Standard of Care for mCRPC

Jorge A. Garcia, MD, FACP: This case is somewhat atypical in my opinion. If you look at his history, this is a patient who presented with what I would define high-risk by NCCN [National Comprehensive Cancer Network] Guidelines just by virtue of a PSA [prostate-specific antigen] over 20 ng/mL. But he had a T2 tumor obviously and a Gleason score of 4+4=8. Now we’re moving away from Gleason, and we’re using the grouping classification. So he had a group 4. That makes him a high-risk patient, obviously. The standard of care for those patients is quite simple. In the absence of metastatic disease, those patients can actually be considered for local definitive therapy with the potential of cure. Most of those patients will either undergo surgical intervention with a radical prostatectomy and a lymph node dissection. Or if the choice is radiation therapy, then patients will undergo radiotherapy with androgen deprivation therapy.

The standard of care for most men with high-risk disease when they elect to undergo local definitive radiation therapy is to use radiation in combination with androgen deprivation or suppression of testosterone. The standard guidelines for most of us is to support 24 months of suppression of testosterone. What is uniquely interesting about this patient is that during his androgen deprivation therapy, he had completed radiation therapy. During his first 6 months of therapy, his PSA did come down. Surprisingly to us, it didn’t come down to undetectable. For most people, one would expect to become undetectable within the first 6 months or so. Those are the people who tend to do the best, in my opinion. However, his PSA did come down to about 11 ng/mL or so. But shortly after, his PSA started rising.

It is very important to remind our audience that 1 of the fundamental keys here is to make sure that the patient has a testosterone-suppressed level. Once you define that, you can actually make determination whether the patient has developed castration-resistant disease, which is very simply defined. It is actually any rising of your PSA, symptomatic progression, or radiographic progression, but in the context or in the setting of a testosterone suppressed level, which for most of us is under 50 ng/mL. There are some pockets of data, and in Europe, they often like to see testosterone [T] levels less than 20 ng/dL. But most of us in our guidelines actually use T level less than 50 ng/dL.

With that, the patient obviously hits that definition of castration-resistant disease. It also happens that this particular patient had developed symptomatic progression by virtue of his intermittent back pain. His bone scan restaging just by virtue of his PSA coming up, oftentimes what we tend to do is repeat staging scans to demonstrate that the patient has not developed progressive disease, objectively speaking. Suddenly, in this case, the patient had progression of disease at the level of the lumbar spine 3 and 4.

So we have a patient with metastatic castration-resistant disease who has some degree of symptomatic progression, by virtue of his intermittent back pain. The bigger question for us is what to do for these patients.

Transcript edited for clarity.

Case:A 69-Year-Old Man with Advanced Castrate Resistant Prostate Cancer

Initial presentation

• A 69-year-old man presented with intermittent back discomfort and loss of appetite
• PMH: hyperlipidemia controlled on a statin, no known family history of cancer
• PE: DRE revealed asymmetric, boggy prostate; otherwise unremarkable

Clinical Workup

• Biopsy with TRUS showed adenocarcinoma of prostate
  • Stage T2N0M0
  • Grade group 4
• Germline genetic testing: MLH1, MSH2, MSH6, PMS2, BRCA1/2, ATM, PALB2 and CHEK2
• Chest/abdominal/pelvic CT scan showed no evidence distant metastases or lymph node involvement
• Bone scan was negative
• PSA 24.9 ng/mL

Treatment and Follow-Up

• EBRT + ADT was started
• Follow up at 6 months, PSA 11.2 ng/mL
• At 12 months PSA 18.6 ng/mL
  • Patient reported increasing back discomfort and difficulty walking
  • Bone scan at that time showed multiple vertebral lesions at L3/L4
• Treatment with radium-223 dichloride was initiate
  • 6 infusions were completed, treatment was well tolerated