Radiation Alone: Is This Sufficient Treatment for Younger Men with Early Stage Prostate Cancer?
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: In a nicely executed matched pair analysis of clinical outcomes after external beam radiation as primary treatment for prostate cancer, younger patients, defined as those 55 years or younger had equivalent outcomes, defined by freedom from biochemical failure, freedom from distant metastases and overall survival at 5 years when compared to older patients. The findings suggest that younger aged patients with localized (organ-confined) disease may be as effectively treated by external beam radiation as older patients, and that the concerns that younger patients have more 'aggressive' disease should not preclude this treatment option.
Source: Konski A, et al. Does age matter in the selection of treatment for men with early stage prostate cancer? Cancer. 2006;106:2598-2602.
Until recently, younger men diagnosed with prostate cancer were frequently not offered external beam radiation as primary therapy on the premise that such would be inadequate for what is likely to be more virulent disease. However, over the past decade, studies have been published which demonstrate that younger patients treated with external beam radiation therapy do not have a higher risk of biochemical failure when compared to older patients with similar stage disease.1,2
The current study was designed to evaluate the effect of external beam radiation alone as a treatment option for younger men with prostate cancer. A retrospective study of 252 patients treated at the Fox Chase Cancer Center between November 1989 and October 2001 were evaluated in the context of age at presentation and overall survival. A matched-pair analysis compared those patients < 55 years (Group 1; n = 84) who were treated with 3-dimension conformal radiation without androgen deprivation to similarly-treated men age > 60 to 70 years (Group 2; n = 84) and men age > 70 years (Group 3; n = 84). The groups were matched with regard to disease stage, Gleason grade, and pre-treatment PSA levels. The majority of men had low-stage, low-grade cancer and received between 70-76 Gy of radiation. Using Kaplan-Meier methodology, there was no statistically significant difference found in the biochemical disease-free survival, freedom from distant metastasis or overall survival among the 3 groups at 5 years.
Commentary
The goal of the current study was to evaluate outcome in a cohort of men age < 55 years with localized prostate cancer who were treated with external beam radiation therapy with similar treatment in older patients. The commonly held notion that younger patients have more aggressive disease would predict that those younger patients would not have equivalent treatment outcomes, but this turned out not to be the case. For all examined parameters the responses among the three age groups were nearly identical.
A study such as this is only as good as the effort to assure comparability among the groups. Indeed, a credible job was done in this regard, matching individuals in each group by stage, grade and PSA. Yet, one can not help but have the concern that prostate cancer patients less than 55 years of age referred for primary external beam radiation as opposed to alternative radiotherapy approaches or radical prostatectomy are somewhat atypical, either because of existing co-morbidities or other complicating factors and that younger patients who were otherwise healthy might be the same individuals for whom aggressive tumor growth would be predicted. Thus, the report would have been strengthened had the matching process included the presence or absence of certain key co-morbidities or functional impairments.
That stated, the results are consistent with other reports comparing outcomes in younger vs. older prostate cancer patients.1-4 The same group from Fox Chase had earlier reported that men < 65 years did not have a worse outcome compared with those > 65 years.1 Furthermore, Zelefsky et al2 found comparable rates of biochemical failure between younger (< 60 years) and older (> 60 years) prostate cancer patients after external beam radiation. Similar lack of age differences in outcome have been reported for those treated with surgical approaches.3,4 The added value from the current report is the careful effort at matching younger and older patients with regard to Gleason grade, stage and PSA, the mismatch of which could have confounded earlier analyses.
Are we to dispense with this notion that younger patients with prostate cancer have more aggressive disease? Probably not, for several reasons. In an extensive analysis of the NCI SEER (Surveillance, Epidemiology and End Results) data, Merrill and Bird5 found that the 5-year relative survival rate increased, leveled off and then decreased over the age span. Conditional death hazards demonstrating statistically significantly higher hazard ratios in men age 40-44 years and age 45-49 years included locoregional stage, distant stage and poorly differentiated or undifferentiated tumors. Their analysis (which included nearly 290,000 cases) allowed the conclusion that younger age was a negative prognostic factor for prostate cancer survival, but this was most apparent for the youngest of patients (< 45 years), and not apparent after a certain age threshold is reached. This is a situation reminiscent of breast cancer in which indolent disease is more apparent in older patients and aggressive disease more frequently observed in the youngest.6
References
1. Freedman GM, et al. Young patients with prostate cancer have an outcome justifying their treatment with external beam radiation. Int J Radiat Oncol Biol Phys. 1996;35:243-250.
2. Zelefsky MJ, et al. Improved biochemical disease-free survival of men younger than 60 years with prostate cancer treated with high dose conformal external beam radiotherapy. J Urol. 2003;170:1828-1832.
3. Kerr LA, Zincke H. Radical retropubic prostatectomy for prostate cancer in the elderly and the young: complications and prognosis. Eur Urol. 1994;25:305-311.
4. Khan MA, et al. Long-term cancer control of radical prostatectomy in men younger than 50 years of age: update 2003. Urology. 2003;62:86-91.
5. Merrill RM, Bird JS. Effect of young age on prostate cancer survival: a population-based assessment (United States). Cancer Causes Control. 2002;13:435-443.
6. Vicini FA, Recht A. Age at diagnosis and outcome for women with ductal carcinoma-in-situ of the breast: a critical review of the literature. J Clin Oncol. 2002;20:2736-2744.
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