Psychometric validation of the Spanish version of the Expanded Prostate Cancer Index Composite-26.

PURPOSE: To assess the validity, reliability, and responsiveness of the Spanish version of the Expanded Prostate cancer Index Composite (EPIC) with 26 items. METHODS: Multicentric longitudinal study of patients diagnosed with localized or locally advanced prostate cancer (any T, any N, M0) treated with active surveillance, surgery, external radiotherapy, or brachytherapy. The EPIC-50 was administered initially to the cohort (n = 324 patients), until it was replaced in November 2019 by the EPIC-26 (n = 543), in both groups before treatment and 12 months after. We assessed confirmatory factor analysis (CFA), reliability with Cronbach's alpha coefficient, criterion validity with the intraclass correlation coefficient (ICC), and responsiveness by testing a priori hypotheses on deterioration effect size (ES). RESULTS: The CFA confirmed the five-domain structure of the EPIC-26 proposed by the original instrument (comparative fit index = 0.95). The agreement between EPIC-50 (gold standard) and EPIC-26 domains was excellent (ICC > 0.90). Cronbach's alpha was > 0.7 in almost all domains, and the floor effect was near zero, although ceiling effect was higher than 50% in urinary incontinence and bowel domains. Hypothesized changes between before and 12 months after treatment were confirmed: ES > 0.8 in both urinary incontinence and sexual domains among patients who underwent surgery; and ES ranging 0.44-0.48 for bowel and sexual domains in patients treated with external radiotherapy. CONCLUSION: The Spanish version of the EPIC-26 has demonstrated adequate metric properties, similar to those of the original version, with acceptable goodness-of-fit indices, good criterion validity, reliability, and responsiveness to detect changes after radical prostatectomy or external radiotherapy.

High-dose radiotherapy and risk-adapted androgen deprivation in localised prostate cancer (DART 01/05): 10-year results of a phase 3 randomised, controlled trial.

BACKGROUND: The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial. METHODS: This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36). FINDINGS: Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed. INTERPRETATION: After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process. FUNDING: Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. PATIENT AND METHODS: Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. RESULTS: At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). CONCLUSION: Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance.

Five-year quality of life in patients with high-risk localized prostate cancer treated with external beam radiotherapy alone versus external beam radiotherapy with high-dose-rate brachytherapy boost: a prospective multicenter study.

PURPOSE: Brachytherapy (BT) and external beam radiation therapy (EBRT) are effective treatments for high-risk prostate cancer (PCa). However, the impact of these treatments on health-related quality of life (HRQL) remains unclear. In this study, we compared EBRT alone with EBRT plus a boost with high-dose rate (HDR)-BT to determine the impact on HRQL in patients with high-risk PCa. MATERIAL AND METHODS: Prospective, multicenter study comparing patients with high-risk PCa treated with EBRT alone or EBRT + HDR-BT from 2004 to 2006. HRQL was assessed at baseline (pre-treatment) and periodically over the 5-year follow-up, using the SF-36 (v.2), EPIC, and FACT-G and FACT-P questionnaires. RESULTS: A total of 129 patients were included in the study, of these, 41 received EBRT alone and 88 EBRT + HDR-BT. All patients received hormonotherapy. Baseline clinical characteristics were similar, except for a slightly higher mean number of comorbidities in the EBRT group. During follow-up, the only significant between-group difference was a greater worsening on EPIC hormonal domain in the EBRT alone group (p = 0.028). There were no significant differences in time and interaction of treatment in SF-36, and FACT-G and FACT-P questionnaires or EPIC urinary incontinence, urinary irritative-obstructive, and bowel and sexual domains over the 5-year follow-up. Oncological outcomes were similar in both groups. CONCLUSIONS: After five years of follow-up, EBRT alone or combined with HDR-BT boost had a similar impact on HRQL in patients with high-risk localized PCa. However, patients in the EBRT alone group experienced greater worsening of hormonal domain according to EPIC questionnaire.

Prognostic value of testosterone castration levels following androgen deprivation and high-dose radiotherapy in localized prostate cancer: Results from a phase III trial.

