Radiation Therapy vs Surgery Outcomes in High-Risk Localized Prostate Cancer Patients - Soumyajit Roy
March 6, 2025
Neeraj Agarwal speaks with Soumyajit Roy about comparing radiation therapy with surgery for localized high-risk prostate cancer. Dr. Roy discusses his systematic analysis of two major trials—CALGB 90203 (PUNCH) and RTOG 0521—to address the ongoing debate about optimal treatment strategies while awaiting results from the SPCG-15 trial directly comparing these approaches. His findings show radiation therapy plus long-term ADT is associated with lower risk of distant metastasis compared to surgery with post-operative treatment, though this difference disappears when neoadjuvant chemo-hormonal therapy is added to surgery. Dr. Roy emphasizes they're comparing complete treatment regimens rather than simply radiation versus surgery, noting that approximately 80% of high-risk patients undergoing radical prostatectomy eventually need additional treatment. Both physicians conclude that comprehensive multidisciplinary management involving urologists, radiation oncologists, and medical oncologists is essential for patients with high-risk prostate cancer.
Biographies:
Soumyajit Roy, MD, Resident Physician in Radiation Oncology, Rush University Medical Center, Chicago, IL
Neeraj Agarwal, MD, FASCO, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program and the Center of Investigational Therapeutics (CIT), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Biographies:
Soumyajit Roy, MD, Resident Physician in Radiation Oncology, Rush University Medical Center, Chicago, IL
Neeraj Agarwal, MD, FASCO, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program and the Center of Investigational Therapeutics (CIT), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Read the Full Video Transcript
Neeraj Agarwal: Welcome to Dr. Soum Roy, a resident in radiation oncology at the Rush University Medical Center in Chicago. And I would like to start by congratulating you, Soum, first for the oral presentation at the ASCO GU 2025 Prostate Cancer Session. It was really well-received. And also, congratulations for the merit award this year. So a lot of accomplishments so early in your career.
So please tell us about the interesting analysis you did comparing radiation therapy with surgery in patients with localized, high-risk prostate cancer, if I'm not mistaken. So please tell me about your findings, what you did, why you did it, and so on.
Soumyajit Roy: Thank you. Thank you, Dr. Agarwal, for this opportunity. I am thankful to my mentors who have shaped my journey. So without them, I am nothing.
So the thing is that there is always this debate ongoing—what is the appropriate treatment regimen for localized, high-risk prostate cancer? NCCN recommends two major strategies. One is radiation therapy plus long-term ADT. The other is a guideline-concordant approach of radical prostatectomy with personalized post-operative treatment. And we have an ongoing trial, SPCG-15, that will directly address this question. But it’s still ongoing, and we still don’t know when the results will be announced.
So there is an area of doubt here. So what we did is, we did a systematic search and thought that if we include individual patient data from national-level, cooperative group clinical trials that enrolled high-risk prostate cancer patients with contemporaneous enrollment—which is very important, because we are moving very rapidly in terms of evolving management—and also a similar therapeutic question, we would be able to obviate some of the sources of bias and confounding that are there in other retrospective, observational studies, like missing data, nonstandardized treatment, nonstandardized follow-up, no information on treatment compliance, and so on and so forth.
With that thought, we applied a systematic search and found two trials. One is the CALGB 90203, also called the PUNCH study, that randomly assigned high-risk prostate cancer patients to radical prostatectomy with or without neoadjuvant chemo-hormonal therapy. The other was the RTOG 0521, which had radiation therapy plus two years of long-term ADT with or without adjuvant docetaxel.
We chose distant metastasis as our primary endpoint. And the reason for choosing distant metastasis as our primary endpoint was because that’s the most important event—or probably the first most important event—in the life of a high-risk prostate cancer patient. We chose deaths as a competing risk event because the deaths could be from non-cancer-related causes in prostate cancer patients, particularly localized prostate cancer patients.
And we found that, yes, the risk of distant metastasis was lower with radiation therapy and long-term ADT compared to surgery followed by post-operative treatment. And the finding was similar when we just restricted our comparison to the docetaxel arms as well as the standard-of-care arms. But interestingly, when we compared radiation therapy plus long-term ADT to neoadjuvant chemo-hormonal therapy plus radical prostatectomy with post-operative treatment, that difference was mitigated.
