Tamim Niazi: My pleasure to discuss and also review the data we have presented at ASTRO this year. During ASTRO 2025, we presented our data of phase two randomized trial, which was conducted mainly in Canada across 12 sites, conventional versus hypofractionation, moderate hypofractionation radiation therapy. So again, this was presented on behalf of the Quebec GU Radiation Oncology Group co-investigators, and again, PCS5 was about 330 patients, randomized one-to-one to either a standard fractionation, which we used 76 grays and 38 fractions, 46 grays and 23 to the pelvic lymph nodes, and a sequential boost of 30 grays and 15 fractions to the prostate, plus minus seminal vesicle, depending if the seminal vesicle was involved or not. And the experimental arm was moderate hypofractionation, 68 grays and 25 fractions, concomitant boost to the prostate plus minus seminal vesicle, depending if it was involved, and 45 grays and 25 fractions to the pelvic lymph nodes.
Again, the primary endpoint was acute delayed toxicity, but this data, as was also a couple of years ago, as the efficacy endpoint of this study. Again, we used 68 grays in 25 fraction. If you do the two gray equivalent dose calculation, it comes to about 82 grays, which is importantly higher than 76 grays and 38 fractions.
So if you look at baseline characteristics of the patients, pretty much balanced between the two groups. And importantly, Gleason eight, nine and 10 accounted for over 80% of the patients. Again, make the patients really high risk, and a good percentage of the patient, I think probably two thirds were very high risk if you add the two risk stratifications. Looking at the IMRT versus 3D CRT, again, the study was designed in 2012 and started running at that time. There was still 3D CRT practiced across sites in Canada, but importantly it was pretty balanced between the two arm, about 40 to 50 percent in each group.
Of the 330 patients, very few patients were excluded or withdrawn because of different reasons. At the end, this is the data here with presenting, is about 320 patients having a 10-year outcome data to be analyzed. Important to mention that the toxicity data was actually presented at and published in Journal 2023, I believe, or four, and the efficacy endpoint was published at the European Urology early this year.
Just to rehash the toxicity, just to review, there was pretty much similar acute and delayed toxicity, except a small blip for the acute GI toxicity for moderate hypo, which again subsided, became like the standard fractionation, just within six to seven weeks.
We presented and published our 10-year data, which showed no difference between a standard fractionation and moderate hypofractionation regimen. And this is our 10-year data, which we presented at ASTRO this year, and again, as you can see here, if you look at biochemical relapse-free survival or death, it's again a combination of both counted in this event, at 10-year was 60% or 61% in both groups, non-significant, almost identical curves. Once we remove death from any causes, the biochemical relapse-free survival is 82% between two arms. Pretty decent for high risk, and again, a good percentage more than 50% very high risk disease patients. If you look at metastasis free survival, again, if we include a MFS both death and metastasis, 64% across both arms identical, and if we remove death as an event and distant metastasis only is actually 87%, 88% in both arms, P exact, almost, almost, one.
Looking at the overall survival, again, 68 and 66 percent non-significant. If we remove death from other causes and process, the specific survival was 92 and almost 90 percent between the two arms, which is again no difference between the two groups.
So because of these findings, again it's important to mention that this is the first moderate hypofractionation radiation therapy in high-risk prostate cancer which are treated with contemporary radiation therapy, pelvic radiation therapy, and long-term ADT. Our 10-year results confirms what we have shown at three, five, and seven years, that 68 and 25 fraction is not inferior to 76 grays and 38 fractions for a high risk patient population. And I think we believe that this fractionation should be considered as a standard of care for high-risk prostate cancer patients who are planned to receive external beam radiation therapy and long-term ADT. Thank you.
Leslie Ballas: Thank you Dr. Niazi for presenting these results, and congratulations on presenting your long-term data at ASTRO. I'm interested in the toxicity that you reported. Did you do any sort of breakdown in terms of whether patients who had 3D conformal versus IMRT, or in the population that had a slightly higher GI toxicity, grade one, two toxicity?
