Clinical Cases in Advanced Prostate Cancer - Episode 12

Case 2: Treatment Choices After Progression of Metastatic CRPC

Experts in genitourinary oncology review the treatment choices available after metastatic castration-resistant prostate cancer progression on abiraterone acetate + prednisone.

Jorge A. Garcia, MD, FACP: Here you have someone who walked in the office with de novo metastatic disease and received ADT [androgen deprivation therapy] and docetaxel-based chemotherapy, perhaps by virtue of timing and how our frontline agents got developed. He progressed and went on to receive, in the CRPC [castration-resistant prostate cancer] space, abiraterone acetate. Shortly thereafter, probably within the first 6 months of therapy, he developed bone progression and visceral disease. Mary-Ellen, what would your choices be for sequential therapy for this particular case? Up-front ADT with docetaxel followed by abiraterone acetate.

Mary-Ellen Taplin, MD: Thank you, Jorge. This 72-year-old man with metastatic castration-resistant prostate cancer is notable for a very short response, if any, to abiraterone for CRPC and having liver metastasis. The choice of treatment for this patient may be different from another patient who had a long-term response to abiraterone and only liver metastasis. Looking at the list of options, I would consider chemotherapy next. It wouldn’t be wrong to consider docetaxel, although he’s had it before. I generally like to go to something that the patient’s tumor hasn’t experienced before, so in this case, perhaps cabazitaxel.

The response to enzalutamide after abiraterone in general is poor. In this case, after almost no response to abiraterone, I would not consider enzalutamide. In general, I like to use radium-223 dichloride before chemotherapy, but in a patient with a liver metastasis, I would not. I would need tumor sequencing. An MSI [microsatellite instability]–high tumor, which is very rare, in the order of 3% to 4% before I would consider an immune checkpoint inhibitor. Jorge, my money is on cabazitaxel.

Jorge A. Garcia, MD, FACP: Great. We always talk among ourselves about the transformation syndrome, if you will, where patients may develop neuroendocrine or small cell phenotype. Patrick, as Mary-Ellen mentioned, of the agents that we have in the sequence when we think of therapy for metastatic castration-resistant disease, there are a few that really don’t fit this patient. Perhaps radium-223 dichloride just by the virtue of the presence of visceral disease. As we reviewed today, sequential oral therapy is not the best option for a particular patient who just progressed shortly after another oral agent. Mary-Ellen mentioned to sequence the tumor. The biggest question is: When you think of patients with visceral disease, how often are you and your group in Houston doing biopsies of the liver just to see histology and define genomic testing?

Patrick G. Pilié, MD: Yes, absolutely. This is exactly the patient for whom I’m getting a biopsy and preferably a tissue biopsy at this time rather than a liquid biopsy. That’s because we are wanting to look for neuroendocrine differentiation as well as stains for MMR, or mismatch repair protein. Then we’d look to do DNA sequencing, tumor-associated DNA sequencing, as well as staining for aggressive variant prostate cancer and molecular signature, as all these can influence the next treatment. As already mentioned, going to another androgen receptor signaling inhibitor would not be the right choice in this case, as shown in the CARD trial, which we will present. The other options are biomarker-selected. And then even for next-step chemotherapy, Jevtana is definitely a good choice. But if there is neuroendocrine differentiation or features of aggressive variant prostate cancer, there’s potentially adding carboplatin along with Jevtana.

Jorge A. Garcia, MD, FACP: That’s great. Ganesh, as a urologist you may not see some of these patients late in the game, but certainly your group has and you may be involved at some given time, especially when we’re talking about debulking prostatectomies and so on. Going back to an earlier discussion that we had about the ideal timing for genomic testing, in the sequence of events for someone walking in the office with de novo metastatic disease, when would you actually do genetic testing and specifically counseling germline and somatic?

Ganesh V. Raj, MD, PhD: One of the key things we’ve had during this time of COVID-19 [coronavirus disease 2019] is many more patients than I’ve had before walk in with de novo metastatic disease. One of the things we’ve learned to do is immediately get sequencing, germline or somatic, for anybody walking in with de novo metastatic disease. Ideally, you do a biopsy of any kind of lesion, either the metastatic or the primary, when you get a tissue diagnosis to show that it’s prostate cancer. We almost always send that off for sequencing. This patient would have had sequencing as he walked in the door the first time, and certainly after disease progression with a clearly potentially biopsiable liver lesion as opposed to a bone lesion. We try to avoid bone biopsies. I know in Houston [at The University of Texas MD Anderson Cancer Center] does bone biopsies much more often than we do. We [at University of Texas Southwestern Medical Center] try to avoid that, primarily because we think it’s a little more painful. But a liver lesion is getting biopsied.

Transcript edited for clarity.