So this is very important. What I want people to understand—it is not about radiation versus radical prostatectomy. That is not what we are trying to do here. What we are trying to do here is to compare an RT-based regimen, which has systemic treatment integrated into it, versus an RP-based regimen, which has, again, systemic treatment integrated into it.
So the study probably doesn’t tell us that it is a comparison between RT versus RP. What it tells us is, when you are comparing these two approaches, what is better than the other, or whether there is an equipoise between the two.
And also, we found that the cancer-specific mortality rates were very low in both trial populations, or both the cohorts. And there was no difference. And the reason for that could be, again, these trials were done in the era where we were having more and more ARPI coming into the forefront of management of prostate cancer. And probably even after distant metastasis, patients could be salvaged by these ARPI regimens, and so on and so forth.
Neeraj Agarwal: Which is good news for our patients, right?
Soumyajit Roy: Absolutely. Absolutely.
Neeraj Agarwal: So you took the two trials, contemporary trials—say CALGB trial, RTOG trial—compared radiation therapy with other therapies they got during that time, versus surgery. And distant metastasis-free survival was delayed in the radiation therapy arm, but the overall mortality was similar.
Soumyajit Roy: The cancer-specific mortality was similar, but when we looked at non-cancer-specific mortality, of course, that was—as a little bit expected—higher in the radiotherapy cohort.
Neeraj Agarwal: Because I would assume that people who are chosen to get radiation therapy over surgery—they are usually sicker, older patients in the real world.
Soumyajit Roy: Correct. And unfortunately, even though we had data on most of the baseline characteristics, no trial ever captures the comorbidity data with that level of granularity, and we could not account for that confounder.
Neeraj Agarwal: So please tell me of any trial which is comparing radiation therapy with surgery in this high-risk, localized prostate cancer setting.
Soumyajit Roy: Yeah. So the Scandinavian group—they have the courage to do this study. They are doing it. It’s called SPCG-15, where they are comparing the standard-of-care radiation therapy plus ADT with standard-of-care radical prostatectomy with post-operative treatment in high-risk prostate cancer patients.
Now, there is a little bit of a caveat. They have published their baseline characteristics data in European Urology Open Science journal in 2022. I looked at that, and the cohort has a relatively more favorable risk profile compared to our study population. But I am very excited to see what they show and how we can reconcile our findings—or they can reconcile their findings with ours.
Neeraj Agarwal: Yeah. Very interesting, indeed. And I really agree with you. Kudos to them for being able to do this trial—comparing surgery with radiation therapy?
Soumyajit Roy: Absolutely.
Neeraj Agarwal: What are the final key takeaways for our viewers today from this research?
Soumyajit Roy: So the key takeaways are: of the current NCCN guideline-recommended management options, a radiotherapy-based treatment regimen appears to be associated with a lower risk of distant metastasis compared to a surgery-based treatment regimen in high-risk prostate cancer patients enrolled onto Phase III clinical trials.
Approximately 80% of patients with high-risk prostate cancer who undergo radical prostatectomy would either experience recurrence or would need some kind of post-operative treatment. And thus, it essentially emphasizes the role of early salvage or adjuvant radiation in this context.
I think intensifying systemic treatment with radical prostatectomy and comparing that with radiation therapy plus long-term ADT would probably mitigate some of the observed differences, but cost and toxicity implications require further studies. And we also probably need more evidence to see how to apply these findings in the contemporary clinical practice of widespread use of PSMA PET. And also, Gerhardt Attard published that abiraterone is now standard of care with radiation therapy and long-term ADT in a very-high-risk prostate cancer population. So how to take that into account and think about doing something similar in the future?
Neeraj Agarwal: Thank you very much. So for our viewers, I’d like to give my take on this one. This is great that you were able to conduct such a comprehensive study comparing patient-level data from large Phase III trials. So congratulations to you, to Dr. Spratt, and everybody in the team. This was a massive team effort, it looks like.
And definitely, for me, the message here is that patients with localized, high-risk prostate cancer are at a very high risk of metastasis, relatively speaking, compared to favorable-risk or intermediate-risk disease. And they really need a comprehensive team for management to make sure they don’t develop metastasis or die of their disease. So if somebody comes to me with high-risk prostate cancer for my opinion, I encourage them to see both a radiation oncologist and a surgeon, and hopefully come up with a comprehensive treatment plan in a multidisciplinary fashion.
