Nomogram predicting the outcome of salvage radiation therapy for prostate-specific antigen failure following radical prostatectomy: an exploratory analysis of a randomized, multicenter, open-label, phase 3 trial (JCOG0401) | International Journal of Clinical Oncology

Nomograms: Tools to Predict Treatment Success
Research Shows Salvage Radiation Therapy Benefits for PSA Failure After Prostatectomy

For the many men in our support group who have experienced rising PSA levels after a radical prostatectomy, deciding on the next treatment step can be challenging. Recent research from Japan offers new guidance on treatment options, with important implications for patients considering salvage radiation therapy (SRT).

JCOG0401 Trial Shows Benefits of Early Salvage Radiation

A randomized, multicenter, phase 3 clinical trial conducted in Japan (JCOG0401) has demonstrated that salvage radiation therapy is more effective than hormone therapy alone for men experiencing PSA failure after radical prostatectomy.

The study, which included patients whose PSA had initially decreased to <0.1 ng/ml after surgery but then increased to 0.4-1.0 ng/ml, found that initiating salvage radiation therapy led to significantly longer time to treatment failure compared to starting with hormone therapy alone.

Patients who received radiation therapy had a median time to treatment failure of 8.6 years compared to 5.6 years for those receiving only hormone therapy. This strongly suggests that for appropriate candidates, SRT should be considered before moving directly to hormone therapy.

Nomograms: Tools to Predict Treatment Success

A key development in this field has been the creation of nomograms - statistical prediction tools that help doctors and patients estimate the likelihood of treatment success. These tools use multiple factors from your specific case to calculate personalized outcome predictions.

The salvage radiation therapy nomogram developed at Memorial Sloan Kettering Cancer Center (MSKCC) calculates the probability that cancer will be controlled and PSA levels will remain undetectable six years after salvage therapy. This tool has been widely used to help patients and their doctors make informed decisions about pursuing SRT.

A more recent nomogram update from Cleveland Clinic provides additional predictive capabilities. This updated multi-institutional tool was developed to provide more accurate predictions in the current era of earlier intervention. The Cleveland Clinic nomogram can be accessed online and provides estimates for both 5-year and 10-year freedom from biochemical failure.

Key Factors That Influence SRT Success

Research has identified several factors that significantly impact the success of salvage radiation therapy:

  1. PSA Level at Treatment: Patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower showed a 48% disease-free rate at 6 years. Lower PSA levels at the time of SRT correlate with better outcomes.
  2. Gleason Score: Higher Gleason scores from the original prostatectomy are associated with lower success rates for SRT.
  3. PSA Doubling Time: A PSA doubling time of less than 6 months appears to be a strong predictor of outcomes, including prostate cancer-specific mortality. Faster PSA rises generally indicate more aggressive disease.
  4. Surgical Margins: Positive surgical margins (cancer cells at the edge of the removed tissue) are associated with better response to SRT, as this may indicate the cancer is more likely to be localized.
  5. Radiation Dose: Some evidence suggests higher radiation doses may improve outcomes, though this must be balanced against potential side effects.

When to Consider Salvage Radiation Therapy

The available evidence suggests that SRT is most effective when initiated early, at the first sign of biochemical recurrence. According to specialists, "nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence."

For men in our support group considering their options after PSA failure, these nomograms can provide valuable information to discuss with your treatment team. They may help determine whether you are likely to benefit from salvage radiation therapy or whether other approaches should be considered.

Looking Ahead: Newer Developments

Recent advances include the integration of PSMA PET/CT imaging to better guide salvage radiation treatment decisions. Researchers have developed nomograms that incorporate PSMA PET findings to predict outcomes for patients receiving salvage radiation therapy. This represents an important step forward in personalizing treatment plans.

Additionally, ongoing research is investigating the optimal timing of hormone therapy in conjunction with SRT, as well as the potential benefits of treating the pelvic lymph nodes in addition to the prostate bed.

References

  1. Yokomizo A, Wakabayashi M, Satoh T, et al. Salvage Radiotherapy Versus Hormone Therapy for Prostate-specific Antigen Failure After Radical Prostatectomy: A Randomised, Multicentre, Open-label, Phase 3 Trial (JCOG0401). European Urology. 2020;77(6):689-698. https://pubmed.ncbi.nlm.nih.gov/31866092/
  2. Stephenson AJ, Scardino PT, Kattan MW, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. Journal of Clinical Oncology. 2007;25(15):2035-41. https://pubmed.ncbi.nlm.nih.gov/17513807/
  3. Memorial Sloan Kettering Cancer Center. Prostate Cancer Nomograms: Salvage Radiation Therapy. https://www.mskcc.org/nomograms/prostate/salvage_radiation_therapy
  4. Tendulkar RD, Agrawal S, Gao T, et al. Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy. Journal of Clinical Oncology. 2016;34(30):3648-3654. https://ascopubs.org/doi/10.1200/JCO.2016.67.9647
  5. Cleveland Clinic. Prostate Cancer - Predicting PSA Recurrence Following Salvage Radiation Therapy. https://riskcalc.org/ProstateCancerAfterRadicalProstatectomyNew/
  6. Pijpers J, Meeuwis C, Kelder J, et al. Development and Internal Validation of a Novel Nomogram Predicting the Outcome of Salvage Radiation Therapy for Biochemical Recurrence after Radical Prostatectomy in Patients without Metastases on Restaging Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography. European Urology Focus. 2024. https://www.sciencedirect.com/science/article/pii/S2666168324002192
  7. Sandler H, et al. Salvage Radiotherapy Called a Viable Option for Recurrent Prostate Cancer. Renal and Urology News. 2020. https://www.renalandurologynews.com/home/news/urology/prostate-cancer/salvage-radiotherapy-called-a-viable-option-for-recurrent-prostate-cancer/
  8. Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET–Based Salvage Radiotherapy for Recurrent Prostate Cancer. JAMA Network Open. 2023. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2805173

Disclaimer: This article is provided for educational purposes only and does not constitute medical advice. Please consult with your healthcare provider about your specific situation before making treatment decisions.

Nomogram predicting the outcome of salvage radiation therapy for prostate-specific antigen failure following radical prostatectomy: an exploratory analysis of a randomized, multicenter, open-label, phase 3 trial (JCOG0401) | International Journal of Clinical Oncology

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