This video features Jessica Karen Wong, MD, MEng presenting on Adjuvant vs. Salvage Radiation Therapy for Prostate Cancer: New Data. This presentation was given at our November 9th Optimizing Treatment Strategies for Localized and Advanced Prostate Cancer CME in 2022.
Thank you guys so much for having me. Like he said, I'm Karen Wong. I'm one of the radiation oncologist specializing in Guiyu at Fox Chase and I'm happy to speak to you today about achievement versus salvage radiation therapy. So this all falls under the topic of post prostatectomy radiation. All of this is done after. Guys have chosen to have primary surgical management of their localized prostate cancer. And treatment afterwards can be done to reduce the risk of local recurrence. Typically the most common place for recurrence after a prostatectomy is right in the area of the surgical bed, typically right around the anastomosis site. And treatment with radiation can be directed to specifically this area with the prostate bed plus or minus pelvic lymph nodes as well after prostatectomy to reduce that risk of recurrence. This is what sample contours for a prostate bed look like. This is a sample patient. The area in red is the prostate bed itself that we target with the radiation with the bladder and yellow and the rectum in brown. We are targeting that space in between the bladder and the rectum while encompassing a large amount of the bladder neck as well as the anastomosis site. As well as you can tell, there is a lot of normal tissue here. It's a very narrow area. There's a lot of things that we're worried about affecting with radiation. As you heard from the previous talk this area is very sensitive and so to be able to do this safely. We have to be sure that we're using proper image guidance and how best to deliver this sort of radiation. Typically it's done in a very conventional slow and steady sort of way that's done over something like seven weeks of radiation with daily treatment Monday through Friday or something like 34 total treatments in other areas of prostate cancer. We can do this a little bit faster to be able to get patients through um in a more convenient manner. But because of the amount of normal tissue that is in the field that you're trying to treat in this particular setting that hasn't been able to be the case. So talking about achievement versus salvage, what does this actually mean? Adjuvant treatment is typically given um post op radiation based off of the pathologic findings at time of surgery regardless of the P. S. A. It is typically given very soon after surgery with enough time given for healing. So typically about 4 to 6 month post op salvage treatment is done in reaction to recurrent P. S. A. Uh With biochemical recurrence or maybe potentially persistent P. ECE after surgery. And typically historically this was done years following a prostatectomy. As we could see that P. S. A. Continuing to climb and climb before getting started with these sorts of treatments. Biochemical recurrence is what we consider a significant rise in P. S. A. After prostatectomy. Um The standard phoenix definition of biochemical recurrence is typically a P. S. A. Of 0.2 nanograms for military um That's thought to be significant enough to indicate the potential for residual prostate cancer is still in the patient but at the time that this was decided on, as the consensus, the lowest detectable psa was 0.2 nanograms for middle leader. So is this still applicable in a time where we have ultra sensitive PSAs and we can catch this a little bit sooner. The main white paper guidelines with Astro, the American Society for Radiation Oncology in the a way um came together to give a little bit of guidance in this sort of area. Last updated in 2019. Um with recommendations to offer adjuvant radiation to patients with more locally advanced disease, such as seven of us. School invasion positive surgical margins or extra prosthetic extension and offering salvage radiation to patients with local recurrence or biochemically recurrent disease with no evidence of metastatic disease. Plus or minus the option of hormonal therapy in patients with salvage radiation. And we'll get into that a little bit more later. But even though this Is the recommendation in practice, this doesn't always get followed, particularly for a German patients, fewer than 10% of patients with higher risk of features do actually go on to receive adjuvant radiation. And even salvage treatment, adoption rates are somewhat lower than we would like them to be. So older achievement trials looked at intervening um based off of pathologic findings versus continuing to watch these patients. Um These are the three main trials that that established this as a treatment of choice um included patients with more higher risk disease, like the seminal vesicles involvement or extra capsule extension and a positive margin. They followed them for something on the order of a decade and found improvements in biochemical recurrence free survival as well as a potential overall survival benefit. With this sort of treatment, radiation doses was kind of like I described before 60-64. Gray radiation was between six and 17 weeks. Post op and adjuvant radiation cut the risk of recurrence by over 50%. However, these are older trials. Um The agin Arms were not truly advent. A lot of them did have detectable P. S. A. S. At that time and in the control groups, not everyone received salvage. It was more of a comparison of intervention versus no intervention. Only about a third to a half of patients on the salvage arms actually did end up getting any salvage radiation treatment. So newer clinical trials focus more in a modern setting with lower P. S. A. S. And more early intervention on the salvage side of things. Uh These are three separate trials done in three separate parts of the world that all kind of looked at the same sort of thing. The radical trial also looked at the role of A. T. T. In these sorts of patients as well. So focusing on just one of them. The race trial was done in Australia. New Zealand and it was involving patients with higher risk factors including positive margin, extra prostatic extension and seminal vesicles invasion that all had undetectable P. S. A. S. And they were stratified based off of these