When to Treat Nonmetastatic CRPC

Julie Graff, MD:In January of 2016, this patient has his PSA checked. His PSA was found to be 0.3 ng/ml. And 3 months later, it’s checked again. It’s found to be 0.7 ng/ml. He undergoes imaging studies with a nuclear medicine bone scan and a prostate-specific membrane androgen scan. Both of those studies are negative. We talk to the patient, review the imaging findings, and he does not desire to do any other treatments at this point.

My impression, at this point, is that the PSA seems be going up consistently and quickly. Now, in this situation, it’s typical to check a PSA doubling time, which means looking at the number of weeks, months, or years that it takes for the PSA to double. If it’s under 3 months, 6 months, 10 months, it’s fairly aggressive. If his PSA were doubling every year and a half, I would be less worried. I’m not surprised that this patient didn’t opt to do anything additional at this time. There are no data that say doing anything at this time will improve his outcome, such as time to metastases or survival.

The diagnosis of castration-resistant nonmetastatic prostate cancer typically includes checking imaging studies. It includes making sure that there are no metastases and making sure this patient, or whoever it is, has a castrate level of testosterone, which I don’t see was done at this point. So, doing a blood test to make sure the testosterone is under 50 nanograms per deciliter is typically what we do.

We all know that our imaging studies are not sufficient to detect very small cancer tumors. We can’t detect a grain of rice, for example. But there are newer imaging modalities on the horizon that might eliminate this diagnosis altogether. If we could find something the size of a grain of sand, we might call it metastatic. It’s a little bit of an artificial term that means we can see something on our imaging studies.

When to treat is a tricky question. Some of my colleagues do things very differently. Some of my colleagues don’t treat biochemically relapsed prostate cancer until there is metastases. That’s where all of the data are. Most of my colleagues would treat earlier with the hopes of delaying metastases. I would treat earlier. I don’t know that I would treat at 0.7, but with his PSA doubling the way it is, I might.

I agree with the patient’s decision not to have additional therapy at this time. However, I would counsel him that currently available treatments include the first-generation androgen receptor antagonists, ketoconazole and estrogen.

Transcript edited for clarity.

January 2014

• A 66-year old retired African American male presents with reduced urinary flow and hematuria.
• PMH: High blood pressure. Currently taking enalapril 10 mg.
• FHx: Father lung cancer — age 74.
• Patient walks 3 miles a day.
• PSA 9.8 ng/ml
• Prostate biopsy shows Gleason 7 (4+3) prostate cancer
• Undergoes robotic-assisted laparoscopic prostatectomy (RALP) and pelvic lymph node dissection (PLND)
• Results show:
  • pT3b (focal extracapsular extension and seminal vesicle invasion) — margins negative
  • N1
  • M0
• Post-operative PSA=0.64 ng/ml
• Patient undergoes adjuvant radiation therapy and is started on leuprolide acetate.
• PSA drops to undetectable levels

January 2016

• PSA starts to rise to 0.3 ng/ml
  • Repeated 3 months later — 0.7 ng/ml
  • Bone scan and prostate-specific membrane antigen (PSMA) scan both negative
  • Diagnosis nonmetastatic castration-resistant prostate cancer (CRPC)
  • Patient declines additional therapy at this time

November 2017

• PSA continues to rise over the next 18 months going up to 9.8 ng/ml
• Bone scan shows lesion in the left superior pubic ramus
• Patient is asymptomatic