Impressions of a Patient With Progression to mCRPC

Daniel J. George, MD:This is a case of a 71-year-old gentleman who initially presented with some urinary obstructive symptoms and was found to have a PSA [prostate specific antigen] of 10.2 in a nodular prostate on exam. He underwent transrectal ultrasound and biopsy and was found to have multiple cores of Gleason 9 cancer and elected for prostatectomy, which confirmed these findings along with stage III disease and extracapsular involvement. After surgery and recovery of his symptoms, he was treated with adjuvant hormonal therapy, with leuprolide, and with IMRT [intensity-modulated radiation therapy]—7800 cGy. Unfortunately, his PSA reached a nadir but continued to rise on hormonal therapy until 2016, in April, when his PSA reached up to 47.

At this point in time, his scans were still negative for disease but he was clearly castration-resistant and was started on enzalutamide therapy. He initially tolerated this well and had a nice decline in PSA—down to 12. However, after that nadir, his PSA began to rise rapidly. Within 6 months, now by October of 2016, his PSA was back up to 76. He also had an elevated alkaline phosphatase, up to 268, and symptoms of increasing fatigue and some back pain. Not surprisingly, he was also noted to have multiple new osseous metastatic disease in his spine and pelvis on scans.

The patient was started on radium-223. His enzalutamide was continued and he was treated with 3 cycles of therapy, after which time his PSA had declined to 31. His alkaline phosphatase went all the way back into the normal range, at 80. His symptoms had improved, with some improvement in his fatigue and stabilization, and his physical activity increased. On scans, we saw stabilization of his metastatic burden.

This case really illustrates one of the spectrum of cases that we see in prostate cancer, and that’s of accelerated disease. This is a patient who presented with some urinary symptoms and palpable, high-volume disease. Only about 15% of prostate cancer patients that are diagnosed each year present with this kind of Gleason 8 to 10 cancer. Not surprisingly, it’s usually associated with an elevated PSA, symptoms, and multiple cores that are positive. These are the patients, at surgery or radiation therapy, that we treat for stage III disease, because, commonly, that’s what they have. It’s not surprising that many of these patients who do undergo surgery end up needing radiation afterwards.

What’s a little unusual in this case is how quickly this patient progressed through primary hormonal therapy as well as secondary hormonal therapy. Not all Gleason 9 cancers will do that, but some do. It suggests that, upfront, this is a disease biology that’s not completely dependent on the androgen access. When I see that kind of case—somebody who, within a couple of years of diagnosis, presents from localized disease to castration-resistant metastatic disease with really short intervals of response to primary hormonal therapy—I’m already thinking, even though I’m going to use my secondary novel hormonal agents, that this is a patient who is going to need a broader array of treatment strategies. These are the patients for whom we also like to do genomic profiling on, to see whether there are other alterations and mutations. Could there be DNA [deoxyribonucleic acid] damage repair pathways or others that we want to target? I’m thinking about my cytotoxic therapies, chemotherapy, and my radiopharmaceutical radium. These are the kinds of therapies that these patients are going to need, that can treat the tumor more indiscriminately than a single pathway.

Transcript edited for clarity.

mCRPC Treated With Radium-223 Therapy

January 2015

H&P:

• A 71-year old gentleman presented with urinary incontinence
• Past medical history: HBP controlled with lisinopril
• On digital rectal examination prostate was enlarged
• Patient was asymptomatic

Imaging:

• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 9 [4+5] with 9 of 12 cores positive
  • PSA, 10.2 ng/mL
• CT scan was negative for metastases
• He was started on a 3-month depot injection of leuprolide 22.5 mg and treated with 7800 cGy IMRT

April 2016

• Patient returned for 3-month injection; his PSA level increased to 47 ng/mL
  • CT/Bone scans were negative for metastases
• He was started on enzalutamide
  • PSA, 12 ng/mL

October 2016

• 6 months later the patient complained of severe fatigue and lower back pain
  • Imaging with CT and bone scan showed multiple metastases of the spine and pelvis
  • PSA levels increased to 76 ng/mL
  • ALP, 268 U/I
• Radium-223 therapy was initiated in addition to continuing enzalutamide
• After 3 infusions of radium-223
  • PSA declined to 31 ng/mL
  • ALP decreased to 80 U/l
  • CT scan showed no new bone metastases
  • Fatigue decreased, and patient’s physical activity increased