Modern Radiation Therapy and ADT for High-risk Prostate Cancer Result in Improved Survival

Modern Radiation Therapy and ADT for High-risk Prostate Cancer Result in Improved Survival

Abstract & Commentary

By Samir Kanani, MD

Associate Clinical Professor of Neurosurgery and Radiation Oncology, George Washington University, Radiation Oncology, Inova Fairfax Hospital, Falls Church, VA

Dr. Kanani reports no financial relationships relevant to this field of study.

SYNOPSIS:Historically, men with high risk prostate cancer were believed to have low survival rates after definitive treatment with either surgery or radiation. However, long-term results of dose-escalated radiotherapy of doses ≥ 75.6 Gy, along with long-term androgen deprivation therapy (ADT), demonstrate 5-year survival rate of 92%, 5-year biochemical control rate of 82%, and symptomatic local failure rate of 0%. Death from prostate cancer was only 5.5% at 10 years in men treated with high-dose radiation therapy and ADT.

SOURCE:Nguyen Q, et al. Long-term outcomes for men with high-risk prostate cancer treated definitively with external beam radiotherapy with or without androgen deprivation. Cancer 2013;119:3265-3271.

Historically, disease-free survival rates have been disappointing with external beam radiotherapy alone. Over the last 30 years, significant technological improvements in the delivery of radiotherapy have resulted in the successful and safe delivery of escalating doses. In addition, studies in the 1990s demonstrated improvement in outcomes with long-term androgen deprivation therapy (ADT) in high-risk prostate cancer patients. This led to the hypothesis that the combination of long-term ADT and dose-escalated radiotherapy would likely produce at least an additive effect.

To address the question of whether high doses of radiotherapy combined with long-term ADT results in improved outcomes, Nguyen and colleagues performed a retrospective analysis of 741 men with high-risk prostate cancer treated at M.D. Anderson Cancer Center between 1987 and 2004. High-risk disease was defined as T3 disease, Gleason score 8-10, or PSA > 20 ng/mL. Patients were typically staged with CT scans and bone scans. The median PSA for the cohort was 15.6 ng/mL and the median age was 68 years old. Three hundred seventy-five men were treated with low-dose radiation defined as < 75.6 Gy, 122 men were treated with ADT and low-dose radiation therapy, 71 men were treated with high-dose radiation therapy without ADT, and 173 men were treated with ADT and high-dose radiotherapy (> 75.6 Gy). ADT was started 2 months prior to radiotherapy and continued for a median of 2.9 years. The target for radiotherapy was the prostate and the seminal vesicles and did not include the pelvic lymph nodes.

Compared with low-dose radiotherapy alone, ADT combined with high-dose radiation therapy resulted in improved 5-year overall survival (82% vs 92%), 5-year prostate cancer survival (93% vs 96%), and 5-year clinical failure-free survival (67% vs 92%). There were no local failures in men treated with ADT and high-dose radiotherapy. The 10-year symptomatic local failure rate was only 2% for all patients. High-dose radiotherapy resulted in a 5% absolute benefit in 5-year survival either with or without ADT. Prostate cancer specific deaths were rare among all cohorts at 5.5% at 10 years. The use of ADT improved local failure rates, overall survival rates, and biochemical control.

COMMENTARY

High-risk prostate cancer represents between 13% and 21% of newly diagnosed patients.1 A number of randomized trials done in the United States including RTOG 92-02 have demonstrated improved overall survival in patients with high-risk prostate cancer treated with long-term hormones and radiation compared to short-term hormones and radiation.2 These trials have essentially outlined the standard of care for the last decade in the management of high-risk prostate cancer. Many of these trials including RTOG 92-02 used lower doses of radiation therapy (65-70 Gy). Several trials have demonstrated a benefit to a higher dose of radiation therapy in high-risk patients, which results in improved outcomes when compared to lower doses.3

So what have I learned from this trial as a radiation oncologist who treats prostate cancer patients? Every radiation oncologist is likely already giving dose of at least 75.6 Gy using Intensity Modulated Radiation Therapy (IMRT), so my radiation dose will likely remain unchanged. However, the debate as to what areas need to be irradiated continues to rage on. It is very interesting in this study that there were no local failures in men treated to only the prostate and seminal vesicles. Many radiation oncologists continue to treat the pelvic nodes as well as the prostate and seminal vesicles based on other RTOG trials demonstrating a small benefit early on in progression-free survival.4 There are still questions remaining to be answered. Should men with high-risk prostate cancer be offered surgery when the risk of prostate cancer mortality is < 5% even in high-risk populations or should the standard of care be radiation and hormones? What about the use of combination external beam radiation and brachytherapy? In my opinion, it’s hard to argue against the combination of hormones and high-dose modern radiation therapy in this high-risk population with such excellent results. The alternative is a prostatectomy with a high likelihood of requiring postoperative radiation therapy because of positive margins or extracapsular penetration. Why treat with two treatment modalities when you can treat with one?

References

1. Mettlin CJ, et al. Cancer 1998;83:1679-1684.
2. Horwitz EM, et al. J Clin Oncol 2008;26:2497-2504.
3. Kuban DA, et al. Int J Radiat Oncol Biol Phys 2011;79:1310-1317.
4. Lawton CA, et al. Int J Radiat Oncol Biol Phys 2007;69:646-655.