The Performance of a Genomic Classifier Score in the Phase 3 SAKK 09/10 in Patients with Biochemical Progression - Alan Dal Pra

April 14, 2022

Alan Dal Pra joins Alicia Morgans in a discussion on the SAKK 09/10 trial presented at the 2021 ASTRO meeting. Dr. Alan Dal Pra highlights the efficacy of very intensive versus less intensive radiation in the biochemical recurrent prostate cancer population. This conversation also touches on Decipher® scores and PSA values in these patients.


Alan Dal Pra, MD, Assistant Professor and Associate Director of Clinical Research, Department of Radiation Oncology, The University of Miami Miller School of Medicine

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist at Dana-Farber Cancer Institute in Boston. I am so excited to have here with me today, Dr. Alan Dal Pra, who is an Associate Professor of Radiation Oncology at the University of Miami. Thank you so much for being here with me today, Alan.

Alan Dal Pra: Thanks, Alicia. Thanks for having me.

Alicia Morgans: Wonderful. So I wanted to talk with you a little bit about one of the recently reported trials, the SAKK 09/10 trial or SAKK 09/10 trial, where we really looked at the biochemical recurrent prostate cancer population and tried to understand the efficacy of really intensive versus less intensive radiation. But really also in your analysis, tried to understand the utility of the Decipher test in this patient population. Thank you so much for talking with me about it. And would you mind telling us a little bit about the SAKK 09/10 trial?

Alan Dal Pra: Sure. So the SAKK 09/10 trial was a multicenter, randomized phase III trial that is running at 24 centers in Switzerland, Germany, and Belgium for patients with biochemical progression after prostatectomy. So these patients were randomized to 64 versus 70 Gy to the prostate bed only without concurrent ADT or pelvic nodal radiation. So basically on a median follow-up of six years, there was no difference in freedom from biochemical failure, which was a primary endpoint of the study.

Alicia Morgans: And that of course helped us understand how we dose radiate in this setting. But I would love to hear your secondary analysis, which was really looking at Decipher in this patient population.

Alan Dal Pra: Sure. So we developed a pre-specified statistical plan and this is important because this was prior to the data [inaudible 00:02:00] lock of the trial.  The primary endpoint analysis is to assess the impact of the genomic classifier and the clinical outcomes. So the radical prostatectomy samples were safely reviewed for the highest grade tumor and were run on the Decipher assay. And I studied the time to freedom from biochemical progression according to the Decipher score.  This was the same primary endpoint of the trial.  As a secondary endpoint, we had clinical progression-free survival and [inaudible 00:02:33] received off a salvage hormonal therapy. We also had an exploratory sub-analysis that was the freedom from biochemical progression according to the PSA at randomization. Either early salvage radiation with a PSA less or equal to 0.5 or a late salvage radiation with a PSA higher than 0.5. And importantly, this was a trial stratification variable.

Alicia Morgans: And so, what did you ultimately find?

Alan Dal Pra: So basically we found that Decipher is prognostic for all the endpoints analyzed.  A high Decipher was associated with a higher rate of biochemical progression, clinical progression, and salvage hormonal therapy with a hazard ratio of two to three for these endpoints controlling for all the clinical variables and also for the randomization arm. So there basically there was no difference either in the 70 Gy or 64 Gy arm.

So interestingly, when we assessed the prognostic value of Decipher, according to the PSA at randomization, the curves displayed very important for patients receiving late salvage radiation. Decipher was prognostic only either in the low, early salvage, and late salvage, but when patients were treated with a PSA higher than 0.5, there was a very important separation of the curves. And importantly, for those patients treated with late salvage and a high Decipher, about 90% of them failed within five years. So this means that these patients that really need treatment intensification, and probably salvage radiation to the prostate bed are not enough.

Alicia Morgans: So, Alan, I'm wondering specifically for patients who have a high genomic classifier, is there anything special you would do for them or any recommendations you would have?

Alan Dal Pra: I think these patients need to be treated earlier without waiting for PSA, an increase in PSA because this data actually was very interesting that showed that high GC patients who receive late salvage with a PSA of higher than 0.5, had nearly 90% risk of recurrence by five years post-treatment. So I think this is the patient population that definitely needs treatment intensification.

Alicia Morgans: I completely agree. And I think it's important for us to identify those patients as we can and really do something proactive for them if that is possible.

Alan Dal Pra: Correct. I agree, Alicia.

Alicia Morgans: So I think that's so interesting and really important as we think sort of proactively for the treatment of these patients. How does this kind of information affect the way that you counsel patients today?

Alan Dal Pra: I think it can give us some insight in terms of radiotherapy timing and the need for treatment intensification. I think many oncologists, urologists tend to wait a little bit longer in order to refer patients to radiation oncologists for salvage radiotherapy. I think this gives an insight that patients with a high GC definitely need early salvage. And if they have a PSA higher than 0.5, they need more than salvage radiation to the prostate bed, and probably hormonal therapy and perhaps pelvic radiation as well.

So we can have an idea of timing and intensification. For instance, if we have a patient with a low GC, perhaps we can wait a little bit longer to wait for some of the functional improvements after prostatectomy without any significant impact on biochemical control. Whereas if you have a high-risk GC patient, these patients need to be treated earlier with intensification.

Alicia Morgans: I think that's so important because there are patients who come out of surgery who might have a positive margin, for example, or have some other indication for early radiation. If they have a low Decipher score, perhaps this is a population that we can wait on. And alternatively, of course, if there is a patient population that has this higher genomic classifier decipher score, perhaps we need to do something more proactively or at least be on the very close watch for these patients to have some sort of PSA or other recurrences that we need to do something in addition to radiation, of course, perhaps even adding androgen deprivation therapy and certainly identifying a patient population where a clinical trial could be useful in understanding how to best care for these patients.

So very helpful information. And thank you so much. And I wonder, Alan, how do you use this information or what would your recommendation be for those who are trying to use this information in their clinical practice? What is your sort of summary for them as they are trying to integrate this into their practice algorithm?

Alan Dal Pra: Yeah, I know this is very important because I think Decipher is a very important tool for treatment personalization in the postop setting that definitely needs to be put on the table, together with other assessing comorbidities, life expectancy, frailty scores, some other factors that are absolutely important for postoperative patients. So definitely, I do not think that hormonal therapy will benefit all patients with biochemical progression after prostatectomy and Decipher can help us decide in terms of timing and the use of hormonal therapy and definitely help us personalize this treatment in the postop setting.

Alicia Morgans: Thank you, and I appreciate your insights. I really appreciate you going through this data with us today. Thank you so much for your time and for your expertise.

Alan Dal Pra: Thank you. It was my pleasure.