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The majority of patients with prostate cancer who later develop lethal metastatic disease have high-risk localized disease at presentation, emphasizing the importance of effective treatment strategies at this stage. Multimodal treatment approaches that combine systemic and local therapies offer a promising strategy for improving the clinical outcomes of patients with high-risk localized prostate cancer. Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumours and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes. However, although the combination of androgen deprivation therapy and radiotherapy is a standard of care in high-risk localized or locally advanced prostate cancer, the benefit of chemotherapy or chemohormonal therapy has yet to be demonstrated outside of the metastatic setting. Moreover, the benefit of neoadjuvant and/or adjuvant systemic therapies in combination with radical prostatectomy has not been proved. The development of next-generation hormonal agents, which have been approved for the treatment of castration-resistant prostate cancer, offers further therapeutic possibilities that are being assessed in early-phase clinical trials.

Background To analyze data on patients with localized prostate cancer who were treated with complete high-intensity focused ultrasound (HIFU) prospectively captured within a voluntary HIFU user database (@-Registry). Methods The @-Registry includes data from consecutive patients treated with Ablatherm (EDAP-TMS) HIFU at nine European Centres during the period 1994 and 2009. For this analysis, the data repository was reviewed for information on patients with localized prostate cancer (T1 -- T2) treated with complete (whole-gland) HIFU on the basis of an anterior-posterior prostate height of ≤24 mm and a treated volume >120% of the prostate volume. Patients were regularly followed with PSA measurement and biopsy. Biochemical failure was defined for this study as PSA nadir +2 ngml(-1) (Phoenix definition). Disease-free survival was based on a biopsy, retreatment and biochemical data. Patients were risk group-stratified using the D'Amico classification system. Results The median follow-up was 2.8 years for the 356 patients included in the analysis. The majority could be classified as either low (44.9%) or intermediate risk (39.6%); 14.6% patients were classified as high risk. The median (mean, s.d.) PSA nadir was 0.11 ng ml(-1) (0.78 and 3.6), achieved at a mean (s.d.) of 14.4 (11.6) weeks after HIFU. Follow-up biopsies on 226/356 (63.5%) patients revealed an overall negative biopsy rate of 80.5% (182/226); there was no statistically significant difference in positive biopsy rate by risk group-stratification. Actuarial freedom from biochemical recurrence at 5 and 7 years according to the Phoenix definition was 85% and 79%, respectively. Disease-free progression rates at 5 and 7 years were 64% and 54%, respectively. Conclusions Whole-gland prostate HIFU as primary monotherapy for localized prostate cancer achieves a recurrence-free survival in short-term analysis as assessed by prostate biopsy and serum PSA endpoints in a majority of patients.

The epidermal growth factor receptor (EGFR) pathway is a very well-known pathway implicated in proliferation, growth and metastatic development of various tumor types. Consequently, EGFR pathway inhibitors have provided clinical benefits in many tumor types. EGFR expression is reported in up to 95% of renal cell carcinoma (RCC) and is considered high (3+) in up to 60%. In preclinical models, the EGFR pathway appears implicated in tumor development. Its mode of action includes the common EGFR signal transduction cascades, but it also interacts with the angiogenic pathway, especially the vascular endothelial growth factor receptor (VEGFR) pathway. Monotherapy with EGFR pathway inhibitors does not appear to modify the history of metastatic RCC (MRCC) and does not justify further experiments in this setting. The issues now requiring attention are the degree to which the EGFR pathway is involved in RCC tumors expressing high EGFR levels—a phase III study suggests that it influences outcome in these patients—and the clinical benefit of associating antiangiogenic therapy and EGFR pathway inhibitors in the light of successive phases II trials. In conclusion, the EGFR pathway is probably not a major pathway in RCC development compared to the antiangiogenic pathways, but could play a role in association with antiangiogenics or in the event of progression after antiangiogenic therapy. Additional preclinical data is needed to support these hypotheses.