Imaging for mCRPC and Treatment Decisions

Nicholas J. Vogelzang, MD, FASCO, FACP:Let’s talk about imaging. Prostate cancer is well tracked by the use of PSA. The need for imaging is somewhat diminished. But whenever there’s a clinical situation—PSA rise, new symptoms, fatigue, weight loss, minor pain—it’s probably reasonable to reimage because you want to know the disease status. And you need to know whether the disease is bone dominant or non—bone dominant. Now, you can give radium in the face of soft tissue disease, provided the lymph nodes are not overwhelmingly dominant. So, if you have 6-cm lymph nodes and only 1 or 2 bone metastases, you may not want to give radium. You may want to focus on the chemotherapy because, of course, radium will not hit nonosseous metastatic disease.

I always, if I’m about to think about radium, image. I go, “Well, let’s make certain that you don’t have liver, lung, or a large-volume soft tissue lymph node disease.” Small-volume soft tissue disease is fine, but you’ve got to watch it. Because during a time you’re suppressing the bone disease with radium, the soft tissue disease may progress. That’s why I prefer the therapeutic layering. I prefer to give radium for the bone and, at the same time, cover any soft tissue disease in the lymph nodes, for example, with either abiraterone or enzalutamide.

For this particular patient, I probably would have given radium at the time that I started the abiraterone, because then when I give the radium along with the abiraterone, and if they have an abiraterone side effect, I will add the enzalutamide. And by the time I get to the point that enzalutamide is not working at about 6 to 7 months, then I’ll be ready to go to chemotherapy. Because now you’re going, “Well, the enzalutamide is not really working and what about soft tissue disease?” Fortunately, in this case, there’s no soft tissue disease so you’re allowed to go a little bit beyond the radium point, which I would start looking to end. In other words, after 6 cycles, and if the disease starts to progress, that’s when I want to bring in chemotherapy or an alternative antiandrogen.

Given the fact that the second antiandrogen benefit is quite short—and we learned that at ASCO 2017, it’s 3 months—if you get the first antiandrogen, you may get 12 to 15 months on average. That’s the perfect time to give radium. What I do is, for example, if they get abiraterone, their PSA falls nicely, usually stays down for 7 or 8 months, and then you begin to see a little creeping up of the PSA. That’s when I’ll give the radium, because I know that abiraterone is going to fail, probably within 6 to 7 months.

So, I put in the radium right there. If I wait too long, then I’ve got to rely upon the second antiandrogen, such as enzalutamide in this case, and that is only going to give me 3 months. You need to play the chess game with the cancer: what is the cancer thinking? What is the cancer doing? What is its behavior going to be like? And you need those 6 months of radium to be the best you can for your patient with bone-dominant metastatic prostate cancer.

To summarize, bone metastatic disease is extremely common—90% to 95% of patients with prostate cancer. Bone metastases are the major single cause for morbidity and mortality in prostate cancer. Radium is the only directly cytotoxic agent that targets the bone, can prevent bone pain, prevent reduction in quality of life, and extend the life of the patient with bone-dominant metastatic prostate cancer.

Transcript edited for clarity.

November 2014

• A 55-year old gentleman presented with nocturia and PSA level of 4.5 ng/mL
• PMH: Insignificant
• DRE revealed an abnormal area of hardness
• Biopsy showed adenocarcinoma of the prostate gland with a Gleason score 6 [3+3], clinical tumor stage T1c                                                                                                                                                                  
• The patient remained on active surveillance

November 2015

• When he returned after 1 year:
  • PSA, 10 ng/mL
  • Repeat biopsy showed Gleason 7 [4+3] with 8 of 12 cores positive
  • CT scan was negative for metastases
  • He remained asymptomatic
• He was started on a 3-month depot injection of goserelin

February 2016

• PSA, 34 ng/mL
• CT scan was negative for metastases
• He was started on abiraterone and prednisone
  • PSA declined to 15 ng/mL and remained stable
  • After 4 months, he developed cardiac arrhythmia attributed to prednisone; he was switched to enzalutamide
  • PSA remained stable

August 2016

• 3 months following therapy switch, the patient complained of severe fatigue
  • CT scan showed enlarged lumbar spine and pelvic bone metastases
  • ¹⁸F-FDG PET showed increased FDG uptake in several areas of the lumbar spine and pelvis
  • PSA, 45 ng/mL
  • ALP, 225 U/I
• Radium-223 therapy was initiated and enzalutamide was continued
• After 4 cycles of radium-223:
  • Fatigue decreased significantly
  • PSA, 25 ng/mL
  • ALP, WNL
  • CT showed no new bone metastases