Tamim Niazi: If youxfLeslie Ballas: Hi, I'm Leslie Ballas. I'm a radiation oncologist at Cedars-Sinai in Los Angeles, and I am pleased to welcome Dr. Tamim Niazi, who is a associate professor in the division of radiation oncology, department of oncology, at McGill University. He is here today to discuss with us the 10-year outcomes of the Phase III PCS5 trial. Dr. Niazi, thank you so much for joining us today.
Tamim Niazi: My pleasure to discuss and also review the data we have presented at ASTRO this year. During ASTRO 2025, we presented our data of phase two randomized trial, which was conducted mainly in Canada across 12 sites, conventional versus hypofractionation, moderate hypofractionation radiation therapy. So again, this was presented on behalf of the Quebec GU Radiation Oncology Group co-investigators, and again, PCS5 was about 330 patients, randomized one-to-one to either a standard fractionation, which we used 76 grays and 38 fractions, 46 grays and 23 to the pelvic lymph nodes, and a sequential boost of 30 grays and 15 fractions to the prostate, plus minus seminal vesicle, depending if the seminal vesicle was involved or not. And the experimental arm was moderate hypofractionation, 68 grays and 25 fractions, concomitant boost to the prostate plus minus seminal vesicle, depending if it was involved, and 45 grays and 25 fractions to the pelvic lymph nodes.
Again, the primary endpoint was acute delayed toxicity, but this data, as was also a couple of years ago, as the efficacy endpoint of this study. Again, we used 68 grays in 25 fraction. If you do the two gray equivalent dose calculation, it comes to about 82 grays, which is importantly higher than 76 grays and 38 fractions.
So if you look at baseline characteristic of the patients, pretty much balanced between the two groups. And importantly, Gleason eight, nine and 10 accounted for over 80% of the patients. Again, make the patients really high risk, and a good percentage of the patient, I think probably two thirds were very high risk if you add the two risk stratifications. Looking at the IMRT versus 3D CRT, again, the study was designed in 2012 and started running at that time. There was still 3D CRT practiced across sites in Canada, but importantly it was pretty balanced between the two arm, about 40 to 50 percent in each group.
Of the 330 patients, very few patients were excluded or withdrawn because of different reasons. At the end, this is the data here with presenting, is about 320 patients having a 10-year outcome data to be analyzed. Important to mention that the toxicity data was actually presented at and published in Journal 2023, I believe, or four, and the efficacy endpoint was published at the European Urology early this year.
Just to rehash the toxicity, just to review, there was pretty much similar acute and delayed toxicity, except a small blip for the acute GI toxicity for moderate hypo, which again subsided, became like the standard fractionation, just within six to seven weeks.
We presented and published our 10-year data, which showed no difference between a standard fractionation and moderate hypofractionation regimen. And this is our 10-year data, which we presented at Astro this year, and again, as you can see here, if you look at biochemical relapse-free survival or death, it's again a combination of both counted in this event, at 10-year was 60% or 61% in both groups, non-significant, almost identical curves. Once we remove death from any causes, the biochemical relapse-free survival is 82% between two arms. Pretty decent for high risk, and again, a good percentage more than 50% very high risk disease patients. If you look at metastasis free survival, again, if we include a MFS both death and metastasis, 64% across both arms identical, and if we remove death as an event and distant metastasis only is actually 87%, 88% in both arms, P exact, almost, almost, one.
Looking at the overall survival, again, 68 and 66 percent non-significant. If we remove death from other causes and process, the specific survival was 92 and almost 90 percent between the two arms, which is again no difference between the two groups.
So because of these findings, again it's important to mention that this is the first moderate hypofractionation relation therapy in high-risk prostate cancer which are treated with contemporary radiation therapy, pelvic radiation therapy, and long-term ADT. Our 10-year results confirms what we have shown at three, five, and seven years, that 68 and 25 fraction is not inferior to 76 grays and 38 fractions for a high risk patient population. And I think we believe that this fractionation should be considered as a standard of care for high-risk prostate cancer patients who are planned to receive external beam radiation therapy and long-term ADT. Thank you.
