Case Overview: 82-Year-Old Man With Metastatic CRPC

Matthew R. Smith, MD, PhD, presents the case of a 82-year-old man with metastatic castration-resistant prostate cancer (mCRPC) and shares his initial impressions.

Matthew R. Smith, MD, PhD: Hello. I'm Dr Matthew Smith, a medical oncologist and the director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center. I'll be presenting a case of advanced-stage prostate cancer and newer data about the optimal management of this patient. The case is an 82-year-old man who presents to a urologist with nocturia. His digital rectal examination was abnormal and PSA [prostate-specific antigen] was elevated at 31 ng/mL. He has no family history of prostate cancer. His past medical history is notable for diabetes and hypertension. He has some complications related to his diabetes, including neuropathy, and he often uses a cane when he's walking long distances. He undergoes prostate biopsies that demonstrate extensive prostate cancer; Gleason [grade] 4+4. Then he has imaging bone scan shows no detectable spread to bone. Abdominal pelvic CT scan shows multiple enlarged pelvic and retroperitoneal nodes consistent with metastatic prostate cancer. He began continuous androgen deprivation therapy in October 2016. His PSA declines to undetectable after 3 months and remains so after 1 year. He has a repeated abdominal pelvic CT after completing a year of therapy and that shows resolution of the previously noted pelvic and retroperitoneal nodes.

By April 2018, his PSA is rising. The latest value is 2.7 ng/ML; his estimated PSA doubling time is about 6 months. He undergoes conventional imaging with bone scan and CT that demonstrate no detectable prostate cancer. He then has a PSMA [prostate-specific membrane antigen] PET [positronemission tomography scan that shows multiple areas of increased uptake in the pelvis and retroperitoneum consistent with previously identified sites of metastases. Laboratory testing is otherwise unrevealing. He was prescribed enzalutamide and began that treatment. His PSA declined, although he discontinued treatment on his own because of unacceptable fatigue. He also complained about some instability of his gait. After observing him for a few months off treatment, the symptoms resolved and the decision was made to treat him with darolutamide and continue androgen deprivation therapy with leuprolide depot. His PSA declined to undetectable, and there's been no need for dose reductions or treatment interruptions in his therapy.

This case represents a quite familiar and common presentation of de novo metastatic disease. In this case, a patient with a lower burden of metastases with a substantial size primary tumor, high Gleason grade, and metastases to pelvic and retroperitoneal nodes. He had a nice response to primary androgen deprivation therapy, but as expected, ultimately progressed to castration-resistant disease with the rising PSA. In current clinical practice, we might've considered intensification of systemic treatment at the time of his initial presentation, but when he was first diagnosed that data did not exist, so the decision was made to treat him with primary androgen deprivation therapy.

Transcript edited for clarity.

Case: A 82-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer

Sept. 2016

Initial presentation

  • A 82-year-old man with nocturia

Clinical workup

  • Abnormal digital rectal exam, PSA 31 ng/mL
  • No family history of prostate cancer
  • Diabetes and hypertension, both of which are managed with medications, neuropathy and uses a cane for long distances
  • Prostate biopsy confirms advanced adenocarcinoma of the prostate and Gleason score of 8 (4 + 4)
  • Bone scans show no detectable spread to bone, abdominal pelvic CT scan shows enlarged pelvic and retroperitoneal nodes consistent with metastatic prostate cancer.
  • His ECOG PS is 1


  • Patient starts continuous ADT in October 2016.
  • PSA levels go down to undetectable levels within 3 months after start of treatment. Levels are checked every 3 months thereafter.
  • Patient undergoes repeat abdominal pelvic CT scan after completing a year of therapy which show resolution of pelvic and retroperitoneal nodes.

April 2018

  • An increase in PSA is seen and PSA levels are 2.7 ng/ml, with PSA doubling time of 6 months
  • Patient undergoes conventional imaging with bone scan and CT that show no detectable prostate cancer.
  • PSMA PET scan shows multiple areas of increased uptake in pelvis and retroperitoneum, consistent with previously identified sites of metastasis.
  • Lab tests are normal and patient has adequate liver, renal and bone marrow function.
  • Patient is treated with enzalutamide (160 mg/day) and PSA levels decline
  • After some time on enzalutamide, patient decides to discontinue treatment due to fatigue and problems with gait.
  • Symptoms resolve on their own after going off treatment for a few months
  • Patient is started on darolutamide and continued ADT (leuprolide depot) and remains on this treatment
  • PSA levels stay undetectable on treatment
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