Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group

Authors


Sir,

The comparative analyses of Grimm et al. [1] defined reasonable inclusion criteria for studies to be included in their analysis but the results for high-risk patients appear to be biased, because consecutive reports of certain institutions were included multiple times, some surgical and external-beam radiotherapy (EBRT) series were not included and other errors were made as outlined below.

Six series referred to as ‘EBRT + seeds + androgen-deprivation therapy (ADT)’ in Figure 3 of the article, merely reflect the experience of only two centres. Reference #58 seems to contain both prior reported #18 and #59. Reference #20 comes from the same institution, describes however treatment without ADT and only 127 patients were high-risk. For the remaining references #23 and #60 the included sample size might be reconsidered.

Series referred to as ‘EBRT + seeds’ in fact did not use EBRT at all (Reference #26 and #62), or only in a subset of patients (#22). One study actually used high-dose-rate (HDR) brachytherapy in conjunction with EBRT (#44) and at least in a subset of patients ADT was used (References #11, #12, #41, #42, #44, #58, #61, #62). Inclusion of multiple reports on the same patient cohorts necessitates recalculation also in this treatment group.

For the treatment group ‘HDR’, Reference #65 should refer to Deger et al. European Urology 2005, Reference #45 might be replaced by Reference #44 (which was referred to as EBRT + seeds) and in Reference #66 the 3.3-year (not 8-year) biochemical control was 88.5% (compare Figure 3).

For series referred to as ‘EBRT’, Reference #56 used RT doses <72 Gy and should not be eligible for the present analysis. The sample size of Reference #35 should be reconsidered, as some of the included patients underwent RT with <72 Gy. Reference #33 might be excluded as it remains unclear how many of the conventional high-risk patients (n = 272) received a total dose of ≥72 Gy. The stated sample size based on the MD Anderson
dose escalation trial should be reconsidered
(n = 53 not n = 1256, Figure 3, Reference #67). Importantly, results from other dose-escalation trials, meeting the inclusion criteria for the present analysis, were not included: The Medical Research Council RT01 trial reported a 5-year biochemical progression-free survival rate of 57% for 184 patients treated within the dose-escalated arm after neoadjuvant ADT [2] and the Dutch trial described a 6-year freedom-from-failure rate of 49%, based on 179 patients from the experimental arm, most of which underwent either short- or long-term ADT [3].

Importantly, series referred to as ‘Surgery’ should also be reconsidered with respect to multiple inclusion of the same patient cohorts (References #50 and #54 as well as #5 and #57). Reference #57 described a 15-year biochemical recurrence-free survival of 38%, which seems not accounted for in Figure 3 of the present article. It should be noted that inclusion of surgical series using prostatectomy specimen Gleason score for risk stratification, might introduce a bias when compared with RT studies (Reference #50, #52, #53, #54). For unclear reasons, surgical reports, meeting the inclusion criteria and reporting favourably comparing results were not included. Freedland et al.
[4] described a 15-year biochemical progression-free survival rate of 49% for 56 patients with clinical stage cT3a disease and Spahn et al. [5] described a 10-year biochemical progression-free survival rate of 52% for 712 patients with a PSA level of >20 ng/mL treated within a multi-institutional study.

We also wonder why the numbers of high-risk studies mentioned in Table 3 does not match the study count listed in Figure 3 for some of the treatment groups.

The authors should be acknowledged for attempting a comprehensive meta-analysis. However, consideration of the concerns raised above may lead to different results and conclusions regarding treatment of patients with high-risk prostate cancer. We fear that the article in its present form fails to provide ‘evidence-based prostate cancer treatment comparisons’, as stated by the authors.

Acknowledgements

P.G. was supported by the Swiss Foundation for Medical-Biological Scholarships (SSMBS) and the Eugen & Elisabeth Schellenberg Foundation.

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