The biochemical efficacy of primary cryoablation combined with prolonged total androgen suppression compared with radiotherapy on high-risk prostate cancer： a 3-year pilot study

To gain beneficial effects in the management of high-risk prostate cancer, an integrated approach that combines local therapy and androgen deprivation therapy （ADT） was used. We compared biochemical responses between primary cryosurgical ablation of the prostate （CSAP） combined with prolonged ADT and radiation combined with ADT, which is the established modality in high-risk disease. A total of 33 high-risk patients received CSAP combined with ADT for 3 months before and up to 24 months after treatment. This patient group was matched with another 33 patients who had undergone three-dimensional conformal radiation therapy （3D-CRT） with the same protocol for ADT. Biochemical recurrence （BCR） was assessed by the American Society for Therapeutic Radiation Oncology （ASTRO） definition, the Phoenix definition and a prostate-specific antigen （PSA） cutoff of 0.5 ng mL^-1. Median follow-up was 61.0 ± 11.9 months for the CSAP ＋ ADT group and 86.0±15.8 months for the 3D-CRT ＋ ADT group. In the CSAP group, major complications including rectourethral fistula and incontinence were not noted. In the CSAP ＋ ADT group, 57.0% had BCR using the ASTRO definition, 21.2% using the Phoenix definition and 54.5% using a PSA cutoff of 0.5 ng mL^-1. In the 3D-CRT ＋ ADT group, 54.5%, 21.2% and 54.5% had BCR using the ASTRO, Phoenix and PSA definition, respectively. In the CSAP ＋ ADT group, the BCR-free survival （BRFS） was 54 ± 10 months using the ASTRO definition, 65 ± 5 months using the Phoenix definition and 51 ± 4 months using a PSA cutoff of 0.5 ng mL-1. In the 3D-CRT ＋ ADT group, the BRFS was 68 ± 12, 93 ± 19 and 70 ± 18 months using the ASTRO, Phoenix and PSA definition, respectively. By the log-rank test, the BRFS values for each group were not statistically different. This intermediate-term result indicated that primary CSAP combined with prolonged ADT offers a parallel biochemical response compared with radiotherapy in high-risk prostate cancer.

Expression of human AR cDNA driven by its own promoter results in mild promotion, but not suppression, of growth in human prostate cancer PC-3 cells

Aim： To examine the physiological role of the androgen receptor （AR） in the PC-3 cell line by transfecting full-length functional AR cDNA driven by its natural human AR promoter. Methods： We generated an AR-expressing PC-3（AR）9 stable clone that expresses AR under the control of the natural human AR promoter and compared its proliferation to that of the PC-3（AR）2 （stable clone that expresses AR under the control of the cytomegalovirus （CMV） promoter, established by Heisler et al.） after androgen treatment. Results： We found that dihydrotestosterone （DHT） from 0.001 nmol/L to 10 nmol/L induces cell cycle arrest or inhibits proliferation of PC-3（AR）2 compared with its vector control, PC-3（plRES）. In contrast, PC-3（AR）9 cell growth slightly increased or did not change when treated with physiological concentrations of 1 nmol/L DHT. Conclusion： These data suggest that intracellular control of AR expression levels through the natural AR promoter might be needed for determining AR function in androgen-independent prostate cancer （AIPC） PC-3 cells. Unlike previous publications that showed DHT mediated suppression of PC-3 growth after transfection of viral promoter-driven AR overexpression, we report here that DHT-mediated PC-3 proliferation is slightly induced or does not change compared with its baseline after reintroducing AR expression driven by its own natural promoter, as shown in PC-3（AR）9 prostate cancer cells.