of radiation therapy Track 12 Selection of patients for watchful waiting Track 13 Impact of therapies to optimize local control and patterns of disease failure

Select Excerpts from the Interview

Track 2

DR LOVE: Can you briefly provide an overview of the work you and your colleagues have done on the use of brachytherapy?

DR STOCK: We started treating patients with prostate brachytherapy in 1990, so now we have 15 or 16 years of data. We’ve put a lot of effort into following up on patients to see how they’ve done over time.

Our data set has matured and now shows us that the earlier outcomes we observed with our patients have held up.

One of the things we’ve seen with longer follow-up is that many of the early and late side effects of radiation that usually occur within the first five years of therapy are not more severe or different over time (Stone 2002). This finding was based on following our patients and asking them questions regarding their urinary function, continence rates and potency preservation. We found the side effects patients were experiencing after five years held up over time, with no new side effects developing.

For example, we found that preservation of sexual function was maintained. This supported our earlier publications on potency preservation, in which we reported that approximately 60 percent of patients that were potent prior to brachytherapy maintained some form of potency after treatment (Stock 2001).

An interesting outcome we are finding with longer follow-up is that younger patients in particular are doing extremely well after treatment, with preservation of potency in the range of about 90 percent. This means that patients in the long term are doing well with brachytherapy as a treatment for prostate cancer.

We’re finding similar results with the cancer control rate over time. We have determined that many of the patients who fail treatment in terms of biochemical recurrence do so within the first five years.

At longer follow-up, very few new or late recurrences of the cancer have been reported. Our results show a 90 to 95 percent biochemical control rate out to about 10 years (Kollmeier 2003; Stock 2006a; Stone 2005).

We don’t have a data set to compare these brachytherapy outcomes with radical prostatectomy or external beam radiation therapy, but these outcomes seem to compare nicely to those reported by the major cancer centers.

Track 3

DR LOVE: How do you approach patients with intermediate- or high-risk disease?

DR STOCK: We’ve always attempted to customize therapy, using different treatment approaches for different stages of disease.

For patients with low-risk disease, we primarily use an implant alone. For intermediate-risk disease, we usually use an implant combined with external beam radiation therapy or an implant combined with neoadjuvant or adjuvant hormonal therapy.

For our patients with high-risk disease, we use a combined approach that involves hormonal therapy, implant and external beam radiation therapy. Our outcomes with these treatment approaches have been successful (Stock 2006a).

We are particularly proud of the use of the combined approach for patients with high-risk disease, in which we use nine months of hormonal therapy, a radioactive seed implant and external beam radiation therapy. Recent analyses of this treatment approach show close to an 80 percent biochemical control rate at eight years for patients with high-risk disease (Stock 2004, 2006a), which is impressive.

For our patients with intermediate-risk disease, whom we treat either with an implant and hormonal therapy or an implant and external beam radiation therapy, we’re achieving biochemical control rates in the high 80s and low 90s at 10 years (Stock 2006a).

Track 5

DR LOVE: What are some of the clinical research reports that have been published in the last couple of years that you believe are important for radiation oncologists and urologists to be aware of?

DR STOCK: Some of the most important findings in radiation therapy in general have been the results of the prospective randomized studies that evaluate the use of hormonal therapy combined with external beam radiation therapy.

Two of the most important published trials are the RTOG-9202 study (Hanks 2003; [3.1, 3.2]) and the EORTC-22863 study (Bolla 2002 [4.1, 4.2, pages 20-21]), both of which evaluated long-term hormonal therapy for patients at high risk.

The RTOG trials, and in particular the RTOG-9202 trial that examined the use of two years of hormonal therapy with external beam radiation therapy, have shown the best biochemical control rates for high-risk disease (Hanks 2003).

These trials indicate that we may be able to treat high-risk microscopic metastatic disease in many patients with long-term hormonal therapy, so I’m excited by the data.

In an effort to extrapolate some of the positive outcomes of these trials from our own data, my colleagues and I are examining our data set of patients with particularly high-risk disease treated with combination therapy and trying to analyze the outcomes for those treated with longer-term hormonal therapy.

Track 7

DR LOVE: Would you discuss how you monitor the PSA after brachytherapy and other forms of radiation therapy and how you react to changes in PSA levels?

DR STOCK: A couple of factors are important when following PSA in a patient treated by brachytherapy. One is that it takes about eight months to complete delivery of brachytherapy; radiation from an iodine-125 implant in the prostate will be emitted for about eight months.

The other factor is that it can take up to four or five years following brachytherapy for PSA to hit its nadir. The reason for this is that radiation therapy works by damaging the DNA, and even though cells may be genetically damaged from the radiation from either a seed implant or an external beam, the cells still may produce the PSA protein.

So I believe it’s important to follow these patients carefully but at the same time not to jump to any immediate conclusions.

We also know that because these cells are still making PSA and because brachytherapy can be associated with some late inflammatory reactions, transient elevations in PSA during the follow-up period can occur.

People refer to this as a PSA bounce or PSA spike, which we see in about 30 percent of patients. It is interesting to note that we see this phenomenon more commonly in patients who receive good-quality implants and in young patients.

Therefore, it’s important not to immediately start hormonal therapy in a young patient whose PSA goes up once or even twice after treatment. You have to be patient because many times the PSA levels go back down.

DR LOVE: What do you see in terms of the nadir of PSA with brachytherapy implants versus external beam radiation therapy?

DR STOCK: I believe a difference in PSA nadir is evident. Most of the patients that we treat with brachytherapy implants reach nadir at a level of 0.1 or less. When you cure a patient with external beam therapy and no evidence of biochemical recurrence appears, PSA levels will usually be in the range of about 0.5 to one.

So the difference between these two treatments is significant, and it points to the different biologic effect of dose between a brachytherapy implant and external beam radiation therapy, with an implant able to achieve a higher biologically effective dose compared to external beam radiation therapy.

DR LOVE: What defines a high-quality implant?

DR STOCK: One of the elements that defines a high-quality implant is the dose of radiation delivered to the prostate. One way to measure this is by using a dose-volume histogram, which measures the whole prostate as a volume and doses delivered as percentages of that volume.

Some of our early work at Mount Sinai was to define the D-90, which is the dose to 90 percent of the gland (Stock 2006b).

This method is now appreciated as a very good way of describing the dose delivered to the prostate. For iodine implants, for example, we think that doses, or D-90s, of more than 140 Gray are needed. For palladium, doses of more than 110 Gray are probably necessary.

DR LOVE: What are some of the common questions you hear from urologists and radiation oncologists?

DR STOCK: For many urologists, the major concern is long-term outcomes of brachytherapy. Even though we have data on radiation therapy approaching 15 years, urologists are still commonly concerned with late recurrences.

Radiation oncologists generally do not share that concern because they see the treatment results. They are concerned about how brachytherapy implants compare to the newer modalities of external beam radiation therapy in terms of morbidity, such as urinary symptoms, and how to reduce morbidity.

Therefore, when speaking to radiation oncologists, I often focus on the importance of the technique of implantation and the need to reduce the morbidity commonly associated with it.

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