Would a high Decipher score affect your recommendation regarding the addition of ADT to XRT in a favorable intermediate risk prostate patient?
The simple answer is YES.
To walk through why...
1. Trials like RTOG 9408 demonstrate that there is a metastasis and OS benefit in Intermediate Risk disease from the addition of short-term ADT to RT.
2. Later work from many groups showed that intermediate risk is a very heterogeneous cohort. This should be obvious, as prognosis is on a continuous scale and NCCN/D'amico risk groups are 3 bins. Great for clinical use, not great for personalized medicine.
3. Zumsteg and colleagues published a retrospective single center study from MSKCC that divided patients into two groups, favorable and unfavorable, based on Gleason grade, PSA, T-stage, and percent positive cores. This study showed like others there is heterogeneity in prognosis, and that there was no apparent benefit of adding ADT to the favorable int risk subgroup. Dr. D'Amico wrote the editorial for this work providing his support for the system, which put the stamp of approval for adoption.
4. Largely based on that study NCCN guidelines adopted this subgrouping.
5. Many subsequent retrospective papers validated the prognostic effect of this subgrouping. An analysis from the D'amico trial also validated this in his ~200 patient RCT, showing that with the RT alone group, there was no PCSM events in the favorable intermediate risk group, and so could not show a benefit. However, this was a very small subset analysis, and other events like metastases are not reported. Thus, there has not been any randomized trial to validate this subgrouping to date, but has largely changed practice.
6. Decipher is one of many prognostic biomarkers, and the only one that is approved for use across all intermediate risk disease, given it has the most robust data currently in this disease space, especially with RT. Simply put, it has shown a consistent ability to improve prognostication over clinicopathologic variables or NCCN subgroupings. This was shown by Berlin et al in IJROBP in a cohort exclusively of intermediate risk. They demonstrated the Zumsteg system had an AUC of ~0.5-0.6 to discriminate patients who will develop metastasis, compared with 0.89 for Decipher. This is consistent with a paper we put out in JCO 2018 that showed that clinico-genomic risk groups had an AUC for metastasis of >0.8 and the Zumsteg system had ~0.65. Additionally, a subset of NCCN favorable intermediate risk disease had high genomic risk disease and behaves much more like an unfavorable intermediate risk patient.
Thus, prognosis is imperfectly captured by a binary division of intermediate risk, and even a continuous model using just our clinical variables is a blunt tool to determine which patients will metastasize after RT alone. Thus, tools that improve our discrimination can help us personalize risk estimates for patients to determine what their absolute benefit will be from the addition of ADT. In the case example, if the average favorable intermediate risk patient has a 10 year metastasis rate of lets say 6-8% with RT alone, in the high Decipher subset this is likely >10%. If ADT has a HR for reduction of metastasis ~0.5-0.6, that would be a 4-5% absolute reduction (40-50% relative reduction) in 10 year metastasis. Most but not all people would find that clinically valuable for the side effect profile of 4-6 months of ADT.
Best,
Dan
Would appreciate some follow-up on favorable intermediate risk with high Decipher.
For instance, a man in his 70s with PSA 4.3 with 2/12 cores G6 a year ago. Follow-up surveillance template 12 core biopsy shows 2 cores G7 (3+4), low volume, and PSA 4.08. Johns Hopkins review of path confirmatory, MRI prostate shows no actionable areas for targeted biopsy. Decipher score is 0.89.
In terms of RT, which options are appropriate? Implant only, SBRT, moderately fractionated RT, EBRT pelvis and prostate, EBRT pelvis and EBRT/seeds?
Or any of these? Is STADT and pelvic nodal therapy always indicated with the high Decipher?