Reply to Endre Zoltan Neulander and Zev Wejsman's Letter to the Editor re: Martin Spahn, Steven Joniau, Paolo Gontero, et al. Outcome Predictors of Radical Prostatectomy in Patients With Prostate-Specific Antigen Greater Than 20 ng/ml: A European Multi-Institutional Study of 712 Patients. Eur Urol 2010;58:1-7
We thank Neulander and Wejsman for their letter to the editor of European Urology, underlining the usefulness of radical prostatectomy (RP) in the treatment of men with initial prostate-specific antigen (PSA) >20 ng/ml . We appreciate the conclusions drawn from a single-centre study of 85 patients with PSA >15 ng/ml who were treated with RP : Patients with high PSA levels but a Gleason score ≤7 are at minimal risk for prostate cancer (PCa)–specific mortality and thus are excellent candidates for surgery monotherapy. Patients with high-grade tumours or all three high-risk factors are at significant risk for tumour progression . We agree with Neulander and Wejsman that a multimodality approach may be helpful in these cases . Hormone treatment (HT) and radiation therapy are possible adjuvant or salvage options.
The role of adjuvant HT is still controversial, and it is unclear whether HT should be initiated immediately in every high risk case after RP, even for pathologic node-positive patients. A recent Cochrane review and meta-analysis did not find an overall 10-yr survival benefit for neoadjuvant or adjuvant HT and RP . However, we note that high-risk PCa patients were underrepresented in the included studies; for example, the Early Prostate Cancer Trial was not included. McLeod et al observed a significant improvement in objective progression-free survival (PFS) in the combined treatment group after a median follow-up of 7.2 years. This improvement was only significant in the locally advanced disease group (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.61–0.91) . We confirmed these findings in a matched analysis of lymph node–negative high-risk PCa patients with unfavourable histopathology (≥T3 with or without positive surgical margin) who underwent either immediate adjuvant or deferred HT in case of PSA recurrence. PFS was significantly influenced (97.7% vs 83.2%; p = 0.0024), but only a nonsignificant trend was observed for cancer-specific survival (none vs four cancer-related deaths; p = 0.062). This issue becomes critical when considering that 43% of patients in the deferred treatment arm never required HT during follow-up .
Adjuvant radiation therapy is recommended for patients with pT3pN0 and positive surgical margins and/or seminal vesicle invasion, resulting in an overall survival improvement of 1.9 yr . However, the number needed to treat is 9.1 to save one life after 12.6 yr .
We initiated our multicentre study to identify patients at high risk for progression, searching for clinical and molecular risk factors and translating them to the clinic. To meet this goal, we now focus on nomogram development  and on the expression of micro RNAs (miRNAs), molecules that regulate gene expression . We recently revealed a specific pattern of dysregulated miRNA in high-risk PCa that is associated with tumour progression, poor prognosis, and metastasis . The prognostic relevance of both clinical and molecular markers, used in isolation or combination, may enable the prediction of the individual risk for PCa progression and cancer-related death. Therefore, we hope to develop optimised and individualised therapeutic strategies for PCa patients.