International Journal of Radiation Oncology*Biology*Physics
Clinical investigations: ProstateImproved biochemical relapse-free survival with increased external radiation doses in patients with localized prostate cancer: The combined experience of nine institutions in patients treated in 1994 and 1995
Introduction
A significant controversy still exists in the radiation oncology community with respect to the impact of increasing radiation doses in the treatment of localized prostate cancers 1, 2, 3, 4, 5, 6, 7. Only one relatively mature randomized study, with a total of 301 cases, has been reported, and it showed an improved relapse-free survival rate with 78 Gy vs. 70 Gy in patients with localized prostate cancers (2). Most other retrospective studies addressing the issue of higher radiation doses, although typically including a greater number of cases, have been criticized in part because of differences in the length of follow-up periods between dose groups 8, 9, 10. Because dose escalation has gradually occurred over the past decade, patients treated with higher radiation doses have been treated more recently in comparison with patients treated with lower radiation doses. This implies that patients receiving higher doses would generally have shorter follow-up durations and would potentially include a higher proportion of patients with favorable features because of “stage migration” occurring over time 9, 10. Other criticisms have included improved radiotherapy (RT) techniques and increased use of androgen deprivation in more recent years.
In the absence of randomized studies, carefully conducted large-scale retrospective studies can still be useful to generate hypotheses related to dose escalation. In the current report, the outcomes of patients treated at nine major institutions over a short period (1994–1995) were combined in an attempt to minimize any biases introduced resulting from differences in follow-up durations or any biases introduced secondary to stage migration occurring over extended intervals during which patients would have been diagnosed and treated.
Section snippets
Patient population
Nine participating institutions with long-term follow-up of patients with prostate cancer collaborated on this study. These institutions included the Cleveland Clinic, Fox Chase Cancer Center, Mallinckrodt Institute of Radiology at Washington University, Massachusetts General Hospital, Mayo Clinic Rochester, Memorial Sloan-Kettering Cancer Center, University of Michigan, The University of Texas M. D. Anderson Cancer Center, and William Beaumont Hospital. Institutional Review Board approval was
Pretreatment characteristics
Table 1 summarizes the pretreatment clinical characteristics of all patients in the study sample. Overall, patients receiving ≥72 Gy had higher stage cancers and higher PSA levels. Risk groups, defined on the basis of initial (pretherapy) PSA levels (iPSA) and biopsy Gleason scores (GS), were as follows: low risk—T1b, T1c, T2a, GS ≤6 and iPSA ≤10 ng/mL; intermediate risk—T1b, T1c, T2a, GS ≤6 and iPSA >10 ng/mL but ≤20 ng/mL or T2b, GS ≤6 and iPSA ≤20 ng/mL or GS 7 and iPSA ≤20 ng/mL; and high
Discussion
The present study demonstrated that differences in follow-up duration and the number of follow-up PSA determinations were not factors that accounted for improved outcomes in patients receiving higher-than-standard radiation doses. In this large multi-institutional dataset, the study sample was limited to patients treated within a narrow 2-year period (1994–1995). The median follow-up periods were 5.7 and 5.8 years in the ≥72 Gy and <72 Gy groups. The treatment and follow-up durations were
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