Leslie Ballas: Thank you Dr. Niazi for presenting these results, and congratulations on presenting your long-term data at ASTRO. I'm interested in the toxicity that you reported. Did you do any sort of breakdown in terms of whether patients who had 3D conformal versus IMRT, or in the population that had a slightly higher GI toxicity, grade one, two toxicity?
Tamim Niazi: If you look at the acute GI toxicity, which happened very early, and moderate hypofractionation, about six weeks after, it subsided exactly at the level of a standard fractionation. So there wasn't much difference between IMRT and 3D CRT. We published some data, the difference were more GI toxicity if the patients had 3D CRT compared to IMRT, but not much difference GI, I think that we have presented that at ASTRO a year or two ago, and the data is going to be submitted for publication.
Leslie Ballas: Okay, so it's slightly more GI toxicity in the 3D conformal.
Tamim Niazi: Correct.
Leslie Ballas: Which is what we would expect. The other thing, I think, that's very interesting about your toxicity data is that as we follow patients and look at delayed toxicity or late toxicity, we saw just this year moderate hypofractionation in the post-operative setting, that toxicity increased at about 10-plus years. Obviously different anatomy, but it looks really wonderful to have long-term toxicity data for moderate hypofractionation, and then showing that it's really no different than standard fractionation even in the long term.
Tamim Niazi: And I agree, I think given that the efficacy's not different between the two arms and toxicity's almost identical, and there's no new toxicity that arises after 24 months in our seven-year publication in that 10-year analysis, that basically talks for itself that efficacy is the same, toxicity's not different, the same. So it's best to offer the patients 25 days as opposed to 38 or 40 days of treatment.
Leslie Ballas: Your fractionation, you explained you chose for an EQD2 of about, I think you said 82 gray if I'm not mistaken. In the US, commonly moderate hypofractionation is done in 20 fractions of three gray per fraction or either 2.7 times 26 or 2.5 times 28. It seems that your BED is similar to the 26 or 28 fraction regimens, but higher than the 20 fractions at three gray per fraction. Do you think that that EQD2 makes a difference?
Tamim Niazi: It's an important point that you raise. I think if you look at 60 grays in 20 fraction, comes from the CHiP, and the CHiP study, as you know, there was a good percentage, I think if I'm not mistaken about three or four hundred patients, high risk included in that study.
Again, it showed that 57 grays compared to 60 grays were inferior. That means three grays made a difference in that study. And if you do the two-gray equivalent dose using 1.5 alpha beta ratio, the 60 grays comes to about 77 grays, two-gray equivalent, and 68 and 25 comes to about 82 grays. So as a two-gray equivalent, there's a five-gray difference.
So I think again, it's very difficult to cross-compare trials. We shouldn't do that, but just the dose itself, 60 grays and 20 fractions is less. And also in the CHiP trial, pelvis was not treated and long-term ADT wasn't offered. So I think if we really treat patients as a high risk and offering pelvic radiation therapy in long-term ADT, 68 grays and 25 fraction is the only regimen that has been tested with these two aspects of the treatment.
Leslie Ballas: And I think the other thing is that since your trial started, obviously there have been changes in the way that we stage patients with PSMA, there's differences in the way that we use hormone therapy in very high-risk patients, with the addition of ARPIs commonly. How applicable do you think your results are to modern day treatment in 2025?
Tamim Niazi: And again, as you know, when we trial design trials, as time passes, standard changes, new things are added. And when it comes to ARPI, I co-lead the DASL-HiCaP study with Chris Sweeney, and in that study we have allowed 68 grays and 25 fractions with... Again, as you know, the study was darolutamide versus placebo, and again, pelvic radiation therapy. So 68 grays and 25 fraction, I think it will be safe either with or without ARPIs as the standard has changed. And when it comes into pelvic radiation therapy in Canada, we have done a survey. 98 to 99 percent of Canadians do offer pelvic radiation therapy to high-risk prostate cancer patients, and I think they will contribute to do so despite the recent presentation of Dr. Roach at ASTRO.
