PERSIAN Trial Explores SBRT Benefits in Oligometastatic Hormone-Sensitive Prostate Cancer - Giulio Francolini
March 18, 2025
Neeraj Agarwal is joined by Giulio Francolini to discuss the Persian trial examining SBRT added to ADT plus apalutamide in oligometastatic hormone-sensitive prostate cancer. Dr. Francolini explains this 180-patient randomized study was designed to clarify SBRT's benefits in patients with up to five non-visceral metastases, a treatment approach already common in practice despite limited evidence. Preliminary analysis of 87 patients shows a trend favoring the SBRT arm, with statistically significant improvement in complete biochemical response (PSA <0.2 ng/mL) already evident in patients with fewer than three metastatic sites. No increased side effects are observed when combining SBRT with androgen receptor pathway inhibitors. Dr. Francolini suggests these improved response rates could potentially enable treatment holidays, allowing patients to regain testosterone.
Biographies:
Giulio Francolini, MD, Radiation Oncologist, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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:
Giulio Francolini, MD, Radiation Oncologist, Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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
Related Content:
ASCO GU 2024: Apalutamide and Stereotactic Body Radiation Therapy for Low-Burden, Metastatic, Hormone-Sensitive Prostate Cancer: A Randomized Trial (PERSIAN)
ASCO 2021: Health-Related Quality of Life and Patient-Reported Outcomes at Final Analysis of the TITAN Study in Patients with Metastatic Castration-Sensitive Prostate Cancer
ASCO GU 2024: Apalutamide and Stereotactic Body Radiation Therapy for Low-Burden, Metastatic, Hormone-Sensitive Prostate Cancer: A Randomized Trial (PERSIAN)
ASCO 2021: Health-Related Quality of Life and Patient-Reported Outcomes at Final Analysis of the TITAN Study in Patients with Metastatic Castration-Sensitive Prostate Cancer
Read the Full Video Transcript
Neeraj Agarwal: Welcome to Dr. Giulio Francolini, the radiation oncologist from the University of Florence, to UroToday. First of all, I'd like to congratulate you for presenting the result of the PERSIAN trial, looking at the role of SBRT in patients with oligometastatic prostate cancer who were undergoing treatment with androgen deprivation therapy with apalutamide. So first of all, welcome.
Giulio Francolini: Thank you very much.
Neeraj Agarwal: So tell me, what made you do this trial?
Giulio Francolini: Basically, in clinical practice in many countries, these patients undergo SBRT on top of their systemic treatment, and it's a really safe treatment. But overall, we do not know the real benefits of adding a local treatment in an oligometastatic patient. So the trial was designed in order to show the real benefits of adding this treatment on top of a standard-of-care treatment.
Neeraj Agarwal: So patients are already getting this SBRT, but we do not know the benefit exactly?
Giulio Francolini: Yes.
Neeraj Agarwal: What kind of benefit or even side effects they have.
Giulio Francolini: Yes.
Neeraj Agarwal: As you said, it's a very safe therapy, but it's good to have a trial to answer that question. So can you please tell us about the design of the trial and how many patients were there, and how did you treat them with SBRT?
Giulio Francolini: Patients enrolled in the PERSIAN trial are oligometastatic hormone-sensitive prostate cancer in a metachronous scenario with no more than five known metastases detected on conventional imaging (no visceral metastases). They are treated with ADT plus apalutamide in both arms and randomized to receive or not SBRT on all metastatic sites of disease. The total sample size is 180 patients, and the enrollment ended in November 2024.
On the current abstract, we presented the results about the first 87 patients reaching three months of follow-up after the start of treatment, with a focus on complete biochemical response defined as PSA lower than 0.2 ng/mL. And basically, results show that in patients—
Neeraj Agarwal: Well, I'll come to the result in a moment.
Giulio Francolini: OK, sorry.
Neeraj Agarwal: Thank you very much for explaining this. So you're saying that you have recruited 180 patients with metastatic hormone-sensitive prostate cancer who have oligometastatic disease, and you said less than five metastases, no visceral metastases.
Giulio Francolini: No visceral metastases.
Neeraj Agarwal: So I wanted to make sure we are clear on that. The patient could not have visceral metastases—
Giulio Francolini: No.
Neeraj Agarwal: —but they could have up to five bone metastases.
Giulio Francolini: Bone or nodal.
Neeraj Agarwal: Bone or nodal, OK.
Giulio Francolini: Yes.
Neeraj Agarwal: So lymph nodes are allowed—
Giulio Francolini: Yes.
Neeraj Agarwal: —basically. And did you randomize these patients?
Giulio Francolini: Yes.
Neeraj Agarwal: So you randomized—out of 180 patients, you randomized them to ADT plus apalutamide versus ADT plus apalutamide plus SBRT.
Giulio Francolini: Yes.
Neeraj Agarwal: Great. So primary endpoint of less than 0.2. That's the primary endpoint?
