Adjuvant vs. Salvage Radiation Therapy after Radical Prostatectomy: Role of Decipher® in the Era of Personalized Medicine - Beyond the Abstract

Prostate cancer (PCa) is an important subject in global health, with increasing incidence and burden.1 Radical prostatectomy (RP) is the treatment of choice for many patients. However, some cases experience biochemical recurrence (BCR). According to current guidelines, adjuvant radiation therapy (ART) is administered to reduce the risk of BCR in patients with adverse pathological features (i.e., locally advanced disease or positive margin). An alternative approach is to start radiation therapy after BCR (salvage radiation therapy [SRT]). Although SRT offers a rest and recovery period for the genitourinary system, it might lead to undertreatment and increased risk of metastatic disease. It is unclear which approach is more beneficial for patients with high-risk pathological features. In the era of personalized medicine, a molecular diagnosis has the potential to distinguish patients with a higher risk of progression and metastasis who may benefit from ART.


Decipher® is a genomic test designed to predict the risk of metastasis in patients who have undergone RP. It has been shown that Decipher® is a reliable predictor of metastasis, recurrence, and mortality. As an example, 5-year disease-related mortality in patients with low-risk and high-risk Decipher® were 0% and 9.4%, respectively.2 In another study, the recurrence rate was only 2.6% among patients with low-risk Decipher® scores, while 13.6% of patients with high-risk scores experienced recurrence 10 years following RP.3

We believe that risk stratification based on Decipher® score may determine the best protocol for radiation therapy after RP. One study utilized Decipher® in predicting the risk of adverse pathology in favorable intermediate-risk (FIR) men. The results indicated that patients with high-risk Decipher® scores are almost seven times more likely to harbor adverse pathological features.4 Another group of researchers compared 5-year rate of metastasis in patients who underwent SRT vs. ART and found that ART reduced metastasis in Decipher®’s intermediate- and high-risk groups but not in the low-risk group.5

Decipher® is more expensive than usual care; however, taking quality-adjusted life years (QALY) into account, it seems to be a cost-effective tool to determine the appropriate treatment following RP.6

Decipher® is a promising modality in PCa and in combination with histopathological findings,7 has the potential to further improve the accuracy of the test in clinical decision making.

Written by: Ali Nowroozi, Amirali Karimi, Sanam Alilou, Erfan Amini

Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran. ., Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran. ., Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran. ., Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran. .

References:

  1. Pishgar, Farhad, Hedyeh Ebrahimi, Sahar Saeedi Moghaddam, Christina Fitzmaurice, and Erfan Amini. "Global, regional and national burden of prostate cancer, 1990 to 2015: results from the global burden of disease study 2015." The Journal of urology 199, no. 5 (2018): 1224-1232.
  2. Nguyen, Paul L., Heesun Shin, Kasra Yousefi, Darby J. Thompson, John Hornberger, Andrew S. Hyatt, Ketan K. Badani, Todd M. Morgan, and Felix Y. Feng. "Impact of a genomic classifier of metastatic risk on postprostatectomy treatment recommendations by radiation oncologists and urologists." Urology 86, no. 1 (2015): 35-40.
  3. Glass, Andrew G., Michael C. Leo, Zaid Haddad, Kasra Yousefi, Marguerite du Plessis, Chuhe Chen, Voleak Choeurng et al. "Validation of a genomic classifier for predicting post-prostatectomy recurrence in a community based health care setting." The Journal of urology 195, no. 6 (2016): 1748-1753.
  4. Herlemann, Annika, Huei-Chung Huang, Ridwan Alam, Jeffery J. Tosoian, Hyung L. Kim, Eric A. Klein, Jeffry P. Simko et al. "Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance." Prostate cancer and prostatic diseases 23, no. 1 (2020): 136-143.
  5. Den, Robert B., Kasra Yousefi, Edouard J. Trabulsi, Firas Abdollah, Voleak Choeurng, Felix Y. Feng, Adam P. Dicker et al. "Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy." Journal of Clinical Oncology 33, no. 8 (2015): 944.
  6. Lobo, Jennifer M., Daniel M. Trifiletti, Vanessa N. Sturz, Adam P. Dicker, Christine Buerki, Elai Davicioni, Matthew R. Cooperberg et al. "Cost-effectiveness of the Decipher genomic classifier to guide individualized decisions for early radiation therapy after prostatectomy for prostate cancer." Clinical genitourinary cancer 15, no. 3 (2017): e299-e309.
  7. Dalela, Deepansh, María Santiago-Jiménez, Kasra Yousefi, R. Jeffrey Karnes, Ashley E. Ross, Robert B. Den, Stephen J. Freedland et al. "Genomic classifier augments the role of pathological features in identifying optimal candidates for adjuvant radiation therapy in patients with prostate cancer: development and internal validation of a multivariable prognostic model." Journal of Clinical Oncology 35, no. 18 (2017): 1982.
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