Video
Clinical Scenario 3: A 76-Year-Old With Metastatic CRPC
Author(s):
Shared insight on a clinical scenario of metastatic castration-resistant prostate cancer managed with androgen-deprivation therapy and docetaxel.
Transcript:
Evan Y. Yu, MD: We are going to go into the third module, which is focused on metastatic castration resistant prostate cancer. This clinical scenario has a 76-year-old gentleman who presents to his primary care physician with bladder outlet obstructive symptoms, reduce urinary flow, hematuria and has pain in his right hip, very concerning. Past medical history is significant for hypertension that’s well controlled with medications. PSA is only 6.4 ng/mL and the patient undergo prostate needle biopsy that reveals a Gleason 8 4+4 adenocarcinoma of the prostate. This patient undergoes conventional staging imaging, a bone scan shows lesions in the right pelvis and CT scan shows lesions in the right lower lobe of the lungs. This patient sounds like he has pulmonary metastasis. ECOG performance status is zero. This patient started on androgen deprivation therapy with abiraterone and low dose prednisone. PSA decreases to 0.2 ng/mL and 15 months later the patient presents with rising PSA of 4.6. This patient undergoes a PET/CT interestingly an FDG PET/CT and this shows enhancing lesions in the lungs and the ribs. Docetaxel is added to his androgen deprivation treatment here and patient tolerates 10 cycles quite well and the PSA nadir has 0.1 ng/mL, however, 5 months later this patient’s PSA is rising and is up to 11.8. Pedro, what are your thoughts on this case. What do you think about this case? Any comments you have about it? How this patient was treated and what might you have done differently?
Pedro C. Barata, MD, MSc: That’s a real-world case. Aggressive disease. This patient presents with high volume disease. We are talking about it with de novo and newly diagnosed metastatic disease, Gleason 8, visual disease with proven metastatic disease in the lung and bones. He is offered one of the combinations that we have been discussing today, ADT and abiraterone. There are a few factors here that caught my eye, and one is the fact that he is progressing 15 months later. When we look at the numbers, for high volume disease it is true that the patients tend to progress sooner rather than later but still we can tell that NHT was not able to hold his disease. If he was today, it is one of the patients I would have considered him for a triple therapy for what we said previously in the context of visual disease, I would have done that. But anyway, the patient progressed – let’s just assume for a second the positive FDG PET showing disease, I am not entirely sure how this was addressed, in my hands I probably would have considered biopsy because as we know prostate is not – we use sugar that’s what FDG is. And we developed this prostate specific tracers because it’s usually prostate cancer does not get that sugar, and therefore it’s suspicious that we see FDG positive disease. It can happen but it’s not those common as other cancers. That would be a case in my opinion for us to consider such an approach if we can. Let’s just assume for a moment we have bread and butter adenocarcinoma features; the patient is on first line therapy docetaxel for 10 cycles and then afterwards you have PSA progression. There are a few things I would have thought. One, we talked about is genomic testing. This patient would need germline and somatic testing because that would help me decide what we’re going to do afterwards. That is one part, the second part is we don’t have scans showing radiographic and/or clinical progression at this point, and it just a reminder that we should not make decisions based on PSA progression because if we do that we run out of options. We are treating the numbers; we are not treating the patient. I am not saying that I am expecting this patient to remain like this for a long time, that’s not the expectation. He does have an aggressive tumor but just to make the point that we need to prove the point that he is progressing in scans in our symptoms. And the next question, if I want to prove this and restage this patient, what am I going to use. That’s going to be depending on where we are in the timing. We are going to consider PSMA scan for this individual because he fits the bill for Lutetium PSMA that is not FDA approved. That’s one option in my book. The other option is obviously if he has homologous recombination deficient gene, I will probably consider him for PARP inhibitor and we can debate what comes first. And then MMR, he will be a patient where immunotherapy could make a lot of sense as well and/or if we get molecular profiling and you have 2 out of 3 TP53, RB1, PTEN then even though you haven’t proven the point of neuroendocrine features, you can come up with reminds you what aggressive prostate cancer for which you probably want to pull the trigger towards cabazitaxel based approach or carboplatin if you will and also it reminds me the car data being important. I know we are going to review all that and it is big list of things but my point with that said is right there. It’s not one size fits all. There is several factors we take into consideration, I will argue in my book this patient would get chemotherapy if I don’t have target lutetium available if I don’t have target therapy available. That probably would be my go-to based on CAR-T. Whether I would add platinum or not, molecular profile would allow me to do that unless of course I have a clinical trial that I would consider.
Mary-Ellen Taplin, MD: Before we get to subsequent therapies, I just want to highlight that this patient at the time they transitioned to CRPC having bone metastasis should also be started on bone supportive agent either denosumab or zoledronic acid, so maybe they were but it’s not stated, and I just think that point bears mentioning.
Andrew J. Armstrong, MD, MSc: Excellent point.
Evan Y. Yu, MD: Would you all have used docetaxel there? I mean there are other options you could use there. This patient progressed on ADT and abiraterone reasonably quickly, would you all have reached for docetaxel or anything else you would have considered?
Andrew J. Armstrong, MD, MSc: It’s worth talking about lung metastasis. Lung metastasis is about 10% to 15% of men with mCRPC but I wouldn’t always assume that this is the CRPC in the lung. Getting a biopsy is helpful, it could be as Pedro mentioned endocrine small cell differentiation. If you knew that you’d treat with platinum based not taxane based regimen. It could be docetaxel plus carboplatin, cisplatin etoposide, lots of different variations. That biopsy could change your management. It could be lung cancer concurrently if he was a smoker. Sometimes we will see PSMA uptake in a lung primary lesion so that can lead to a false positive that you’re treating prostate cancer. A biopsy would be helpful in this case. That would help guide therapy.
Tanya B. Dorff, MD: Pedro’s point about imaging is important because you want to see where the progression is occurring or is there progression occurring. But also, sometimes if everything looks good in the lungs but that hip is starting to hurt again as the PSA is rising you might use some palliative radiation which – there are some publications suggesting that can extend the life of your first AR targeted agent. If they are progressing very slowly asymptomatic, minimally symptomatic. At a slightly lower PSA level, one could have considered sipuleucel-t also as an option, you have to think about how this patient progressing is. This guy probably had visceral, progressed rapidly. That's a scenario where docetaxel makes a lot of sense, especially we could even consider it upfront.
Evan Y. Yu, MD: If this patient didn't have those lung metastases, we could have considered radium as well since the patient was asymptomatic.
Transcript edited for clarity.
%20(2)%201-Recovered-Recovered-Recovered-Recovered-Recovered.jpg?fit=crop&auto=format)
%20(2)%201-Recovered-Recovered-Recovered-Recovered-Recovered.jpg?fit=crop&auto=format)
%20(2)%201-Recovered-Recovered-Recovered-Recovered-Recovered.jpg?fit=crop&auto=format)