various risk factors and received either adjuvant radiation within 46 months of of surgery versus active surveillance. And all of these patients got close P. S. A. Follow up with intervention. Once that? S across that 0.2 threshold, about half of the patients in the salvage group did go on to have radiation due to a P. S. A. Rise. Um And 5% freedom from biochemical progression was 86% versus 87% in salvage. So really no difference between those two arms. Um Since the numbers were lower, they technically did not meet cut off for non inferiority. But you can see those numbers are very similar. And if you can spare about half of your patients from actually getting an additional intervention, I think there's a benefit to being able to just watch and intervene early. Should it be necessary. A meta analysis. Looking at all three of these different trials, they all came out around the same time uh to get a little bit more statistical power and see um what we can do with all of this information looked at the three of them. They're very similar in scope um as well as in time frame of the cruel periods. Um the of notes the radical trial had a little bit more inclusion of higher risk gleason scores of 7-10. Um As well as had an option for hyper fraction nation in uh in certain subsets of patients, patients uh were very similar between the different studies with a much higher patient population in the radicals trial. Um As also to note with looking specifically at gleason scores, very few patients were involved with gleason score eight or higher. So this may not be the most applicable to very high risk patients that have higher gleason scores and other higher risk factors. So looking at all the data together, um P. S. A driven event. Free survival was compared between these and overall. Um There was an absolute difference of 1% at five years favoring actually early salvage. So really very little difference between early salvage and adjuvant treatment. So, if we can spare some patients, but additional treatment um just based off of their surgical features and the ones that actually do have a P. S. A rise to intervene early seems to be the best option. There may still be patients that benefit from adjuvant radiation. Like we said before. Um Some of the patients with higher risk factors weren't as well represented in these trials. That showed no difference. So, looking at patients that do have higher risk factors like the more locally advanced disease, higher gleason score, lymph node involvement or higher genomic classification scores, patients with higher risk factors do seem to benefit a little bit more from that. Adjuvant radiation so should still be considered in certain circumstances. The role of A. D. T. With salvage radiation is also still a little bit under debate. Um There are a few trials that do show benefit of A. D. T. On top of concurrently with post prostatectomy radiation. The style study looked at six months of androgen suppression and show to benefit um over radiation alone and this is concordant with an overall survival benefit seen in the older R. T. O. G 96. So one trial um which use 24 months of 80 t. However this does need to be balanced by overall benefits and risks. Not everyone is a great candidate for A. T. T. Or or on a lot of patients potentially want to avoid that and that's why they lean a little bit more towards radiation in these sorts of situations. So it's all a benefit uh and risk balance for these sorts of patients. The role of pelvic nodal radiation. The original contours I showed you earlier just were reflective of the prostate bed itself. This is an extension of a debate in radiation oncology and the more intact setting um electively treating pelvic nodes in higher risk patients. And is there a benefit to that in the post prostatectomy setting. The traditionally it hasn't really been covered as much unless there is something of a higher risk factor positive lymph nodes on at the time of surgery. Things like that. But this sport trial did show a benefit of adding on pelvic nodal radiation on top of A. D. T. As well as prostate bed radiation alone. Um It does come with the trade off of slightly higher short term toxicity rates particularly bowel toxicity as you're covering larger volumes of small about future directions. Um Talking about hyper fraction ation like I talked about before that uh an area that hasn't really been used very much in a post prostatectomy setting that's giving more radiation with each fraction to get you through a course of radiation faster so it can decrease treatment times and make things a lot more convenient for patients. But going at a shorter rate can come with a little bit more side effects. So it has has it been adopted? This is one of the kind of strongholds of the conventional fraction nation because there is much more normal tissue in the area that you're trying to treat. There are current trials looking at patients in the post prostatectomy setting. Looking at doing more hyper fractionated radiation and potentially with better image guidance, we can find ways to be able to do this safely and effectively overall early salvage radiation remains underutilized in this particular michigan study. Um Only about 26 patients received early salvage even after the P. S. A threshold of 0.2. Um A lot of times. People still wait until that P. S. A. Continues to climb a bit more. So I think earlier adoption um is key to making sure these patients get the treatment that they need. So once they have detectable P. S. A. It's always worth referring to radiation oncology. It may not be the time to go ahead and get started but you might as well hear about it. It's probably something that might be in their future. So in conclusion for most men, early salvage radiation is the preferred treatment post operatively. Typically when the P. S. A. Is about 0.2 nanograms per milliliter for patients that you're particularly worried about younger patients that have a lot of life ahead of them as well as high risk disease. There is still a role for adjuvant radiation and those patients should still consider it. Um Once we get started talking about salvage treatments, adding on A. T. T. As well as potentially pelvic lymph nodes for high risk patients as well. All right. Thank you all so much.