BACKGROUND/OBJECTIVE: The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT). PATIENTS AND METHODS: The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum <20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery. RESULTS: There were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. CONCLUSIONS: Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Patient-reported outcomes after treatment for clinically localized prostate cancer: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review is to assess the impact of primary treatments with curative intention in patients with localized prostate cancer, measured with Patient-Reported Outcomes (PROs), and to examine differences among modalities within treatments. METHODS: We conducted a systematic literature search for January 2005-March 2017 following PRISMA guidelines, including longitudinal studies measuring disease-specific PROs in localized prostate cancer patients with a follow-up from pre- to post-treatment (≥1 year). Two reviewers independently extracted data and assessed risk of bias. The study is registered in PROSPERO: CRD42015019747. RESULTS: Of 148 identified studies, 60 were included in the meta-analyses. At the 1st year, radical prostatectomy patients showed small urinary irritative-obstructive improvement (0.37SD 95%CI 0.30, 0.45), but large deterioration for sexual function and incontinence with high heterogeneity (I2 = 77% and 93%). Moderate worsening in external radiotherapy patients for sexual function (-0.46SD 95%CI -0.55, -0.36), small urinary incontinence (-0.16SD 95%CI -0.23, -0.09) and bowel impairment (-0.31SD 95%CI -0.39, -0.23). Brachytherapy patients presented small deterioration in urinary incontinence (-0.29SD 95%CI -0.39, -0.19), irritative obstructive symptoms (-0.35SD 95%CI -0.47, -0.23), sexual function (-0.12SD 95%CI -0.24, -0.002), and bowel bother (-0.27SD 95%CI -0.42, -0.11). These patterns persisted up to the 5th year. High-intensity focused ultrasound and active surveillance only have results at 1st year, showing no statistically significant worsening. CONCLUSIONS: No remarkable differences in PRO appeared between modalities within each treatment. Nowadays, available evidence supports brachytherapy as possible alternative to radical prostatectomy for patients seeking an attempted curative treatment limiting the risk for urinary incontinence and sexual dysfunction.

Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial.

PURPOSE: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). PATIENTS AND METHODS: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. RESULTS: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. CONCLUSION: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.

High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial.

BACKGROUND: The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. METHODS: In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. FINDINGS: Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. INTERPRETATION: Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation. FUNDING: Spanish National Health Investigation Fund, AstraZeneca.

Permanent seed brachytherapy for clinically localized prostate cancer: long-term outcomes in a 700 patient cohort.

PURPOSE: Few large European studies have evaluated long-term outcomes for permanent prostate brachytherapy (PPB) as monotherapy for clinically localized prostate cancer. The objective of the present study was to evaluate long-term survival in this patient profile. METHODS AND MATERIALS: Retrospective study of 700 patients who underwent transperineal ultrasound-guided iodine-125 PPB (145 Gy) between January 2000 and July 2012. Median age was 64.8 years (range, 35-79). Most patients (638 of 700; 91%) had low-risk disease (D'Amico criteria). Eighty-five patients (12%) received hormonal treatment. Overall survival, cause-specific survival, and biochemical relapse-free survival were calculated and estimated using actuarial and Kaplan-Meier methods. Differences between groups were assessed using the log-rank test. RESULTS: Median followup was 63 months (range, 6-164). At 5- and 10-year followup, respectively, overall survival was 94% (95% confidence interval [CI], 92-96) and 84% (95% CI, 78-90); cause-specific survival was 100% and 97% (95% CI, 95-99); and biochemical relapse-free survival was 95% (95% CI, 93-97) and 85% (95% CI, 79-91). CONCLUSIONS: The long-term results presented in this report confirm previous studies and provide additional support for the use of PPB in patients with favorable-risk prostate cancer. Seed brachytherapy provides excellent long-term results in this patient profile.

External beam radiotherapy plus single-fraction high dose rate brachytherapy in the treatment of locally advanced prostate cancer.

PURPOSE: To evaluate the efficacy and toxicity of external beam radiation therapy (EBRT) plus high-dose-rate brachytherapy (HDRB) as a boost in patients (pts) with intermediate or high-risk prostate cancer. METHODS AND MATERIALS: From 2002 to July 2012, 377 pts with a diagnosis of intermediate or high-risk prostate cancer were treated with EBRT plus HDRB. Median patient age was 66 years (range, 41-86). Most patients (347 pts; 92%) were classified as high-risk (stage T2c-T3, or PSA>20 ng/mL, or GS ⩾ 8), with 30 patients (8%) considered intermediate risk. All patients underwent EBRT at a prescribed dose of 60.0 Gy (range, 45-70 Gy) to the prostate and seminal vesicles. A total of 120 pts (31%) received a dose of 46 Gy (45-50 Gy) to the true pelvis. All pts received a single-fraction 9 Gy (9-15 Gy) HDR boost. Most patients (353; 94%) were prescribed complete androgen deprivation therapy (ADT). Overall survival (OS), cause-specific survival (CSS), and biochemical relapse-free survival (BRFS) rates were calculated. In the case of BRFS, patients with <26 months of follow-up (n=106) were excluded to minimize the impact of ADT. RESULTS: The median follow-up for the entire sample was 50 months (range, 12-126), with 5-year actuarial OS and CSS, respectively, of 88% (95% confidence interval [CI]: 84-92) and 98% (95% CI: 97-99). The 5-year BRFS was 91% (95% CI: 87-95) in the 271 pts with ⩾ 26 months (median, 60 months) of follow-up. Late toxicity included grade 2 and 3 gastrointestinal toxicity in 17 (4.6%) and 6 pts (1.6%), respectively, as well as grades 2 and 3 genitourinary toxicity in 46 (12.2%) and 3 pts (0.8%), respectively. CONCLUSION: These long-term outcomes confirm that EBRT plus a single-fraction HDRB boost provides good results in treatment-related toxicity and biochemical control. In addition to the excellent clinical results, this fractionation schedule reduces physician workload, treatment-related expenses, patient discomfort and risks associated with anaesthesia. We believe these findings support the use of single-fractionation boost techniques.