Soumyajit Roy: And also a medical oncologist, because ARPI would be more and more part of the integrated management regimen for this patient population with evolving time.
Neeraj Agarwal: I agree 100%. Thank you very much, Dr. Roy, for joining us today.
Soumyajit Roy: Thank you. Thank you.
Neeraj Agarwal: And congratulations—
Soumyajit Roy: Thank you so much.
Neeraj Agarwal: —for all your accomplishments.
Soumyajit Roy: Thank you so much. Thank you so much, Dr. Agarwal. I really appreciate this opportunity. Thank you.
Neeraj Agarwal: Welcome to Dr. Soum Roy, a resident in radiation oncology at the Rush University Medical Center in Chicago. And I would like to start by congratulating you, Soum, first for the oral presentation at the ASCO GU 2025 Prostate Cancer Session. It was really well-received. And also, congratulations for the merit award this year. So a lot of accomplishments so early in your career.
So please tell us about the interesting analysis you did comparing radiation therapy with surgery in patients with localized, high-risk prostate cancer, if I'm not mistaken. So please tell me about your findings, what you did, why you did it, and so on.
Soumyajit Roy: Thank you. Thank you, Dr. Agarwal, for this opportunity. I am thankful to my mentors who have shaped my journey. So without them, I am nothing.
So the thing is that there is always this debate ongoing—what is the appropriate treatment regimen for localized, high-risk prostate cancer? NCCN recommends two major strategies. One is radiation therapy plus long-term ADT. The other is a guideline-concordant approach of radical prostatectomy with personalized post-operative treatment. And we have an ongoing trial, SPCG-15, that will directly address this question. But it’s still ongoing, and we still don’t know when the results will be announced.
So there is an area of doubt here. So what we did is, we did a systematic search and thought that if we include individual patient data from national-level, cooperative group clinical trials that enrolled high-risk prostate cancer patients with contemporaneous enrollment—which is very important, because we are moving very rapidly in terms of evolving management—and also a similar therapeutic question, we would be able to obviate some of the sources of bias and confounding that are there in other retrospective, observational studies, like missing data, nonstandardized treatment, nonstandardized follow-up, no information on treatment compliance, and so on and so forth.
With that thought, we applied a systematic search and found two trials. One is the CALGB 90203, also called the PUNCH study, that randomly assigned high-risk prostate cancer patients to radical prostatectomy with or without neoadjuvant chemo-hormonal therapy. The other was the RTOG 0521, which had radiation therapy plus two years of long-term ADT with or without adjuvant docetaxel.
We chose distant metastasis as our primary endpoint. And the reason for choosing distant metastasis as our primary endpoint was because that’s the most important event—or probably the first most important event—in the life of a high-risk prostate cancer patient. We chose deaths as a competing risk event because the deaths could be from non-cancer-related causes in prostate cancer patients, particularly localized prostate cancer patients.
And we found that, yes, the risk of distant metastasis was lower with radiation therapy and long-term ADT compared to surgery followed by post-operative treatment. And the finding was similar when we just restricted our comparison to the docetaxel arms as well as the standard-of-care arms. But interestingly, when we compared radiation therapy plus long-term ADT to neoadjuvant chemo-hormonal therapy plus radical prostatectomy with post-operative treatment, that difference was mitigated.
So this is very important. What I want people to understand—it is not about radiation versus radical prostatectomy. That is not what we are trying to do here. What we are trying to do here is to compare an RT-based regimen, which has systemic treatment integrated into it, versus an RP-based regimen, which has, again, systemic treatment integrated into it.
So the study probably doesn’t tell us that it is a comparison between RT versus RP. What it tells us is, when you are comparing these two approaches, what is better than the other, or whether there is an equipoise between the two.
And also, we found that the cancer-specific mortality rates were very low in both trial populations, or both the cohorts. And there was no difference. And the reason for that could be, again, these trials were done in the era where we were having more and more ARPI coming into the forefront of management of prostate cancer. And probably even after distant metastasis, patients could be salvaged by these ARPI regimens, and so on and so forth.
