Metastatic Hormone-Sensitive Prostate Cancer Progression to CRPC - Episode 1

Case of mHSPCa Progressing to mCRPC

May 17, 2019

Jorge Garcia, MD:This is the case of a 64-year-old [man] who was referred to medical oncology complaining of lower-back pain. Part of his initial work-up included a PSA [prostate-specific antigen test], which was found to be elevated at 79.5. His initial imaging studies included a technetium [Tc] 99 m bone scan and a CT [computed tomography] scan of the chest, abdomen, and pelvic region. He was found not to have any evidence of metastases in the visceral organs and/or lymphadenopathy. However, his bone scan did demonstrate the presence of 3 areas of bone metastasis: 1 in the right pelvic area and 2 in the lumbar spine. His transrectal ultrasound with multiple prostate biopsies demonstrated the presence of adenocarcinoma of the prostate with a Gleason score of 9: 5+4. Part of his past medical history includes hypertension and hyperlipidemia, for which both were well controlled on oral medications. He also has a family history of colorectal cancer. His Karnofsky Performance Status at presentation was 90%, and at physical exam he was completely unremarkable.

At that time, the patient was deemed to be metastatic, specifically with de novo high-volume metastatic prostate cancer. The decision was for him to initiate systemic therapy with testosterone suppression using an LHRH [luteinizing hormone-releasing hormone] agonist, and abiraterone acetate and prednisone. Initially, after he started therapy, he had a very good serological response and his PSA nadir at 6 months was 0.9 ng/mL. Some of his adverse effects during therapy included fatigue, hot flashes, and muscle aches, which are typical adverse effects from a lack of testosterone.

In 2017, despite of his testosterone suppression—his testosterone was less than 50 at the time—he developed serological suppression. His PSA in August was 1.56. A subsequent PSA in November was 4.4. However, the patient at the time was completely asymptomatic. Later on, in February 2018, the patient began complaining of lower-back pain again. He had left pelvic discomfort—specifically, it radiated to the right hip area—and he was taking, at the time, over-the-counter pain medications, specifically NSAIDs [nonsteroidal anti-inflammatory drugs]. His PSA at the time was 6.5, so it was decided for him to undergo a new imaging scan. His whole-body bone scan and his CT scan of the chest, abdomen, and pelvic region demonstrated the presence of 2 new lesions, 1 of which was in the lumbar spine. However, there was no evidence of epidural disease or fractures and no evidence of visceral disease.

The patient then was diagnosed with minimally symptomatic metastatic castration-resistant prostate cancer. At the time, the decision was for him to discontinue abiraterone acetate and prednisone, and he moved on to radium 223 [dichloride]. He completed 6 cycles of radium 223 on a monthly basis. He did have some improvement of his bone discomfort. But he did have, however, have some adverse effects, including fatigue and anemia. His PSA level during therapy ranged from 6.5 to 8.9, but again, the patient was completely asymptomatic.

Later on, in September 2018, the patient started to experience some anorexia, fatigue, and progressive abdominal pain. Again, new imaging studies were completed. A technetium [Tc] 99 m bone scan demonstrated stability of disease in his bony metastases. However, his CT scan of the chest, abdomen, and pelvic region now unfortunately demonstrated progressive disease, specifically with new liver metastases. His PSA level at that time was 10.7, so not a lot of PSA for the amount of disease that he had in his scans. His hemoglobin level at the time was 10 [g/dL]. His ANC [absolute neutrophil count] was 3900, and his platelet count was normal, at 331,000. He had normal liver function tests including ALT [alanine transaminase], AST [aspartate transaminase]. His alkaline phosphatase and his bilirubin were also normal. His LDH [lactate dehydrogenase count], however, was elevated—at 565.

At the time, the decision was for the patient to initiate docetaxel-based chemotherapy, and he was placed on the standard dosage of 75 mg/m2on a 21-day cycle. The patient completed 6 cycles of therapy with some of the expected adverse effects from therapy, including fatigue, alopecia, and some evidence of peripheral neuropathy. His scans at the completion of his 6 cycles of chemotherapy did demonstrate the presence of stability of disease, specifically RECIST-defined stable disease. He did have some decrease in tumor burden in his liver metastases. His hemoglobin level, at the time of completion of chemotherapy, was around 12.1, and his ANC and platelet levels were within normal limits.

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.