Article Tools
Correspondence
Article Tools
Early Treatment Gets the Benefit
We read with great interest the article by Studer et al.1 This article offers several new insights into the use of androgen deprivation therapy (ADT) early in the prostate cancer disease process. This trial demonstrated statistically significant improvements in subjective and objective disease progression and in the overall survival (OS) of men with nonmetastatic prostate cancer who were not candidates for local therapy and were treated with immediate ADT. These differences emerged despite the fact that treatment was started earlier than mandated by protocol in 22% of all patients (or 50% of patients who initiated delayed ADT), due to asymptomatic disease progression, making it more likely that any real differences between the arms would be underestimated.
Surprisingly, the improvement in OS in the immediate ADT arm was due primarily to a decrease in cardiovascular deaths and second primary tumors, rather than to an increase in prostate cancer survival. Although assignment of cause of death is inherently subjective, it does not seem likely that men on the deferred treatment arm, who developed symptomatic disease progression earlier, would have been less likely to have their deaths attributed to prostate cancer. Knowing the number of patients who died with metastatic disease in each arm might help address the possibility of misclassification bias. It is also possible that the increase in cardiovascular mortality observed in the delayed ADT arm was due to increased thrombotic events secondary to more advanced cancer, or to an increase in the number of deaths from tumor emboli, both of which have been associated with advanced prostate cancer.2-5 However, there does not appear to be a plausible explanation for the reduction in second primary tumors. Thus, the finding of no improvement in disease-specific survival despite an improvement in OS should be viewed cautiously.
Importantly, this trial does provide convincing data that the early use of ADT does not lead to earlier symptomatic or radiographic progressive disease with androgen independent prostate cancer (AIPC). While it is not surprising that there was an improvement in time to first symptomatic progression or first objective progression with early ADT, the finding that there was no difference in time to progression after AIPC allays concerns that the earlier use of ADT would be likely to result in the earlier development of hormone refractory disease.
Thus we feel that this is the strongest evidence to date for the use of early ADT in patients with nonmetastatic prostate cancer who are not candidates for local therapy. There is meaningfully improved overall survival, improved time to objective and symptomatic progression, no worse quality of life and no earlier time to progressive AIPC with immediate ADT.
However, we agree with the authors' caution regarding the potential for overtreating such men with hormone ablation. As noted, only 49.7% of men in the delayed treatment group had started ADT by 7 years and were thus spared the known adverse effects of androgen deprivation. A further note of caution is warranted with regard to the temptation to extrapolate these data to the much larger population of men with D0 prostate cancer in whom the potential for harm from long-term ADT may be substantially greater.
The authors indicated no potential conflicts of interest.
This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute Center for Cancer Research.
| 1. | Studer UE, Whelan P, Albrecht W, et al: Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer trial 30891. J Clin Oncol 24: : 1868,2006 -1876, Link, Google Scholar |
| 2. | Sorensen HT, Mellemkjar L, Steffensen FH, et al: The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med 338: : 1169,1998 -1173, Crossref, Medline, Google Scholar |
| 3. | Kohli M, Kaushal V, Mehta P: Role of coagulation and fibrinolytic system in prostate cancer. Semin Thromb Hemost 29: : 301,2003 -308, Crossref, Medline, Google Scholar |
| 4. | Keeping IM, Buchanan R, Dadds JH: Microscopic tumour emboli from carcinoma of the prostate. Br J Dis Chest 76: : 298,1982 -300, Crossref, Medline, Google Scholar |
| 5. | Nakano M, Miwa K, Kanimoto Y, et al: Microscopic pulmonary tumor embolism secondary to adenocarcinoma of the prostate. Hinyokika Kiyo 49: : 169,2003 -172, Medline, Google Scholar |