Leslie Ballas: Yes. I think what Dr. Niazi is referring to is the ASTRO presentation by Dr. Mack Roach of RTOG-0924, looking at the use of pelvic radiotherapy in the unfavorable intermediate, and what they're calling favorable high-risk patients, and that there was at the time point reported no difference in outcomes based on whether or not pelvic radiotherapy was included. Yes, agreed. I think that it's interesting that a trial of 2,500 patients, many people will still do what they believe to be right in terms of adding pelvic radiotherapy or not. Of course, it'll be very interesting to see when Dr. Roach publishes that paper exactly what was classified as favorable high-risk patients. I didn't really get a good sense of that from the presentation.
Tamim Niazi: And I agree, I think teasing out the favorable high-risk, what was the specific criteria of those patients? And as you can see in PCS5 study, the 10 years data, compared to if you... Again, not cross-comparing clinical trials. If you look at all other phase three high-risk trials, just ADT and radiation therapy, our results are pretty robust at 82% at 10 years. That basically tells us that probably, again, more than 50% of the patients were very high-risk, again, and eight, nine, and 10 Gleason score was almost 80-plus percentage. In those patients, probably pelvic radiation therapy is important, but again, it's not a comparative end study, I cannot vouch for it. But for these patient population, I think probably pelvic RT still, in my mind, should be offered.
Leslie Ballas: Yes. And just out of curiosity, what are you doing when you do get PSMA and you find an PSMA avid lymph node? What is your boost dose to the lymph node in question when you're doing this fractionation?
Tamim Niazi: So again, if conventionally identified lymph nodes, we can still do the same fractionation, what we do is that we try to bring the dose, the SIB, or the simultaneously integrated boost, to the lymph node as high as we can get close to the fractionations. Usually I'm hoping to get between 60, 65 grays, but again, sometime the bowel doesn't allow us the rectum or the bladder. If they're further away, it is easier and we can try to boost as much. But in general, I try my best to get above 60 grays.
Leslie Ballas: Wonderful. Dr. Niazi, congratulations on the long-term data presentation. We look forward to hopefully future publication of this, and thank you so much for your time this morning.
Tamim Niazi: And thank you very much for having me, and I think it's an important paper and results to be shared across your platform. look at the acute GI toxicity, which happened very early, and moderate hypofractionation, about six weeks after, it subsided exactly at the level of a standard fractionation. So there wasn't much difference between IMRT and 3D CRT. We published some data, the difference were more GI toxicity if the patients had 3D CRT compared to IMRT, but not much difference GI, I think that we have presented that at ASTRO a year or two ago, and the data is going to be submitted for publication.
Leslie Ballas: Okay, so it's slightly more GI toxicity in the 3D conformal.
Tamim Niazi: Correct.
Leslie Ballas: Which is what we would expect. The other thing, I think, that's very interesting about your toxicity data is that as we follow patients and look at delayed toxicity or late toxicity, we saw just this year moderate hypofractionation in the post-operative setting, that toxicity increased at about 10-plus years. Obviously different anatomy, but it looks really wonderful to have long-term toxicity data for moderate hypofractionation, and then showing that it's really no different than standard fractionation even in the long term.
Tamim Niazi: And I agree, I think given that the efficacy's not different between the two arms and toxicity's almost identical, and there's no new toxicity that arises after 24 months in our seven-year publication in that 10-year analysis, that basically talks for itself that efficacy is the same, toxicity's not different, the same. So it's best to offer the patients 25 days as opposed to 38 or 40 days of treatment.
Leslie Ballas: Your fractionation, you explained you chose for an EQD2 of about, I think you said 82 gray if I'm not mistaken. In the US, commonly moderate hypofractionation is done in 20 fractions of three gray per fraction or either 2.7 times 26 or 2.5 times 28. It seems that your BED is similar to the 26 or 28 fraction regimens, but higher than the 20 fractions at three gray per fraction. Do you think that that EQD2 makes a difference?
Tamim Niazi: It's an important point that you raise. I think if you look at 60 grays in 20 fraction, comes from the CHIP, and the CHIP study, as you know, there was a good percentage, I think if I'm not mistaken about three or four hundred patients, high risk included in that study.
