From the Guidelines
For high-risk prostate cancer classified as cT3aN0M0, the recommended management is multimodal therapy combining external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT), as supported by the most recent guidelines 1.
Key Recommendations
- Patients should receive EBRT to the prostate and seminal vesicles at doses of 76-78 Gy, often with pelvic lymph node irradiation, in combination with long-term ADT (2-3 years) 1.
- Offer patients IMRT/VMAT plus IGRT with 76-78 Gy in combination with long-term ADT (2-3 years) 1.
- Radical prostatectomy with extended pelvic lymph node dissection may be considered as an alternative approach for select patients with good performance status, though adjuvant therapy may still be needed 1.
- The combination of radiation with hormonal therapy has shown superior outcomes in terms of local control, metastasis-free survival, and overall survival compared to single-modality treatment 1.
Rationale
- cT3a disease (extracapsular extension) has a higher risk of progression, making multimodal therapy essential for optimal outcomes 1.
- The guidelines recommend against active surveillance for patients with high-risk localized prostate cancer, and watchful waiting should only be considered in asymptomatic men with limited life expectancy 1.
- Cryosurgery, focal therapy, and HIFU treatments are not recommended for men with high-risk localized prostate cancer outside of a clinical trial 1.
Additional Considerations
- Brachytherapy boost (low dose rate or high dose rate) may be offered to eligible patients receiving EBRT and ADT 1.
- Abiraterone may be considered in combination with ADT and EBRT for patients with high-risk features 1.
- The choice of treatment should be individualized based on patient performance status, life expectancy, and preferences, as well as tumor characteristics and risk factors 1.
From the FDA Drug Label
The major efficacy outcome measure was metastasis-free survival (MFS) in patients randomized to receive XTANDI plus leuprolide compared to patients randomized to receive placebo plus leuprolide MFS was defined as the time from randomization to whichever of the following occurred first 1) radiographic progression per BICR or 2) death. A statistically significant improvement in MFS was demonstrated in patients randomized to receive XTANDI plus leuprolide compared with patients randomized to receive placebo plus leuprolide. A statistically significant improvement in MFS was also demonstrated in patients randomized to receive XTANDI as a single agent compared with patients randomized to receive placebo plus leuprolide
The recommended management for high-risk prostate cancer classified as cT3aN0M0 is hormonal therapy with XTANDI (enzalutamide) plus leuprolide or XTANDI as a single agent, as it has been shown to improve metastasis-free survival (MFS) compared to placebo plus leuprolide 2.
- Key points:
- XTANDI plus leuprolide has been shown to improve MFS in patients with high-risk non-metastatic castration-sensitive prostate cancer (nmCSPC)
- XTANDI as a single agent has also been shown to improve MFS in patients with high-risk nmCSPC
- The improvement in MFS was statistically significant in both cases
- Clinical decision: Based on the available evidence, XTANDI plus leuprolide or XTANDI as a single agent can be considered as a treatment option for patients with high-risk prostate cancer classified as cT3aN0M0 2.
From the Research
Management of High-Risk Prostate Cancer cT3aN0M0
The management of high-risk prostate cancer classified as cT3aN0M0 involves a combination of treatments to control the disease and prevent progression.
- Androgen Deprivation Therapy (ADT): ADT is a key component of treatment for high-risk prostate cancer, as it helps to potentiate irradiation and destroy infraclinical androgen-dependent disease outside the irradiated volume 3.
- Radiotherapy: External beam radiotherapy is used to control pelvic-confined disease, and image-guided intensity-modulated radiotherapy has replaced conventional irradiation, allowing for dose escalation and improved local control without increasing toxicity 3.
- Duration of ADT: The optimal duration of ADT is still being studied, but research suggests that 18 months of ADT may be sufficient for select high-risk patients, potentially reducing the risk of adverse effects without compromising survival or quality of life 4.
- Combination Therapy: Combining ADT with docetaxel and estramustine has been shown to improve relapse-free survival in patients with high-risk localized prostate cancer, although this approach may not be suitable for all patients 5.
- Intense Androgen-Deprivation Therapy: Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate has been studied as a neoadjuvant treatment for localized high-risk prostate cancer, with promising results in terms of reducing tumor burden 6.
- Optimizing ADT with Radiation Therapy: The benefit of ADT in combination with radiation therapy is well established, but the optimal duration and intensity of ADT are still being refined, with a focus on minimizing adverse effects while maintaining survival benefits 7.
Treatment Considerations
When managing high-risk prostate cancer cT3aN0M0, it is essential to consider the individual patient's risk factors, overall health, and potential for adverse effects from treatment. A multidisciplinary approach, involving close cooperation between general practitioners and specialists, can help to tailor the treatment policy and prevent or mitigate adverse effects.