eCase - Prostate Cancer Biomarker Module

Introduction

In this module, Himisha Beltran, MD, and Steven Christopher Smith, MD, PhD, discuss the biologic rationale for targeting homologous recombination repair (HRR) mutations, optimal testing for actionable HRR mutations in patients with metastatic prostate cancer, and using test results to individualize PARP inhibitor–based therapy.

The key points discussed in this module are illustrated with thumbnails from the accompanying downloadable PowerPoint slideset, which can be found here or downloaded by clicking any of the slide thumbnails alongside the expert commentary.

Clinical Care Options plans to measure the educational impact of this activity. Some questions will be asked twice: once at the beginning of the activity and once again after the discussion that informs the best choice. Your responses will be aggregated for analysis, and your specific responses will not be shared.

Before continuing with this educational activity, please take a moment to answer the following questions.

For those providing patient care, how many patients with prostate cancer do you provide care for in a typical month?

A.
1-5
B.
6-10
C.
11-15
D.
16-20
E.
>20

In which of the following clinical settings do expert and clinical guidelines unconditionally recommend BOTH germline and somatic/tumor testing, including HRR gene alterations, for patients with prostate cancer?

A.
Low risk and very low risk organ confined prostate cancer
B.
Favorable intermediate-risk prostate cancer
C.
Intermediate-risk prostate cancer and family history of cancer
D.
All metastatic prostate cancer, whether castration naive or resistant

A 64-year-old White man with metastatic CRPC to the bone experienced disease progression on abiraterone acetate plus prednisone (AAP) with progressing metastases and an epidural mass with spinal cord compression. He underwent a procedure to mitigate the significant risk of paralysis, which afforded the opportunity for somatic sampling and molecular profiling. Pathology showed no evidence of neuroendocrine transformation. Comprehensive genomic profiling revealed a deleterious BRCA2 variant.

Of the following options, which therapy would you recommend as the appropriate next-line treatment option for this patient with BRCA2-mutated metastatic CRPC?

A.
Cabazitaxel
B.
Enzalutamide
C.
Olaparib
D.
Lu-PSMA-617

A 57-year-old Black man underwent a prostatectomy and early salvage radiotherapy for high-stage, locally advanced prostate cancer 6 years ago. When the patient reestablished care after sporadic follow-up during the COVID-19 pandemic, he was asymptomatic, but his prostate-specific antigen (PSA) had climbed to 283 ng/mL. Scans demonstrated innumerable bone and lymph node metastases. After a period of androgen-deprivation therapy (ADT) alone, he presented with progressive lymphadenopathy and rapid growth of a supraclavicular lymph node. Pathology of the lymph node confirmed a prostatic lineage and ruled out neuroendocrine transformation. Biomarker testing identified a BRCA2 frameshift mutation.

In your practice, which of the following treatment options would you recommend for this patient with BRCA2-mutated metastatic CRPC?

A.
AR pathway inhibitor therapy (ie, enzalutamide or abiraterone)
B.
Lu-PSMA-617
C.
PARP inhibitor therapy (ie, rucaparib or olaparib)
D.
PARP inhibitor plus AR pathway inhibitor (ie, niraparib plus AAP, olaparib plus AAP, or talazoparib plus enzalutamide)

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Biomarker Testing in Prostate Cancer: An Essential Component in Transforming Care

Himisha Beltran, MD

Steven Christopher Smith, MD, PhD

Activity

Introduction

For those providing patient care, how many patients with prostate cancer do you provide care for in a typical month?

In which of the following clinical settings do expert and clinical guidelines unconditionally recommend BOTH germline and somatic/tumor testing, including HRR gene alterations, for patients with prostate cancer?

Of the following options, which therapy would you recommend as the appropriate next-line treatment option for this patient with BRCA2-mutated metastatic CRPC?

In your practice, which of the following treatment options would you recommend for this patient with BRCA2-mutated metastatic CRPC?