Giulio Francolini: The primary endpoint is PSA lower than 0.2 after six months.
Neeraj Agarwal: After six months.
Giulio Francolini: Yes.
Neeraj Agarwal: Which we know is a surrogate for overall survival, coming from multiple clinical trials in metastatic hormone-sensitive prostate cancer. So please tell us about the results.
Giulio Francolini: Basically, in the first 87 patients, at three months, we saw trends in terms of advantage for the experimental arm with an odds ratio of 1.27 and a significant benefit in patients with less than three metastatic sites. And this is quite interesting because of course, the lower the burden of disease, the higher the benefit. And we will see if these results will be confirmed in the complete cohort. The primary endpoint will mature in June 2025 because we ended the enrollment in November 2024.
Neeraj Agarwal: So it's interesting that there is already a trend for all patients, but it is already significant. So a difference in PSA of less than 0.2 ng/mL responses at six months is already significant in patients who have three or fewer sites of bone metastasis. So it means it looks like SBRT is already panning out in low-volume disease who have less than three metastasis sites.
Giulio Francolini: Yes.
Neeraj Agarwal: Is that correct?
Giulio Francolini: Yes.
Neeraj Agarwal: OK. That's great. Any side effects? Any side effects you'd like to mention?
Giulio Francolini: Actually, the concomitant administration of SBRT and ARPI does not increase the side effects of both treatments. And we saw a similar trend even in our previous trial we conducted in our institution, which was the ARTO trial using abiraterone in castration-resistant prostate cancer. But we didn't see any increase in terms of side effects from SBRT given concomitantly with ARPI.
Neeraj Agarwal: Which we know is a pretty well-tolerated modality to treat patients. So just to summarize, in the prelim analysis of 87 patients—
Giulio Francolini: Mhm.
Neeraj Agarwal: —who were randomized to ADT plus apalutamide versus ADT plus apalutamide plus SBRT, you are already seeing significant differences in undetectable PSA responses, defined as PSA of less than 0.2 after six months of treatment with ADT plus apalutamide when you add SBRT to the regimen.
Giulio Francolini: Yes.
Neeraj Agarwal: And the trend is trending in favor of the SBRT in patients who have up to five bone metastases—
Giulio Francolini: Yes.
Neeraj Agarwal: —without any noticeable side effects.
Giulio Francolini: No.
Neeraj Agarwal: What is the takeaway for our listeners, our viewers who will be looking at this video? From the master, what is the message?
Giulio Francolini: I think that in an oligometastatic scenario, we should go for a local treatment and extend the indication for SBRT, because besides the results in terms of complete biochemical response that we show, we could think that if the patients have an increased rate of complete biochemical response, maybe some of these patients could have a holiday from treatments as well, given the significant decrease in terms of PSA they receive from the complete treatment of ADT plus apalutamide plus SBRT.
Neeraj Agarwal: And that may be the best thing coming out of this trial.
Giulio Francolini: Yes.
Neeraj Agarwal: Because I have not come across a single patient who is happy with having no testosterone, pretty much. So if you are saying this SBRT can allow some of the patients to have long-term undetectable PSA responses after receiving ADT, they may have treatment holidays and allow them to have their testosterone back, which will be a fantastic outcome. So we look forward to the final results in the next year by ASCO and hope to meet again here on UroToday to discuss the final results. But congratulations for doing this meaningful study, and thank you for joining us today.
Giulio Francolini: Thank you very much.
Neeraj Agarwal: Welcome to Dr. Giulio Francolini, the radiation oncologist from the University of Florence, to UroToday. First of all, I'd like to congratulate you for presenting the result of the PERSIAN trial, looking at the role of SBRT in patients with oligometastatic prostate cancer who were undergoing treatment with androgen deprivation therapy with apalutamide. So first of all, welcome.
Giulio Francolini: Thank you very much.
Neeraj Agarwal: So tell me, what made you do this trial?
Giulio Francolini: Basically, in clinical practice in many countries, these patients undergo SBRT on top of their systemic treatment, and it's a really safe treatment. But overall, we do not know the real benefits of adding a local treatment in an oligometastatic patient. So the trial was designed in order to show the real benefits of adding this treatment on top of a standard-of-care treatment.
Neeraj Agarwal: So patients are already getting this SBRT, but we do not know the benefit exactly?
Giulio Francolini: Yes.
Neeraj Agarwal: What kind of benefit or even side effects they have.
Giulio Francolini: Yes.
Neeraj Agarwal: As you said, it's a very safe therapy, but it's good to have a trial to answer that question. So can you please tell us about the design of the trial and how many patients were there, and how did you treat them with SBRT?
Giulio Francolini: Patients enrolled in the PERSIAN trial are oligometastatic hormone-sensitive prostate cancer in a metachronous scenario with no more than five known metastases detected on conventional imaging (no visceral metastases). They are treated with ADT plus apalutamide in both arms and randomized to receive or not SBRT on all metastatic sites of disease. The total sample size is 180 patients, and the enrollment ended in November 2024.
