What is the best treatment for localized oligometastatic (having a limited number of metastases) metastasis of prostate cancer with a high Decipher (Genomic Classifier) score?

From the Guidelines

For oligometastatic prostate cancer with a high Decipher score, the recommended treatment approach is metastasis-directed therapy (MDT) with stereotactic body radiation therapy (SBRT) to the metastatic lesions, as it has been shown to improve ADT-free survival and delay time to ADT initiation 1.

Treatment Approach

The treatment approach should prioritize controlling the oligometastatic lesions while minimizing toxicity and preserving quality of life.

• MDT with SBRT has been evaluated in several studies, including the STOMP trial, which demonstrated an improvement in ADT-free survival with MDT compared to observation 1.
• The ORIOLE trial also supported the use of MDT with SBRT, showing no significant difference in quality of life scores between the MDT and observation groups 1.

Systemic Therapy

While the evidence for systemic therapy in combination with MDT is limited, the use of androgen deprivation therapy (ADT) with a GnRH agonist or antagonist, such as leuprolide or degarelix, may be considered in patients with high-risk disease or those who have progressed on MDT alone.

• The addition of a novel hormonal agent like abiraterone or enzalutamide may also be considered in patients with high-risk disease or those who have progressed on ADT alone 1.

Monitoring and Follow-up

Regular monitoring with PSA levels every 3 months and imaging (CT and bone scan) every 6-12 months is essential to assess treatment response and detect any signs of disease progression.

• The goal of treatment is to delay disease progression and potentially improve survival by addressing both the oligometastatic lesions directly and suppressing the androgen axis that drives prostate cancer growth.

From the FDA Drug Label

The major efficacy outcome of the study was metastasis-free survival (MFS), defined as the time from randomization to whichever of the following occurred first 1) loco-regional and/or distant radiographic progression per BICR or 2) death up to 112 days after treatment discontinuation without evidence of radiographic progression A statistically significant improvement in MFS and OS was demonstrated in patients randomized to receive XTANDI compared with patients randomized to receive placebo. The primary efficacy outcome was also supported by a statistically significant delay in time to first use of new antineoplastic therapy (TTA) for patients in the XTANDI arm compared to those in the placebo arm.

The best treatment for localized oligometastatic metastasis of prostate cancer with a high Decipher (Genomic Classifier) score is enzalutamide (XTANDI), as it has demonstrated a statistically significant improvement in metastasis-free survival (MFS) and overall survival (OS) compared to placebo 2.

• Key benefits of enzalutamide include:
  • Delay in time to first use of new antineoplastic therapy
  • Improvement in radiographic progression-free survival (rPFS)
  • Improvement in overall survival (OS)

From the Research

Treatment Options for Localized Oligometastatic Prostate Cancer

• Local therapies, including cryoablation, radiation therapy, and cytoreductive prostatectomy, are being increasingly utilized in the treatment of oligometastatic prostate cancer (OMPC) 3, 4, 5.
• Radiation therapy combined with androgen deprivation therapy (ADT) has demonstrated improvements in progression-free survival in clinical trials, such as the STAMPEDE Arm G and HORRAD trials 3, 5.
• Cytoreductive prostatectomy (CRP) combined with ADT has emerged as a potential strategy for managing OMPC, with promising findings from retrospective studies 3, 4, 5.
• Several randomized controlled trials are currently underway to further investigate the role of CRP in the oligometastatic setting 3, 4, 5.

Considerations for Treatment Selection

• Treatment selection for OMPC remains controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making 3, 4, 5.
• The Decipher Genomic Classifier score may be used to guide treatment selection, but its role in determining the best treatment for OMPC is not clearly established in the available evidence.
• Further studies are necessary to identify men with oligometastatic disease who will benefit from local treatment 5.

Emerging Trends and Ongoing Research

• Local therapy of the prostate in the setting of OMPC is a relatively new concept, and ongoing randomized trials are comparing cytoreductive therapy with standard-of-care treatment options 6.
• Stereotactic radiotherapy (RT) of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing OMPC, and may delay the start of ADT 7.
• Ongoing prospective randomized trials will be helpful to evaluate the role of local therapy in OMPC 7.