Neeraj Agarwal: Which is good news for our patients, right?
Soumyajit Roy: Absolutely. Absolutely.
Neeraj Agarwal: So you took the two trials, contemporary trials—say CALGB trial, RTOG trial—compared radiation therapy with other therapies they got during that time, versus surgery. And distant metastasis-free survival was delayed in the radiation therapy arm, but the overall mortality was similar.
Soumyajit Roy: The cancer-specific mortality was similar, but when we looked at non-cancer-specific mortality, of course, that was—as a little bit expected—higher in the radiotherapy cohort.
Neeraj Agarwal: Because I would assume that people who are chosen to get radiation therapy over surgery—they are usually sicker, older patients in the real world.
Soumyajit Roy: Correct. And unfortunately, even though we had data on most of the baseline characteristics, no trial ever captures the comorbidity data with that level of granularity, and we could not account for that confounder.
Neeraj Agarwal: So please tell me of any trial which is comparing radiation therapy with surgery in this high-risk, localized prostate cancer setting.
Soumyajit Roy: Yeah. So the Scandinavian group—they have the courage to do this study. They are doing it. It’s called SPCG-15, where they are comparing the standard-of-care radiation therapy plus ADT with standard-of-care radical prostatectomy with post-operative treatment in high-risk prostate cancer patients.
Now, there is a little bit of a caveat. They have published their baseline characteristics data in European Urology Open Science journal in 2022. I looked at that, and the cohort has a relatively more favorable risk profile compared to our study population. But I am very excited to see what they show and how we can reconcile our findings—or they can reconcile their findings with ours.
Neeraj Agarwal: Yeah. Very interesting, indeed. And I really agree with you. Kudos to them for being able to do this trial—comparing surgery with radiation therapy?
Soumyajit Roy: Absolutely.
Neeraj Agarwal: What are the final key takeaways for our viewers today from this research?
Soumyajit Roy: So the key takeaways are: of the current NCCN guideline-recommended management options, a radiotherapy-based treatment regimen appears to be associated with a lower risk of distant metastasis compared to a surgery-based treatment regimen in high-risk prostate cancer patients enrolled onto Phase III clinical trials.
Approximately 80% of patients with high-risk prostate cancer who undergo radical prostatectomy would either experience recurrence or would need some kind of post-operative treatment. And thus, it essentially emphasizes the role of early salvage or adjuvant radiation in this context.
I think intensifying systemic treatment with radical prostatectomy and comparing that with radiation therapy plus long-term ADT would probably mitigate some of the observed differences, but cost and toxicity implications require further studies. And we also probably need more evidence to see how to apply these findings in the contemporary clinical practice of widespread use of PSMA PET. And also, Gerhardt Attard published that abiraterone is now standard of care with radiation therapy and long-term ADT in a very-high-risk prostate cancer population. So how to take that into account and think about doing something similar in the future?
Neeraj Agarwal: Thank you very much. So for our viewers, I’d like to give my take on this one. This is great that you were able to conduct such a comprehensive study comparing patient-level data from large Phase III trials. So congratulations to you, to Dr. Spratt, and everybody in the team. This was a massive team effort, it looks like.
And definitely, for me, the message here is that patients with localized, high-risk prostate cancer are at a very high risk of metastasis, relatively speaking, compared to favorable-risk or intermediate-risk disease. And they really need a comprehensive team for management to make sure they don’t develop metastasis or die of their disease. So if somebody comes to me with high-risk prostate cancer for my opinion, I encourage them to see both a radiation oncologist and a surgeon, and hopefully come up with a comprehensive treatment plan in a multidisciplinary fashion.
Soumyajit Roy: And also a medical oncologist, because ARPI would be more and more part of the integrated management regimen for this patient population with evolving time.
Neeraj Agarwal: I agree 100%. Thank you very much, Dr. Roy, for joining us today.
Soumyajit Roy: Thank you. Thank you.
Neeraj Agarwal: And congratulations—
Soumyajit Roy: Thank you so much.
Neeraj Agarwal: —for all your accomplishments.
Soumyajit Roy: Thank you so much. Thank you so much, Dr. Agarwal. I really appreciate this opportunity. Thank you.