Psychological functioning associated with prostate cancer: cross-sectional comparison of patients treated with radiotherapy, brachytherapy, or surgery.

This study compared the prevalence of psychological difficulties (i.e., anxiety and depression), psychophysiological problems (i.e., insomnia and fatigue), and sexual difficulties across three modalities of treatment for prostate cancer (radiotherapy, brachytherapy, and radical prostatectomy). A total of 861 men completed a battery of questionnaires assessing anxiety, depression, fatigue, insomnia, and quality of life. Patients who initially received radiotherapy had higher levels of depression, anxiety, and fatigue and a lower quality of life, and were more likely to report clinical levels of depression and fatigue. Patients who initially received surgery were more likely to report clinical levels of sexual difficulties but less likely to report clinical levels of depression and fatigue, while patients who received brachytherapy were less likely to report sexual difficulties. Although cross-sectional, these findings raise the possibility of a differential influence of treatments for prostate cancer on some aspects of psychological functioning.

Performing daily prostate targeting with a standard V-EPID and an automated radio-opaque marker detection algorithm.

Online prostate positioning using gold markers and a standard video-based electronic portal imaging device is reported. The average systematic (random) errors have been reduced from 2.1 mm (2.7 mm) to 0.5 mm (1.5 mm) in AP direction, 1.1 mm (1.7 mm) to 0.7 mm (1.2 mm) SI and 1.2 mm (1.7 mm) to 0.6 mm (1.3 mm) LR.

Measurements of intrafraction motion and interfraction and intrafraction rotation of prostate by three-dimensional analysis of daily portal imaging with radiopaque markers.

PURPOSE: To measure the interfraction and intrafraction motion of the prostate during the course of external beam radiotherapy using a video electronic portal imaging device and three-dimensional analysis. METHODS AND MATERIALS: Eighteen patients underwent implantation with two or three gold markers in the prostate before five-angle/11-field conformal radiotherapy. Using CT data as the positional reference, multiple daily sets of portal images, and a three-dimensional reconstruction algorithm, intrafraction translations, as well as interfraction and intrafraction rotations, were analyzed along the three principal axes (left-right [LR], superoinferior [SI], and AP). The overall mean values and standard deviations (SDs), along with random and systematic SDs, were computed for these translations and rotations. RESULTS: For 282 intrafraction translational displacements, the random SD was 0.8 mm (systematic SD, 0.2) in the LR, 1.0 mm (systematic SD, 0.4) in the SI, and 1.4 mm (systematic SD, 0.7) in the AP axes. The analysis of 348 interfraction rotations revealed random SDs of 6.1 degrees (systematic SD, 5.6 degrees ) around the LR axis, 2.8 degrees (systematic SD, 2.4 degrees ) around the SI axis, and 2.0 degrees (systematic SD, 2.2 degrees ) around the AP axis. The intrafraction rotational motion observed during 44 fractions had a random SD of 1.8 degrees (systematic SD, 1.0 degrees ) around the LR, 1.1 degrees (systematic SD, 0.8 degrees ) around the SI, and 0.6 degrees (systematic SD, 0.3 degrees ) around the AP axis. CONCLUSION: The interfraction rotations observed were more important than those reported in previous studies. Intrafraction motion was generally smaller in magnitude than interfraction motion. However, the intrafraction rotations and translations of the prostate should be taken into account when designing planning target volume margins because their magnitudes are not negligible.

Activity and safety of the antiestrogen EM-800, the orally active precursor of acolbifene, in tamoxifen-resistant breast cancer.

PURPOSE: To determine the efficacy and safety of EM-800 (SCH-57050), the precursor of acolbifene, a new, highly potent, orally active, pure antiestrogen in the mammary gland and endometrium, for the treatment of tamoxifen-resistant breast cancer. PATIENTS AND METHODS: Forty-three post menopausal/ovariectomized women with breast cancer who had received tamoxifen, either for metastatic disease or as adjuvant to surgery for > or = 1 year, and had relapsed were treated in a prospective, multicenter, phase II study with EM-800 (20 mg/d [n = 21] or 40 mg/d [n = 22] orally). Results Thirty-seven patients had estrogen receptor (ER)-positive tumors (>10 fmol/mg; mean, 146 fmol/mg cytosolic protein), three patients had ER-negative/progesterone receptor-positive tumors, and three patients had undetermined ER status. The objective response rate to EM-800 was 12%, with one complete response and four partial responses. Ten patients (23%) had stable disease for > or = 3 months, and 7 patients (16%) had stable disease for > or = 6 months. With a median follow-up of 29 months, median duration of response was 8 months (range, 7 to 71+ months). Treatment with EM-800 was well tolerated. No significant adverse events related to the study drug were observed clinically or biochemically. CONCLUSION: EM-800 produced responses in a significant proportion of patients with tamoxifen-resistant breast cancer, thus showing that this highly potent, selective estrogen receptor modulator, which lacks estrogenic activity in the mammary gland and endometrium, has incomplete cross-resistance with tamoxifen, thus suggesting additional benefits in the treatment of breast cancer.

The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer.

