Video
Patient Profile 4: Recurrent Prostate Cancer
Author(s):
Michael Gorin, MD, presents a clinical example of a 60-year-old patient with recurrent prostate cancer.
Neal Shore, MD, FACS: Let’s go to case 4 and let me hand this back to you. And we had a great discussion on high-risk localized disease. Great opportunities to think about PSMA [prostate-specific membrane antigen] PET [positron emission tomography], but how about we move over back to you Mike, and then your ability to have a description in this particular case which is going to springboard us into the CONDOR trial, which is really important. Maybe you can begin by talking about this biochemical relapse case?
Michael Gorin, MD: This is a patient of mine that I saw in clinic. A 60-year-old gentleman who several years ago was diagnosed with grade group 1 prostate cancer with initial PSA [prostate-specific antigen] level of 4.2. At that time, he was elected for treatment with brachytherapy, did well with this and his PSA nadired at undetectable within a year of treatment. About 10 years following his initial treatment, the patient’s PSA level began to rise and most recently his PSA level is 9.3 ng/ml and this has doubled over the last 18 months.
Neal Shore, MD, FACS: These are the types of challenging cases. No one probably would have thought that there was extremely low likelihood that this patient would have evolved here. One could arguably go back and maybe review the histopathology but none the less here you have this doubling time and the ability or the consideration for ordering additional testing. Here are some of the molecular testing guidelines that we have. The ones that are probably most familiar to our colleagues listening would be the Decipher and Oncotype DX or the genomic prostate score in the Prolaris. Certainly, some would get Ki67 looking at just as a general use of cell replication. PTEN loss is not recommended. It’s looked at for clinical trial purposes as part of our ability to understand who is likely to have biochemical or PSA relapse, who is likely to go on to develop metastasis, but let’s go over to the CONDOR trial which in conjunction with OSPREY trial was an important study for our colleagues to be familiar with, and Mike if you can review that, that would be great.
Michael Gorin, MD: The CONDOR trial was a study in the biochemical relapse space. These are patients who have either undergone primary treatment with radiotherapy or radical prostatectomy. They have undergone conventional imaging and by conventional imaging we are talking about bone scan and CT. And that imaging was negative for any sites of disease, except I believe you could maybe see a local recurrence in the prostate that wouldn’t have ruled you out. Then the patients underwent DCFPyL PET scan and then the question was how often in that context would you be able to see a lesion on DCFPyL PET scan and then subsequently to prove that that lesion is prostate cancer, there was a composite truth standard, and the composite truth standard was either biopsy occurred at the site of the disease that was seen on the PET/CT scan. Androgen deprivation therapy [ADT] was administered and a decrease in the PSA level was seen because of it. I believe site directed therapy could have been delivered to a lesion if there was PSA response that was real disease. Interestingly, because Axumin PET had already been approved for prostate cancer imaging, you could trigger an Axumin PET scan and if it was concordant between the Axumin PET and the PSMA PET that was also felt to be a true finding. And then finally you could do a more advanced anatomical imaging test to prove the site was real. For instance, if you saw an uptake in a bone and you ordered something like tumor bone protocol MRI and was able to with this more sophisticated imaging prove that it was metastasis, that would have counted as positive towards the truth standard as well. The diagnostic performance of the imaging test based on that truth standard. The other thing that was done in this study was prior to imaging the patient with PET/CT scan, providers were asked to indicate what the treatment plan would be for the patient based on the conventional imaging and interpretation of PSA doubling time and so forth. And then after the PyL PET scan they were re-asked what the management strategy was for that patient, and this allowed for the measurement of how often treatment plans changed to a significant degree on the basis of this advanced imaging test.
Neal Shore, MD, FACS: It’s a nice review. This concept of truth standard, it was very thoughtful, right? It could be histopathology based on accessing tissue biopsy or surgical extirpation removal, node plucking, and then of course additional imaging correlates of true change and correlate to the finding of the 18F-DCFPyL and then a therapeutic response with PSA as sort of 3 metrics for that. Mike, you want to comment on the baseline characteristics?
Michael Gorin, MD: These patients, a good proportion, about a quarter of them, were high-risk disease at the time of which they were initially diagnosed. Half of all patients underwent radical prostatectomy, so we had a nice mix of radiation therapy, prostatectomy plus salvage radiation, and so forth. I think all different combinations of initial local therapy were well represented in the study population. The other thing that is important about the study is that a lot of patients were enrolled with low PSA levels—roughly one-third of all patients had a PSA level of less than 0.5 and the median PSA level of the study was 0.8. And that’s probably the patient population for whom a PSMA PET scan in the PSA relapse space was probably most useful for because in those patients what you are looking to see is do they have widespread metastatic disease or a local only recurrence because the treatment of those 2 things is so vastly different.
Neal Shore, MD, FACS: That’s a great point that Steven brought up earlier, right? It’s moving back to the pendulum of metastasis-directed therapy. Arguably for some patients, avoiding systemic therapy which invariably would be T suppression vs finding lots of disease or much more high-volume micrometastatic disease which would potentially argue for not only T suppression but even adding androgen receptor pathway inhibitor.
Transcript edited for clarity.
