Metastatic Hormone-Sensitive Prostate Cancer Progression to CRPC - Episode 4

Diagnosing Bone Mets in Prostate Cancer

May 17, 2019

Jorge Garcia, MD:We have prostate cancer screening in North America. Although it is a controversial topic right now in the field, I think most men in the United States do walk with what we call localized or locally advanced disease. These are patients who have no evidence of metastases, which means that it allows you—as a consumer, as a patient—to be able to achieve cure with either surgery or radiation therapy, or the combination of those 2, for that matter.

However, there is a small pocket of patients who are walking in the office with de novo disease, which means they have their primary prostate in place, and they just simply presented like this patient with symptomatic disease. They have back pain, they’re a man older in age, and they have symptoms that will raise the suspicion of, “Well, maybe they have prostate cancer.” So in this particular case, the patient presented with back pain. That prompted the medical team to actually do a work-up that included a PSA [prostate-specific antigen test], which was found to be quite elevated—around 79 or so. And that prompted them to actually have the patient undergo imaging scans, traditionally including a bone scan and a CT [computed tomography] scan of the chest, abdomen, and pelvic region. And those scans for this patient, unfortunately, were able to show that the patient had developed prostate cancer metastases in bony structures.

Obviously, prostate cancer is a bone-tropic tumor, which means that 80% to 90% of men who develop advanced prostate cancer will develop metastases in bony areas, meaning bony metastases. Half of them will have lymph node disease, which is either pelvic lymphadenopathy or perhaps peritoneal lymphadenopathy in the back of the abdomen. A small percentage of patients, maybe around 20% to 25%, depending how you look at the data, may present with visceral metastases, which is defined by the presence of liver disease and/or lung disease, which is not quite common for us in prostate cancer. If you develop prostate cancer metastases, we do know not only that you have developed advanced prostate cancer and have developed metastatic disease, but the impact of developing bone metastasis in a male with prostate cancer affects their mortality. Within 5 years, prior to novel oral agents getting approved, less than 5% of people would actually be alive within 5 years when they had developed metastatic disease to the bone.

Now, with so many of the changes in the field—oral novel therapy, immunotherapy, radionucleotide-based approaches, chemotherapy, for that matter, and the sequential options for these patients who receive these treatments over time throughout the natural history of their prostate cancer—I think those numbers have improved from less than 5% to around 30%, which still tells you that if you develop bony metastatic disease, almost 80% of patients will die within 5 years. In fact, the best data that we have looking at STAMPEDE, which are the British data looking at chemotherapy and abiraterone, LATITUDE looking at abiraterone, and even our own American data looking at CHAARTED, we know that men with high-volume disease, if they get suppression of testosterone alone, have a median survival of around 34 to 36.5 months.

On the contrary, if you add or intensify their therapy, suppress their testosterone, and then intensify with chemotherapy, for that matter, or if you decide to use abiraterone acetate, you can actually get that median survival to almost 55, almost 60 months or so, which is a significant improvement in outcome.

Transcript edited for clarity.


Case: Met HSPCa Progressing to mCRPC

June 2016

H&P

  • A 64-year old gentleman referred to a medical oncologist with lower back pain
  • Initial work-up included:
    • PSA of 79.5 ng/ml
    • WBS showing 3 bone metastasis — 1 Right pelvic area and 2 in lumbar spine
    • CT Chest/Abdomen and Pelvis showed no pelvic lymph nodes and no evidence of visceral disease
    • TRUS/Bx revealed adenocarcinoma of the prostate gland with a Gleason score of 9 [5+4]
  • PMH: HTN, Hyperlipidemia - both controlled on oral medications and a family history of colon cancer
  • His KPS is 90% and the remaining of his blood work is unremarkable

Pt was started on ADT with LHRH agonist-based therapy and abiraterone + prednisone. He also was placed on monthly zoledronic acid.

  • During therapy minimal AEs that included G1 fatigue, hot flashes and muscle aches
  • Nadir PSA at 6 months was 0.9 ng/mL

August 2017

  • Despite a Testosterone level < 50 ng/dL, patients PSA began to rise
    • PSA August 1.56 ng/mL
    • PSA November 4.4 ng/mL
    • Patient remain completely asymptomatic

February 2018

  • Patient is complaining of new back pain (L spine radiating to right hip area) for which he takes over the counter NSAIDs
  • PSA now is 6.5ng/mL
  • Repeat WBS and CT C/A/P demonstrated 2 new lesions in L spine. No epidural disease or fractures and no evidence of visceral disease.
  • Patient is diagnosed as minimally symptomatic Metastatic castration-resistant and abiraterone + prednisone was discontinued.
  • Radium 223 therapy was initiated — 6 cycles were completed with improvement of bone pain and minimal AEs that included G1 fatigue and G1 anemia.
    • PSA during therapy ranged from 6.5 to 8.9ng/mL

September 2018

  • Patient now is experiencing anorexia, fatigue and progressive abdominal pain
  • WBS showed stable disease however CT C/A/P now showed progressive liver metastases
  • PSA is now 10.7 ng/ml
  • Hemoglobin is 10 g/dL, ANC is 3900 and Platelets are 331,000
  • Normal Liver function tests (ALT/AST, Alk Phos, TBili) and LDH of 565

Patients is started on Docetaxel-based chemotherapy (75mg/m2 on 21-day cycles)

Patient completes 6 cycles of therapy with expected AEs including G1 fatigue, G1 alopecia and G1 peripheral neuropathy. His scans at the completion of chemotherapy showed SD with tumor burden reduction in liver lesions and SD in bones. His Hemoglobin level at the completion of chemotherapy is 12.1 g/dL and his ANC and platelets are also within normal limits.