From the Guidelines
For castration-sensitive prostate cancer with PSMA expression and low PSA levels, the recommended treatment approach is androgen deprivation therapy (ADT) combined with either docetaxel chemotherapy or novel hormonal agents such as abiraterone acetate, enzalutamide, apalutamide, or darolutamide. This approach is based on the most recent guidelines from the National Comprehensive Cancer Network (NCCN) 1. The use of ADT monotherapy is discouraged unless there are clear contraindications to combination therapy.
Treatment Options
- ADT typically involves a GnRH agonist (like leuprolide 7.5mg monthly or 22.5mg every 3 months) or antagonist (like degarelix 240mg initial dose, then 80mg monthly).
- For combination therapy, docetaxel is typically administered at 75mg/m² every 3 weeks for 6 cycles alongside ADT.
- Abiraterone is given at 1000mg daily with prednisone 5mg twice daily.
- Enzalutamide (160mg daily), apalutamide (240mg daily), or darolutamide (600mg twice daily) can also be combined with ADT.
Treatment Selection and Monitoring
Treatment selection should be individualized based on disease volume, metastatic burden, comorbidities, and patient preference. Regular monitoring of PSA levels, imaging, and side effects is essential. This approach is recommended because these combinations have demonstrated improved overall survival compared to ADT alone, even in patients with discordant PSMA expression and PSA levels 1. The presence of PSMA expression may also indicate potential future candidacy for PSMA-targeted therapies if the disease becomes castration-resistant.
Key Considerations
- The NCCN guidelines emphasize a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects 1.
- The optimal level of serum testosterone decline has yet to be defined, but achieving adequate suppression of serum testosterone (<50 ng/dL) with medical or surgical castration is crucial 1.
From the FDA Drug Label
The major efficacy outcome measure was radiographic progression-free survival (rPFS) based on blinded independent central review (BICR) Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. XTANDI demonstrated a statistically significant improvement in rPFS and OS compared to placebo.
The recommended treatment approach for castration-sensitive prostate cancer that generates Prostate-Specific Membrane Antigen (PSMA) with low levels of Prostate-Specific Antigen (PSA) is enzalutamide (XTANDI), as it has shown a statistically significant improvement in radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo 2.
- Key points:
- XTANDI has demonstrated efficacy in patients with castration-sensitive prostate cancer
- The treatment has shown improvement in rPFS and OS compared to placebo
- XTANDI can be considered as a treatment option for patients with castration-sensitive prostate cancer, regardless of PSMA or PSA levels.
From the Research
Treatment Approach for Castration-Sensitive Prostate Cancer
- The recommended treatment approach for castration-sensitive prostate cancer that generates Prostate-Specific Membrane Antigen (PSMA) with low levels of Prostate-Specific Antigen (PSA) involves androgen-deprivation therapy (ADT) as the mainstay of treatment 3.
- However, due to the disease's heterogeneity and limited duration of response to ADT, combinations of ADT plus chemotherapy or novel hormonal therapies are being tested with promising results 3, 4.
- Novel hormonal therapies such as abiraterone, enzalutamide, and apalutamide have been approved for upfront intensification in addition to ADT for metastatic castration-sensitive prostate cancer (mCSPC) 4.
- For patients with oligometastatic hormone-sensitive prostate cancer, metastases-directed therapy with radioligand therapy (RLT) using 177Lu-PSMA has shown potential in prolonging progression-free survival and postponing the need for ADT 5.
Role of PSMA and PSA in Treatment
- PSMA is a promising target for therapy in prostate cancer, and its expression can be used to guide treatment decisions 5.
- Low levels of PSA do not necessarily preclude the use of PSMA-targeted therapies, as PSMA expression can be independent of PSA levels 5.
- Further research is needed to fully understand the relationship between PSMA and PSA expression in prostate cancer and to develop effective treatment strategies for patients with low PSA levels 6.
Future Directions
- Personalized medicine, including molecular testing and precision medicine approaches, may play a key role in optimizing treatment decisions for patients with castration-sensitive prostate cancer 7.
- Ongoing clinical trials are investigating the clinical value of more intensified treatments, including combinations of multiple effective treatments, and novel therapies such as immunotherapeutics and precision medicine approaches 7.