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Background Prednisolone is widely used as secondary hormonal treatment for castration-resistant prostate cancer (CRPC). We hypothesised that dexamethasone, another corticosteroid, is more active. Objective To compare the activity of prednisolone and dexamethasone in CRPC. Design, setting, and participants This single-centre, randomised, phase 2 trial was performed in 82 men with chemotherapy-naïve CRPC enrolled from 2006 to 2010. Intervention Prednisolone 5 mg twice daily versus dexamethasone 0.5 mg once daily versus intermittent dexamethasone 8 mg twice daily on days 1–3 every 3 wk. Outcome measurements and statistical analysis The main end point was prostate-specific antigen (PSA) response rate. Secondary end points included time to PSA progression, radiologic response rate using Response Evaluation Criteria In Solid Tumors (RECIST), and safety. Results and limitations The intermittent dexamethasone arm was dropped after no response was seen in seven patients. By intention to treat, confirmed PSA response was seen in 41% versus 22% for daily dexamethasone versus prednisolone, respectively ( p = 0.08). In evaluable patients, the PSA response rates were 47% versus 24% for dexamethasone and prednisolone, respectively ( p = 0.05). Median time to PSA progression was 9.7 mo on dexamethasone versus 5.1 mo on prednisolone (hazard ratio: 1.6; 95% confidence interval, 0.9–2.8). In 43 patients with measurable disease, the response rate by RECIST was 15% and 6% for dexamethasone and prednisolone, respectively ( p = 0.6). Of 23 patients who crossed over at PSA progression on prednisolone, 7 of the 19 evaluable (37%) had a confirmed PSA response to dexamethasone. Clinically significant toxicities were rare. Conclusions Dexamethasone may be more active than prednisolone in CRPC. In the absence of more definitive trials, dexamethasone should be used in preference to prednisolone. Patient summary We compared two different steroids used for treating men with advanced prostate cancer. Our results suggest that dexamethasone may be more effective than prednisolone and that both are well tolerated. Clinical trial registry EUDRAC 2005-006018-16 [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the prostate-specific antigen (PSA) response rate and duration of PSA response to dexamethasone in patients with castration-refractory prostate cancer (CRPC), as corticosteroids are frequently used as second-line hormonal treatment of CRPC and there is little published evidence concerning the efficacy of low-dose dexamethasone in this setting. PATIENTS AND METHODS In all, 102 patients with progressive CRPC received oral dexamethasone (0.5 mg daily) between January 2003 and October 2006. The median pretreatment PSA level was 83 ng/mL. The main endpoint was the PSA response rate according to the PSA Working Group criteria. RESULTS In all, 50 patients (49%) had a confirmed PSA response. The median (range) time to PSA progression for the entire cohort was 7.4 (1–28) months. In responders, the median duration of the PSA response was 11.6 (1–24) months. CONCLUSION Low-dose dexamethasone has significant activity in CRPC. Subject to validation with more clinically meaningful endpoints, dexamethasone could become the corticosteroid of choice in the management of CRPC, and its potential for use in combination with novel agents should be explored. [ABSTRACT FROM AUTHOR]

OBJECTIVE To report the results of a prospective study of active surveillance of untreated prostate cancer, with a focus on baseline predictors of prostate-specific antigen (PSA) velocity, as PSA velocity before treatment is an important predictor of prostate cancer mortality, and patients on active surveillance are monitored for several years to estimate the PSA velocity and thus select patients for radical treatment. PATIENTS AND METHODS A prospective study of active surveillance for localized prostate cancer opened at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a, N0/Nx, M0/Mx adenocarcinoma of the prostate with a serum PSA level of <15 ng/mL, a Gleason score of ≤7 with primary grade ≤3, and less than half the biopsy cores positive. The PSA velocity before treatment was analysed in relation to baseline clinical characteristics. RESULTS In all, 237 patients on surveillance were followed for a median of 24 months (median age 67 years; median initial PSA level 6.5 ng/mL; median pretreatment PSA velocity 0.44 ng/mL per year). On multivariate analysis, PSA density (i.e. serum PSA level/prostate volume) was the only significant determinant of PSA velocity ( P < 0.001). Patients with a PSA density above or below the median (0.185 ng/mL/mL) had a median (interquartile range) PSA velocity of 0.92 (0.34–1.77) ng/mL per year and 0.35 (− 0.06, 0.80) ng/mL per year, respectively. CONCLUSIONS PSA density, which is readily available at the time of diagnosis, is an independent determinant of PSA velocity in untreated, localized prostate cancer. If this is confirmed, PSA density could be used to inform the often difficult choice between active surveillance and immediate radical treatment. [ABSTRACT FROM AUTHOR]

Purpose: Active surveillance for early prostate cancer is a policy of close monitoring with radical treatment targeted at cases with evidence of disease progression. There is no consensus on the need for or optimum timing of repeat biopsies as part of active surveillance. Materials and Methods: In a prospective cohort study of active surveillance 119 patients with untreated localized prostate cancer (T1/2a), prostate specific antigen less than 15 ng/ml, Gleason score 3 + 4 or less and 50% or less positive cores underwent repeat biopsy after 18 to 24 months. Histological disease progression was defined as primary Gleason grade 4 or greater, greater than 50% positive cores or a Gleason score increase from 6 or less to 7 or greater. The risk of histological disease progression was analyzed with respect to baseline clinical factors. Results: Median patient age was 66 years and median initial prostate specific antigen was 6.6 ng/ml. Histological disease progression was seen in 33 of 119 cases (28%). On multivariate analysis prostate specific antigen density (p = 0.002) and maximum percent involvement of any core (p = 0.04) were significant independent determinants of histological disease progression. Progression was seen in 22 of 40 cases (55%) with prostate specific antigen density 0.2 ng/ml/ml or greater and greater than 15% maximum involvement of any core. Progression was seen in 2 of 33 cases (6%) with prostate specific antigen density less than 0.2 ng/ml/ml and 15% or less maximum involvement of any core. Conclusions: Repeat biopsy should be an integral part of active surveillance for untreated localized prostate cancer. Immediate repeat biopsy should be considered in patients who elect active surveillance but who have prostate specific antigen density greater than 0.2 ng/ml/ml. These findings must be validated in a cohort of patients with extended biopsies at diagnosis and followup. [Copyright &y& Elsevier]

Purpose: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers.Methods and Materials: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity.Results: One hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group.Conclusions: PIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established. [ABSTRACT FROM AUTHOR]