PURPOSE: We evaluated the benefits and sequencing of androgen suppression (AS) administered with external beam radiation therapy (EBRT) in T2-T3 prostate cancers. MATERIALS AND METHODS: Between 1990 and 1999, 481 patients were entered in 2 successive, prospective, randomized studies, including 161 in the study 1 and 325 in study 2. Eligible patients had clinical stages T2-T3 prostate cancer. In the first study (L-101) subjects were randomly allocated among EBRT alone (group 1), EBRT preceded by 3 months of AS (group 2), and neoadjuvant, concomitant and adjuvant AS for a total of 10 months (group 3). In the second study (L-200) we analyzed neoadjuvant and concomitant AS (total 5 months) vs neoadjuvant, concomitant and short course adjuvant (total 10 months) AS with EBRT. In each study we used a total AS (a luteinizing hormone-releasing hormone agonist plus an antiandrogen) and a standard dose of radiation therapy at that time. Patient characteristics were well balanced in regard to age, stage, prostate specific antigen and Gleason score. No biochemical evidence of disease (BNED) was defined as an end point according to the Vancouver rule. RESULTS: In the study 1 at a median followup of 5 years 7-year biochemical-free survival rates were 42%, 66% and 69% in groups 1 to 3, respectively. BNED was significantly different between groups 1 and 2 (p = 0.009) and between groups 1 and 3 (p = 0.003) but not between groups 2 and 3 (p = 0.6). Multivariate analysis using a Cox proportional hazards model showed an HR of 6.1 for Gleason score (p = 0.001), 1.4 for PSA (p = 0.002), 0.5 for group 1 vs group 2 (p = 0.01) and 0.35 for group 1 vs group 3 (p = 0.008). In study 2 BNED at 4 years was 65%. There was no significant difference between arms 1 and 2 (p = 0.55). CONCLUSIONS: The analysis of study 1 shows a benefit of using a short course of neoadjuvant AS with EBRT vs EBRT alone for localized T2-T3 prostate cancers. Moreover, in each study adding a short course of adjuvant AS after neoadjuvant 1 provided no more advantage in these patients.

Expression of p21 cell cycle protein is an independent predictor of response to salvage radiotherapy after radical prostatectomy.

BACKGROUND: To assess whether the expression of p21, p27, and p53 could predict biochemical failure in prostate cancer patients treated with neoadjuvant androgen deprivation prior to salvage radiotherapy for a rising post-radical prostatectomy (RP) prostate-specific antigen (PSA). METHODS: The expression of p21, p27, and p53 was determined by immunohistochemistry in a cohort of 74 formalin-fixed paraffin-embedded prostate cancer samples obtained from RP. Expression of these markers was then correlated with clinicopathological parameters and biochemical failure-free survival after salvage radiotherapy. RESULTS: Expression of p21, p27, and p53 was observed in 20%, 69%, and 74% of prostate cancer specimens, respectively. Overexpression of p21 correlated with a higher Gleason score (>7) (P = 0.024). Of the three markers, only p21 expression was correlated with PSA failure after radiotherapy (P = 0.034). In multivariate analysis, both positive p21 (P = 0.004) and pre-radiation serum PSA > 1 ng/ml (P < 0.0001) were independent predictors of biochemical failure after salvage radiotherapy. Patients with p21- tumors and a serum PSA level < or = 1 ng/ml before salvage radiotherapy had a biochemical failure-free survival at 5 years of 83%, compared to 16% at 5 years for those patients with either p21+ tumor or a PSA > 1 ng/ml. Patients with both p21+ and a PSA level > 1 ng/ml had a much lower biochemical failure-free survival rate of 25% at only 18 months (P < 0.0001). CONCLUSIONS: The expression of p21 in prostatectomy specimens could help predict the likelihood of response to salvage radiotherapy, particularly in patients treated before PSA reaches 1 ng/ml.

Neoadjuvant hormone therapy before salvage radiotherapy for an increasing post-radical prostatectomy serum prostate specific antigen level.

PURPOSE: We retrospectively evaluated the benefit of neoadjuvant androgen deprivation therapy administered before salvage external beam radiation treatment in patients with biochemical failure following retropubic radical prostatectomy (RRP). MATERIALS AND METHODS: A total of 81 patients were treated with neoadjuvant androgen deprivation therapy before salvage external beam radiation treatment because of an increased prostate specific antigen (PSA) level following RRP. Preoperative, pathological, postoperative, and pre-salvage treatment parameters and radiation therapy dosage were examined for influence on outcome. Biochemical failures after RRP or salvage external beam radiation treatment were defined as a PSA greater than 0.3 ng/ml on 2 consecutive measurements. Median radiation dose delivered was 60 Gy. Neoadjuvant androgen deprivation therapy consisted of a 3 month injection of a luteinizing hormone releasing hormone analogue. Median followup was 38 months (range 12 to 102) after completion of external beam radiation treatment and 91 months (range 20 to 163) after radical prostatectomy. RESULTS: The actuarial free biochemical failure rates at 3 and 5 years were 75% and 50%, respectively. Two patients (2%) died of prostate cancer. Significant predictors of response to salvage external beam radiation treatment on a univariate analysis were a pre-radiation serum PSA less than 1 ng/ml and a pathological Gleason score less than 7. However, only pre-radiation PSA remained statistically significant on a multivariable analysis. CONCLUSIONS: External beam radiation with neoadjuvant androgen deprivation therapy is a viable option for patients with an increasing post-prostatectomy serum PSA. The most powerful predictor of biochemical failure was pre-radiation serum PSA.