Endurance, upper extremity strength, and physical components of QOL are affected within 3 months of starting ADT. Up-front exercise interventions to counteract these losses are warranted.

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After 6 years of followup there was no overall benefit with 3 months of NHT. Improved bNED survival was seen in the highest risk PSA group (PSA greater than 20). The possibility that high risk patients may benefit from NHT warrants further investigation.

Neoadjuvant hormonal therapy (NHT; androgen ablation) is used prior to radical prostatectomy (RP) in an attempt to pathologically "downstage" prostatic adenocarcinoma and ultimately to improve disease-free survival. This study describes the pathologic effects of NHT with the antiandrogen cyproterone acetate, 300 mg/day for 12 weeks, on the RP specimens from men with clinically localized (stage T1 or T2) prostatic adenocarcinoma. There were 101 men in the pretreatment group (CPA) and 91 men in a control group who were treated with surgery alone. The prevalence and extent of morphologic effects were recorded for the nonneoplastic prostate, high-grade prostatic intraepithelial neoplasia, and invasive adenocarcinoma. The commonest effects on the nonneoplastic prostate were atrophy and basal cell hyperplasia and prominence. High-grade prostatic intraepithelial neoplasia was more commonly identified in the surgery alone group than the CPA group (p <0.01). In the CPA group, flat and low tufted patterns of high-grade prostatic intraepithelial neoplasia predominated. Following NHT, the adenocarcinoma showed characteristic morphologic alterations, including reduction in cytoplasmic quantity, cytoplasmic vacuolation, nuclear pyknosis, reduced gland diameter, and mucinous breakdown. In many cases there was prominence of collagenous stroma, obscuring malignant glands. Compared with the surgery alone group, the CPA group RP specimens had a significantly lower mean specimen weight (40.3 g vs 46.5 g, p = 0.025) and less tumor extent by several measures. Organ-confined tumor (stage pT2, margin negative) was found in 41.6% of the CPA group compared with 19.8% of the surgery alone group (p = 0.0017). The overall rate of margin positivity was lower in the CPA group (27.7% vs 64.8%, p = 0.001). We consider that the difference in margin positivity is the result of tumor shrinkage with a decreased likelihood of sampling in routine sections. There was no significant difference in the rate of extraprostatic extension between the two groups. There was elevation of the Gleason score in the RP specimens versus baseline biopsy in 60% of the CPA group compared with 33% of the surgery alone group (p = 0.02). The higher rate of elevation in the CPA group largely resulted from an increase in primary or secondary Gleason score 5 tumor, a morphologic artifact introduced by NHT. Because of this, we recommend not giving a Gleason grade to RP specimens following NHT. Monotherapy with CPA has similar pathologic effects on benign and malignant prostate tissue as does dual agent androgen blockade. Prolonged follow-up of these patients is required to determine if NHT with CPA leads to improved disease-free survival.

These results demonstrate that the growth rate of small renal tumors is variable, tumors that are destined to grow and possibly metastasize do so early and most small tumors grow at a low rate or not at all.

3 Background: In men with PSA recurrence after radical radiotherapy (RRT), intermittent androgen suppression (IAS) has been suggested by phase II trials to improve quality of life (QoL) but effects on survival are unknown. In this Intergroup randomized phase III trial, we compared IAS vs continuous androgen deprivation (CAD) to test for non-inferiority of IAS with respect to overall survival (OS). Methods: Eligible men had rising PSA > 3.0 ng/ml >1 year post RRT, either initial or salvage, for localized prostate cancer. Patients could receive up to 1 year of neo/adjuvant androgen deprivation therapy (ADT) completed >1 year prior. Stratification factors were time since RRT (>1-3 vs >3 years), initial PSA (<15 vs >15), prior radical prostatectomy and prior ADT. IAS was delivered for 8 months in each cycle with restart when PSA reached >10 ng/ml off treatment. Primary endpoint was OS; secondary endpoints included time to hormone refractory state (HR), QoL, cholesterol/HDL/LDL, duration of treatment/non-treatment intervals, time to testosterone and potency recovery. The independent DSMC recommended halting the trial after a planned interim analysis demonstrated that a pre-specified stopping boundary for non-inferiority was crossed. Results: 1,386 patients were randomized to IAS (690) or CAD (696) arms. Arms were balanced for important baseline factors. Median follow up was 6.9 years. IAS patients completed a median of 2 x 8 month cycles (range: 1-9). 524 deaths were observed (268 on IAS vs 256 on CAD). Median OS was 8.8 vs 9.1 years on IAS and CAD arms, respectively (HR 1.02, 95%CI 0.86-1.21; p for non-inferiority [HR IAS vs CAD ≥ 1.25] = 0.009). The IAS arm had more disease related (122 vs 97) and fewer unrelated (134 vs 146) deaths. Time to HR was statistically significantly improved on the IAS arm (HR 0.80, 95%CI 0.67-0.98; p = 0.024). IAS patients had reduced hot flashes, but otherwise there was no evidence of differences in AEs, including myocardial events or osteoporotic fractures. Conclusions: In men with PSA recurrence after RRT IAS, given as described herein, is non-inferior to CAD with respect to OS. No significant financial relationships to disclose.

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