Chapters Transcript Video Adjuvant vs Salvage Radiation Therapy for Prostate Cancer: New Data Back to Symposium Dr. Jessica Karen Wong presents a discussion on Adjuvant vs Salvage Radiation Therapy for Prostate Cancer: New Data. um I am Karen walderman, an assistant professor of radiation oncology at Fox Chase, specializing in genital urinary malignancies. And I'm happy to speaking to be speaking with you today about new data in agreement versus salvage radiation therapy for prostate cancer. So post prostatectomy radiation is radiation directed to the prostate bed plus or minus pelvic lymph nodes After prostatectomy. As this is the most likely site of recurrence. It's typically directed to the area of the bladder, neck, anterior to the rectum, posterior to the pubic bone and superior to the judea fram. This is a sample post prostatectomy contours with the target of the prostate bed outlined in red with organs at risk including the bladder and the rectum. Also outlined on these slides. The difference in achievement versus salvage radiation. Achievement is given post op based on pathologic findings at the time of surgery. Um Not based on P. S. A. Values. Typically the pizza should be undetectable to technically be adamant radiation and it's delivered in 4 to 6 months. post op to allow for healing salvage radiation is delivered for persistent or rising pizza or recurrent pizza with biochemical recurrence without evidence of distant disease. And it's delivered at the time of PS arise with no regard to distance from surgery itself. The typical guidelines come from the Astro A guidelines. The most recent update was in 2018, which recommended offering adamant radiation to patients with seminal vesicles, invasion, positive surgical margins or extra prostatic extension, offering salvage radiotherapy to patients with P. S. A. Or local recurrence after radical prostatectomy. There's no evidence of distant metastatic disease. Also recommended offering hormone therapy to patients treated with salvage radiation. However, in practice, fewer than 10% of patients with high risk features receive adjuvant radiation nationwide. This could be due to a number of factors, including practice patterns, as well as wanting to avoid extra treatment in patients that may not recur mhm. These data are based off of older adjuvant trials. Uh Typically the three that are shown here, the swab trial, the E. O. R. T. C. Trial and the aero trial. Uh They randomized patients to achievement versus salvage radiation. Um With inclusion criteria of P. E. T. Pathologic T. Three disease or a positive margin. Not all patients had an undetectable P. S. A. And the threshold at this time was 0.2 nanograms per millimeter. Uh Follow up was at least 10 years and biochemical recurrence free survival was actually cut in half with use of vaginal therapy. So on the order of 65% versus 36% at 10 years. The swab trial did show an overall survival benefit but the other two did not. Um So adjuvant radiation was shown to cut the risk of P. S. A. Recurrence by over 50%. Um This was with doses in 62 64 grey range with radiation given between six and 17 weeks post op. So this is good data to show the benefit of adjuvant radiation. However, there are limitations with these trials. The arms weren't truly adamant as a number of patients included on both had a detectable P. S. A. And the not all uh control patients receive salvage. And most often it was late at a higher P. S. A. Um We're talking about PSH values of one point over 1.7. So the question is, are these older trials and the older guidelines applicable in the era of culture sensitive P. S. A. When we're testing more frequently and can intervene sooner as opposed to more of a late salvage treatment. The newer clinical trials include the radical trial, the raves trial and there's youtube trial which looked at specifically answer this question of achievement versus early salvage. The radicals was a two by two trial of achievement versus early salvage with a P. S. A threshold of 0.1. They also looked at different lengths and durations of 80 T. The raves trial um is an Australian trial looking at achievement versus early salvage with A P. S. A. It's your point too. And there's a tube trial is a european trial with a very similar setup. To look in a little bit more detail at one of these trials. The raves trial um involved patients that had radical prostatectomy with one or more high risk factors including a positive margin, extra prosthetic extension or seminal vesicles invasion. And all of them had an undetectable P. S. A. With a threshold of 10.1. They were randomized to either adamant radiation within 4 to 6 months of surgery. For active surveillance with a P. S. A threshold of 60.2 for triggering early salvage radiation actually closed early with fewer biochemical failures than expected. 333 patients were involved, split evenly between the two groups. With a median follow up of six years. Biochemical uh progression was actually equivalent in the two arms. As you can see here. The curves are pretty much superimposed. Five year freedom from biochemical progression was 86% versus 87% and engagement versus salvage. And uh in the salvage group, only about 50% of patients actually had to have radiation due to crossing that s a threshold. Um So if the if you can spare half of your patients an extra therapy with similar outcomes, that seems to be the way to go. Technically the numbers were so low that it did not meet the cut off for non inferiority. So to get a little bit more power, there's a meta analysis of all three of these clinical trials. The radicals trial out of the UK, there's a two european trial and the raves Australian trial, all of which randomized patients between management and salvage early salvage radiation therapy. Looking at the trial characteristics in a little bit more detail. They all have very similar accrual periods in similar key eligibility criteria. However, the radicals trial had a little bit more high risk patients, including both PT for disease as well as highly since for patients they also had a secondary endpoint that was looking at a hyper fractionated regimen. But we don't quite have the data on that yet. Um The threshold for P. S. A. Triggering for salvage treatment was 0.1 in the radicals trial and this 0.2 in the other two patient populations were relatively similar between the three trials as well. The majority of the patients came from the UK radicals trial. Um The patient characteristics for the most part were the same. I would like to highlight that there was very few numbers of T. Four disease patients involved in these trials as well as high gleason score. So eight and above was something on the order of 10 to 15% of all of the patients combined. So in some higher risk patients, these data may not be quite as applicable. Looking at P. S. A driven event free survival. There was an absolute difference of 1% of five years in favor of early salvage. So that hazard ratio overall 1.12 It did cross one. So I wouldn't necessarily say that it proves that early salvage is better but certainly there didn't seem to be any difference in outcomes between early salvage radiation and accident radiation therapy. So how does this impact treatment moving forward for most men? Early salvage should be the preferred treatment. Um I would recommend post op radiation therapy when the pizza is about 0.1 to 0.2. Um It's difficult to say what the low ultra sensitive readings how that might impact it. But certainly getting to a 0.1 or a 0.2 should be a trigger for talking about radiation therapy. However, for younger men at higher risk, recommend continuing with adjuvant radiation as we don't have quite the details for those sorts of patients that would include patients with police and eight or more disease as well as locally advanced disease. And certainly recommend a TT for patients in the savages, sending at least a discussion about it with patients. Mhm. So much Created by Related Presenters Jessica Wong, MD, MEng Assistant Director, Radiation Oncology Residency and Fellowship Training Program Assistant Professor, Department of Radiation OncologyAssistant Director, Radiation Oncology Residency and Fellowship Training Program
