Case Overview: Metastatic CSPC Follow-Up and Management

Charles Ryan, MD: Back to our case. He has a PSA [prostate-specific antigen] level of 25 ng/mL at the beginning. He goes on ADT [androgen deprivation therapy] and gets chemotherapy. At the end of 6 cycles, the PSA is down quite a bit. It’s not normalized, but it’s 6.2 ng/mL. He’s followed and presumably does quite well because we don’t hear anything from him, and 2 years after that he comes back, his PSA is rising, and he’s on ADT at this time. PSA is 10.8 ng/mL. He’s followed for a bit, and he does ultimately develop worsening symptoms and a rising PSA of 21.4 ng/mL, with a relatively rapid PSA doubling time of about 5.1 months, and he has no new bone lesions that show on imaging.

While this sounds very straightforward, there’s a lot of nuance actually in what’s going on with this case. Should we have followed this patient when he presented with a PSA of 10.8 ng/mL? Should we have started abiraterone on him at that time? Is it appropriate to wait for a patient to develop symptoms before we initiate a new treatment? These are all reasonable questions. However, the use of abiraterone in the CRPC [castration-resistant prostate cancer] setting in an asymptomatic patient is well justified, for 10 years or so, based on the Cougar Biotechnology COU-AA-302 study that led to the approval of abiraterone in that setting. Enzalutamide similarly was demonstrated to have very similar benefits in this setting. So it would have been very reasonable to initiate abiraterone as a PSA of 10.8 ng/mL.

It is a little dismaying that by waiting 5 months, the patient went from being asymptomatic to symptomatic, but that does happen of course. In conversation with patients, many patients choose to wait. They don’t want to be burdened with further therapies. They’re afraid of the monitoring. They don’t want adverse effects. They don’t want the added cost.

Ultimately that is a conversation that takes place between you and your patient about when to consider for therapy. Suffice it to say this patient then starts on abiraterone with a standard dosage of 100,000 mg a day, with prednisone 5 mg twice daily. That is the standard treatment for CRPC. The truth is, we have relatively little data and no real phase 3 data on the efficacy of abiraterone in the setting of CRPC, in which the patient received docetaxel for CSPC [castration-specific prostate cancer], because it remains something of a new clinical space.

But we can still have reasonable expectations for success of this therapy. When I counsel a patient about the use of abiraterone in this setting, I’ll typically offer him an estimate of about a 75% of likelihood that his PSA will go down to 50% or greater and that he’ll be able to be on this treatment for anywhere from 1½ to 2 years based on the depth of that PSA response.

However, in this case he fits into the 25% or 30% or so who may have had an initial reduction in abiraterone, but the PSA continues to rise. He gets a less-than-average benefit from abiraterone in this setting. The PSA ultimately was 30.2 ng/mL, and an abdominal pelvis CT [computed tomography] scan shows multiple new liver lesions. One new vertebral lesion and 1 new appendicular lesion along the spine or the sternum.

This again brings up a little bit of nuance. Recall that when we went back, when his PSA began to rise after the docetaxel, we did a bone scan and saw no new lesions on imaging. It’s very typical that a patient will develop a worsening of disease with a rising PSA but no new bone lesions. That’s what we saw in the beginning. But now when we see this patient developing new boney lesion, that meets our standard academic criteria for radiographic progression, and it also puts him in a position where he is experiencing perhaps more rapid disease progression. Most notably he’s now developed liver metastases, which puts him in a fairly adverse prognostic category.

Even though his PSA is not that high—it’s only 30 ng/mL—we’re seeing a lot of new lesions develop. This does bring up some other concerns that are emerging in the field. Should we biopsy 1 of these liver lesions? While there is very little likelihood that this is not prostate cancer, I believe that over time we’re going to develop a more nuanced understanding of the various histological forms of prostate cancer that can evolve under the treatment pressure of drugs like abiraterone, enzalutamide, or even chemotherapy.

We now know that maybe 20% to 30% of patients in this setting will harbor a neuroendocrine-type disease, or neuroendocrine prostate cancer, which will sometimes be abbreviated as NEPC. This is different from small-cell prostate cancer, which is a very rare disease that is present in maybe 1% of prostate cancer patients. It is generally not associated with hormonal responses and resembles the same types of clinical issues you see when you confront the small-cell cancer in the lung; for example, simply that this is developing in the prostate. The neuroendocrine prostate cancer could be something that is developing here.

We also know through recent publications, for example, that patients developing rapidly progressive disease in the context of what we’d call a relatively low PSA is associated with worse prognosis. And there have been recent publications demonstrating that, showing data on that point, which is something we assumed all along.

Transcript edited for clarity.

Case: A 67-Year-Old Male with Metastatic Castrate-Sensitive Prostate Cancer

Initial presentation

• A 67-year-old active man presented with intermittent back pain and loss of appetite
• PMH: unremarkable
• FH: the patient’s father suffered a myocardial infarction at age 69; paternal grandmother had dementia; no known family history of cancer
• PE: DRE revealed asymmetric enlarged prostate; PE otherwise unremarkable
  
  

Clinical workup

• Core needle biopsy with TRUS showed adenocarcinoma of prostate
  • Stage T2N0M1b
  • Grade group 3
• Bone scan reveal 3 spinal lesions (T10, L2, L3) and 1 near the left iliac crest
• Abdominal and pelvic CT scan showed no other organ metastases
• PSA 24.9 ng/mL
  
  

Treatment and Follow-Up

• The patient was counselled on treatment options; he expressed concern regarding long-term AR exposure
• DOCE + ADT was initiated, 6 cycles were well-tolerated; PSA 6.2 ng/mL
• 2-year follow-up PSA 10.8 ng/mL; continued treatment regimen
  • 5 months later he reported increasing back pain and difficulty walking
  • PSA 21.4 ng/mL
  • PSADT 5.1 months
  • No new bone lesions on imaging
• Abiraterone 1000 mg PO qDay + prednisone 5 mg PO q12hr was initiated
• 1 year later PSA 30.2 ng/mL
  • Abdominal/pelvic CT showed multiple new small liver lesions, 1 new vertebral lesion and 1 new appendicular lesion
• Treatment with cabazitaxel 20 mg/m2 IV q3W + prednisone 10 mg PO qDay was initiated