Again, it showed that 57 grays compared to 60 grays were inferior. That means three grays made a difference in that study. And if you do the two-gray equivalent dose using 1.5 alpha beta ratio, the 60 grays comes to about 77 grays, two-gray equivalent, and 68 and 25 comes to about 82 grays. So as a two-gray equivalent, there's a five-gray difference.
So I think again, it's very difficult to cross-compare trials. We shouldn't do that, but just the dose itself, 60 grays and 20 fractions is less. And also in the CHIP trial, pelvis was not treated and long-term ADT wasn't offered. So I think if we really treat patients as a high risk and offering pelvic radiation therapy in long-term ADT, 68 grays and 25 fraction is the only regimen that has been tested with these two aspects of the treatment.
Leslie Ballas: And I think the other thing is that since your trial started, obviously there have been changes in the way that we stage patients with PSMA, there's differences in the way that we use hormone therapy in very high-risk patients, with the addition of ARPIs commonly. How applicable do you think your results are to modern day treatment in 2025?
Tamim Niazi: And again, as you know, when we trial design trials, as time passes, standard changes, new things are added. And when it comes to ARPI, I co-lead the DASL-HiCaP study with Chris Sweeney, and in that study we have allowed 68 grays and 25 fractions with... Again, as you know, the study was darolutamide versus placebo, and again, pelvic radiation therapy. So 68 grays and 25 fraction, I think it will be safe either with or without ARPIs as the standard has changed. And when it comes into pelvic radiation therapy in Canada, we have done a survey. 98 to 99 percent of Canadians do offer pelvic radiation therapy to high-risk prostate cancer patients, and I think they will contribute to do so despite the recent presentation of Dr. Roach at ASTRO.
Leslie Ballas: Yes. I think what Dr. Niazi is referring to is the ASTRO presentation by Dr. Mack Roach of RTOG-0924, looking at the use of pelvic radiotherapy in the unfavorable intermediate, and what they're calling favorable high-risk patients, and that there was at the time point reported no difference in outcomes based on whether or not pelvic radiotherapy was included. Yes, agreed. I think that it's interesting that a trial of 2,500 patients, many people will still do what they believe to be right in terms of adding pelvic radiotherapy or not. Of course, it'll be very interesting to see when Dr. Roach publishes that paper exactly what was classified as favorable high-risk patients. I didn't really get a good sense of that from the presentation.
Tamim Niazi: And I agree, I think teasing out the favorable high-risk, what was the specific criteria of those patients? And as you can see in PCS5 study, the 10 years data, compared to if you... Again, not cross-comparing clinical trials. If you look at all other phase three high-risk trials, just ADT and radiation therapy, our results are pretty robust at 82% at 10 years. That basically tells us that probably, again, more than 50% of the patients were very high-risk, again, and eight, nine, and 10 Gleason score was almost 80-plus percentage. In those patients, probably pelvic radiation therapy is important, but again, it's not a comparative end study, I cannot vouch for it. But for these patient population, I think probably pelvic RT still, in my mind, should be offered.
Leslie Ballas: Yes. And just out of curiosity, what are you doing when you do get PSMA and you find an PSMA avid lymph node? What is your boost dose to the lymph node in question when you're doing this fractionation?
Tamim Niazi: So again, if conventionally identified lymph nodes, we can still do the same fractionation, what we do is that we try to bring the dose, the SIB, or the simultaneously integrated boost, to the lymph node as high as we can get close to the fractionations. Usually I'm hoping to get between 60, 65 grays, but again, sometime the bowel doesn't allow us the rectum or the bladder. If they're further away, it is easier and we can try to boost as much. But in general, I try my best to get above 60 grays.
Leslie Ballas: Wonderful. Dr. Niazi, congratulations on the long-term data presentation. We look forward to hopefully future publication of this, and thank you so much for your time this morning.
Tamim Niazi: And thank you very much for having me, and I think it's an important paper and results to be shared across your platform.