Does neoadjuvant hormone therapy improve outcome in prostate cancer patients receiving radiotherapy after radical prostatectomy?

PURPOSE: To assess outcome and predictive factors in men with prostate cancer who receive post radical prostatectomy (RP) radiotherapy (RT) either in the adjuvant or salvage setting, with or without neoadjuvant androgen deprivation therapy (NADT). METHODS: A retrospective analysis was performed on 175 patients with clinically localized prostate cancer treated with RP who subsequently received RT (dose range 50 Gy-68 Gy). Twenty-two patients received adjuvant RT (ART), 57 received NADT + ART, 15 received salvage RT (SRT), and 81 received NADT + SRT. Outcome was assessed by biochemical disease free survival (BDFS), prostate cancer specific survival and overall survival (OS). RESULTS: Although BDFS favored patients who received NADT with 5 year rates of 67%, 80%, 27% and 62% for the ART, NADT + ART, SRT, and NADT + SRT groups respectively; this was not a significant predictor on multivariable analysis. Significant independent predictive factors of improved BDFS were pre-RT PSA < or = 0.2 ng/ml, low Gleason score and positive surgical margins. Age and Gleason score were independent predictors of OS. CONCLUSIONS: Pre-RT PSA is an important predictor of outcome. NADT appears to benefit patients who presented with a pre-RT PSA > 0.2 ng/ml, particularly for patients receiving SRT. NADT can be considered for patients receiving RT after RP who present with a high pre-RT PSA but may not be necessary for patients without. Results of ongoing randomized studies such as RADICALS will also help clarify the role of hormone therapy in conjunction with RT.

Standard treatments induce antigen-specific immune responses in prostate cancer.

PURPOSE: Prostate tumors express antigens that are recognized by the immune system in a significant proportion of patients; however, little is known about the effect of standard treatments on tumor-specific immunity. Radiation therapy induces expression of inflammatory and immune-stimulatory molecules, and neoadjuvant hormone therapy causes prominent T-cell infiltration of prostate tumors. We therefore hypothesized that radiation therapy and hormone therapy may initiate tumor-specific immune responses. EXPERIMENTAL DESIGN: Pretreatment and posttreatment serum samples from 73 men with nonmetastatic prostate cancer and 50 cancer-free controls were evaluated by Western blotting and SEREX (serological identification of antigens by recombinant cDNA expression cloning) antigen arrays to examine whether autoantibody responses to tumor proteins arose during the course of standard treatment. RESULTS: Western blotting revealed the development of treatment-associated autoantibody responses in patients undergoing neoadjuvant hormone therapy (7 of 24, 29.2%), external beam radiation therapy (4 of 29, 13.8%), and brachytherapy (5 of 20, 25%), compared with 0 of 14 patients undergoing radical prostatectomy and 2 of 36 (5.6%) controls. Responses were seen within 4 to 9 months of initiation of treatment and were equally prevalent across different disease risk groups. Similarly, in the murine Shionogi tumor model, hormone therapy induced tumor-associated autoantibody responses in 5 of 10 animals. In four patients, SEREX immunoscreening of a prostate cancer cDNA expression library identified several antigens recognized by treatment-associated autoantibodies, including PARP1, ZNF707 + PTMA, CEP78, SDCCAG1, and ODF2. CONCLUSION: We show for the first time that standard treatments induce antigen-specific immune responses in prostate cancer patients. Thus, immunologic mechanisms may contribute to clinical outcomes after hormone and radiation therapy, an effect that could potentially be exploited as a practical, personalized form of immunotherapy.

Neoadjuvant hormone therapy and external-beam radiation for localized high-risk prostate cancer: the importance of PSA nadir before radiation.

PURPOSE: To examine the impact of various patient, disease, and treatment characteristics on outcome in patients treated with neoadjuvant hormone therapy (NAHT) and external-beam radiation therapy (EBRT) for clinically localized, high-risk prostate adenocarcinoma (initial prostate-specific antigen [PSA] level >20, Gleason score 8-10 or Stage > or = T3). METHODS AND MATERIALS: A retrospective chart review was conducted on 407 patients treated between 1991 and 2001 with NAHT and EBRT for high-risk prostate cancer. The effect of tumor (PSA level, Gleason score, and T stage) and treatment (NAHT duration, total-hormone duration, preradiation PSA) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival, and overall survival were examined. RESULTS: Median follow-up time was 78 months (range: 5-140 months). Actuarial bDFS at 5 years was 52% (95% confidence interval [CI], 46% to 57%) for the entire group. On multivariate analysis, initial PSA level (p = 0.004), Gleason score (p = 0.005), and preradiation PSA level (p < 0.001) were predictive of bDFS, whereas age, T stage, duration of NAHT, and duration of total hormone therapy were not predictive of outcomes. Gleason score and preradiation PSA level were also predictive of prostate cancer-specific survival rates. CONCLUSION: Improved bDFS in patients with high-risk prostate cancer was associated with lower initial PSA level, lower Gleason score, and lower preradiation PSA level. The duration of NAHT did not have an impact on outcomes, but the preradiation PSA was an important predictor of bDFS in high-risk patients.

Modulation of afferent inflow during the control of balancing tasks using the lower limbs.

This study investigated the control of sensory inputs during the performance of an inverted-pendulum balancing task. Experiments were conducted to examine modulation of proprioceptive inputs during balance tasks of varying difficulty. It was hypothesized that proprioceptive inputs to both spinal and cortical levels would be facilitated during a challenged balance task. In contrast, during challenged balance control, results revealed task-specific facilitation of sensory inputs to the cortex and inhibition of the spinal reflex pathway. Observations of increased transmission of proprioceptive inputs to the cortex and decreased transmission at the spinal level suggest that the cortex plays an important role in challenged balance, whereas the role for the spinal stretch reflex appears to be less important.