Nonmetastatic CRPC: Initial Therapeutic Approach

Charles Ryan, MD:This is a relatively typical case one might see in a urology or even a radiation oncology clinic: a 62-year-old man who’s physically active. He has got some cardiac risk factors. He’s diagnosed with a Gleason-7 prostate cancer, a moderately high PSA. He undergoes radical prostatectomy and he has an extra capsular extension, and that puts him at risk for relapse. And so, with a detectable PSA after radical prostatectomy, and in some cases even without a detectable PSA, men will undergo salvage radiation therapy or adjuvant radiation therapy, depending on whether they have a detectable PSA.

So, this patient did that and also received androgen deprivation therapy with his radiation. Now, the use of androgen deprivation therapy with radiation is a little controversial because we don’t have a significant amount of granular data on the duration and the type of it. There are some data that suggested maybe some patients get bicalutamide alone at 150 mg, and very little level 1 data looking at leuprolide, as is done in that case. That said, it’s very common to do it and I do it as well, because we know that the use of hormonal therapy with radiation therapy is generally more effective than radiation alone.

Most patients who present with early prostate cancer don’t have any symptoms. They are found to either have a prostate nodule when their primary care physical does a digital rectal exam, or they have an elevated PSA. Those who do present with symptoms typically will have lower urinary tract symptoms, difficulty voiding, getting up at night to urinate. Sometimes there can be blood in the urine or the semen, but generally, patients are asymptomatic or do not have symptoms.

This patient’s initial testing consisted of a prostate biopsy and a PSA test. We don’t know if other things were done. Many patients nowadays are trying to make a decision about what type of treatment to have. Doing scans for metastatic disease is quite common. This patient’s at very low risk for metastatic disease so it’s not a problem that he did not have a bone scan, for example. There are a series of newer generation genomic tests that can be done in localized prostate cancer that might help determine a patient’s risk of recurrence after radical prostatectomy, for example. But those are still in development in some cases, and many urologists are perfectly fine making treatment decisions without the use of those tests.

This is a very typical treatment course. He’s a young man with a healthy lifestyle for the most part and he’s a surgical candidate. And so, those are patients who could and should be offered surgery and they typically do very, very well. In the hands of an experienced surgeon, many patients will end up with preserved erectile function and preserved urinary continence, although maybe it’s not perfect. But I do agree with the radical prostatectomy in this setting. I further agree with the use of hormonal therapy in the context of salvage radiation therapy, which was given to this patient.

Generally, once patients start ADT, I’ll see them every 3 months and we’ll do a PSA test every 3 months. There’s a lot that can happen with a patient on ADT. It’s not just about bringing down the PSA. You’re taking a man at the age of 62 in this case and you’re reducing his testosterone by 90%. Now, most men have relied on testosterone for a variety of life events and life functions, if you will, since puberty. And so, many patients undergo a pretty profound change when this occurs. They can gain weight, they can experience osteoporosis, and they can get diabetes, which is a known risk of androgen deprivation therapy. Their cardiac risk factors may worsen.

This is a patient, for example, in our case who has some cardiac risk factors. So, if he starts to gain weight as a consequence of his androgen deprivation therapy, we may worsen that cardiac risk. There are potential cognitive changes that can occur. There are potential psychological and even psychiatric changes that can occur. So, I believe it’s actually, while it seems like a benign treatment for the most part, important to get to know your patients and see what their journey is like on androgen deprivation therapy.

Surprisingly, some patients have almost no problem with it and they breeze through it. And even some patients say they feel better on androgen therapy paradoxically. But there are patients who experience real problems from it—depression, mood swings, those types of things—and it’s important to identify who they are.

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