On the current abstract, we presented the results about the first 87 patients reaching three months of follow-up after the start of treatment, with a focus on complete biochemical response defined as PSA lower than 0.2 ng/mL. And basically, results show that in patients—
Neeraj Agarwal: Well, I'll come to the result in a moment.
Giulio Francolini: OK, sorry.
Neeraj Agarwal: Thank you very much for explaining this. So you're saying that you have recruited 180 patients with metastatic hormone-sensitive prostate cancer who have oligometastatic disease, and you said less than five metastases, no visceral metastases.
Giulio Francolini: No visceral metastases.
Neeraj Agarwal: So I wanted to make sure we are clear on that. The patient could not have visceral metastases—
Giulio Francolini: No.
Neeraj Agarwal: —but they could have up to five bone metastases.
Giulio Francolini: Bone or nodal.
Neeraj Agarwal: Bone or nodal, OK.
Giulio Francolini: Yes.
Neeraj Agarwal: So lymph nodes are allowed—
Giulio Francolini: Yes.
Neeraj Agarwal: —basically. And did you randomize these patients?
Giulio Francolini: Yes.
Neeraj Agarwal: So you randomized—out of 180 patients, you randomized them to ADT plus apalutamide versus ADT plus apalutamide plus SBRT.
Giulio Francolini: Yes.
Neeraj Agarwal: Great. So primary endpoint of less than 0.2. That's the primary endpoint?
Giulio Francolini: The primary endpoint is PSA lower than 0.2 after six months.
Neeraj Agarwal: After six months.
Giulio Francolini: Yes.
Neeraj Agarwal: Which we know is a surrogate for overall survival, coming from multiple clinical trials in metastatic hormone-sensitive prostate cancer. So please tell us about the results.
Giulio Francolini: Basically, in the first 87 patients, at three months, we saw trends in terms of advantage for the experimental arm with an odds ratio of 1.27 and a significant benefit in patients with less than three metastatic sites. And this is quite interesting because of course, the lower the burden of disease, the higher the benefit. And we will see if these results will be confirmed in the complete cohort. The primary endpoint will mature in June 2025 because we ended the enrollment in November 2024.
Neeraj Agarwal: So it's interesting that there is already a trend for all patients, but it is already significant. So a difference in PSA of less than 0.2 ng/mL responses at six months is already significant in patients who have three or fewer sites of bone metastasis. So it means it looks like SBRT is already panning out in low-volume disease who have less than three metastasis sites.
Giulio Francolini: Yes.
Neeraj Agarwal: Is that correct?
Giulio Francolini: Yes.
Neeraj Agarwal: OK. That's great. Any side effects? Any side effects you'd like to mention?
Giulio Francolini: Actually, the concomitant administration of SBRT and ARPI does not increase the side effects of both treatments. And we saw a similar trend even in our previous trial we conducted in our institution, which was the ARTO trial using abiraterone in castration-resistant prostate cancer. But we didn't see any increase in terms of side effects from SBRT given concomitantly with ARPI.
Neeraj Agarwal: Which we know is a pretty well-tolerated modality to treat patients. So just to summarize, in the prelim analysis of 87 patients—
Giulio Francolini: Mhm.
Neeraj Agarwal: —who were randomized to ADT plus apalutamide versus ADT plus apalutamide plus SBRT, you are already seeing significant differences in undetectable PSA responses, defined as PSA of less than 0.2 after six months of treatment with ADT plus apalutamide when you add SBRT to the regimen.
Giulio Francolini: Yes.
Neeraj Agarwal: And the trend is trending in favor of the SBRT in patients who have up to five bone metastases—
Giulio Francolini: Yes.
Neeraj Agarwal: —without any noticeable side effects.
Giulio Francolini: No.
Neeraj Agarwal: What is the takeaway for our listeners, our viewers who will be looking at this video? From the master, what is the message?
Giulio Francolini: I think that in an oligometastatic scenario, we should go for a local treatment and extend the indication for SBRT, because besides the results in terms of complete biochemical response that we show, we could think that if the patients have an increased rate of complete biochemical response, maybe some of these patients could have a holiday from treatments as well, given the significant decrease in terms of PSA they receive from the complete treatment of ADT plus apalutamide plus SBRT.
Neeraj Agarwal: And that may be the best thing coming out of this trial.
Giulio Francolini: Yes.
Neeraj Agarwal: Because I have not come across a single patient who is happy with having no testosterone, pretty much. So if you are saying this SBRT can allow some of the patients to have long-term undetectable PSA responses after receiving ADT, they may have treatment holidays and allow them to have their testosterone back, which will be a fantastic outcome. So we look forward to the final results in the next year by ASCO and hope to meet again here on UroToday to discuss the final results. But congratulations for doing this meaningful study, and thank you for joining us today.
Giulio Francolini: Thank you very much.