Adaptation and validation of the Spanish version of the Patient-Oriented Prostate Utility Scale (PORPUS).

OBJECTIVE: The Patient-Oriented Prostate Utility Scale (PORPUS) is a combined profile and utility-based quality of life measure for prostate cancer patients. Our objectives were to adapt the PORPUS into Spanish and to assess its acceptability, reliability, and validity. METHODS: The PORPUS was adapted into Spanish using forward and back translations and cognitive debriefing. PORPUS was administered jointly with the SF-36 and the Expanded Prostate Index Composite (EPIC) to 480 Spanish prostate cancer patients treated with radical prostatectomy or radiotherapy. The Spanish PORPUS scores' distribution and reliability were examined and compared with the original instrument. To evaluate construct validity, relationships were assessed between PORPUS and other instruments (testing hypotheses of the original PORPUS study), and among known groups defined by side effect severity. RESULTS: Reliability coefficient was 0.76 (similar to the original PORPUS' 0.81). Spanish PORPUS items presented correlations ranging 0.57-0.88 with the corresponding EPIC domains, as in the original PORPUS study (0.60-0.83). Both PORPUS-P and PORPUS-U showed significant differences and large effect sizes (0.94-1.90) when comparing severe versus no problem groups on urinary, bowel, sexual and hormonal side effects defined by EPIC. CONCLUSIONS: A conceptually equivalent Spanish version was obtained, with high reliability and good construct validity, similar to the original Canadian PORPUS version. It can therefore be used to measure health-related quality of life and utilities in Spanish prostate cancer patients.

Quality of life impact of treatments for localized prostate cancer: cohort study with a 5 year follow-up.

PURPOSE: To assess long-term quality of life (QoL) impact of treatments in localized prostate cancer patients treated with radical prostatectomy, external beam radiotherapy or brachytherapy. MATERIAL AND METHODS: Observational, prospective cohort study with pre-treatment QoL evaluation and follow-up until five years after treatment. 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited in 2003-2005. QoL was measured by the EPIC questionnaire, with urinary irritative-obstructive, incontinence, bowel, sexual, and hormonal scores (ranging 0-100). RESULTS: Brachytherapy's QoL impact was restricted to the urinary domain, Generalized Estimating Equation models showed score changes at five years of -12.0 (95% CI=-15.0, -9.0) in incontinence and -5.3 (95% CI=-7.5, -3.1) in irritative-obstructive scales. Compared to brachytherapy, radical prostatectomy fared +3.3 (95% CI=+0.0, +6.5) points better in irritative-obstructive but -17.1 (95% CI=-22.7, -11.5) worse in incontinence. Sexual deterioration was observed in radical prostatectomy (-19.1; 95% CI=-25.1, -13.1) and external radiotherapy groups (-7.5; 95% CI=-12.5, -2.5). CONCLUSIONS: Brachytherapy is the treatment causing the least impact on QoL except for moderate urinary irritative-obstructive symptoms. Our study provides novel long-term valuable information for clinical decision making, supporting brachytherapy as a possible alternative to radical prostatectomy for patients seeking an attempted curative treatment, while limiting the risk for urinary incontinence and sexual impact on QoL.

Interobserver variability in target volume delineation in postoperative radiochemotherapy for gastric cancer. A pilot prospective study.

INTRODUCTION: The aim of this study is to determine the interobserver variability (IV) between radiation oncologists (RO) in target volume delineation for postoperative gastric cancer (GC) radiotherapy planning. MATERIALS AND METHODS: Four physicians were asked to delimitate clinical target volume (CTV) on the same 3D CT images in 9 postoperative radiochemotherapy GC patients. Instructions were given to include tumour bed, remaining stomach, anastomosis, duodenal loop and local lymph nodes. The principal variable was spatial volume discrepancy between the main observer (called "A") and other observers (all called "B"), which were compared using the mathematical formula A⌣B/A⌢B, applied to the 3D CT images using Boolean operators. Analysis of variance with two random effects (observers and patients) was performed. RESULTS: Mean volumes were 1410 cm(3) for OBA, 1231 cm(3) for OB2, 734.6 cm(3) for OB3 and 1350 cm(3) for OB4. Discrepancies were 519.9±431.6 cm(3) for OB2, 652.1±294.36 cm(3) for OB3 and 225.90±237.07 cm(3) for OB4. Standard deviation ascribed to patients as random effect was 898.6 cm(3) and that ascribed to observers was 198.10 cm(3), considered as a statistically significant difference. CONCLUSIONS: A significant IV in target delineation that can be attributed to many factors depends more on patients' characteristics than RO delineating decisions.

[Cost comparison of three treatments for localized prostate cancer in Spain: radical prostatectomy, prostate brachytherapy and external 3D conformal radiotherapy]. / Comparación de costes de tres tratamientos del cáncer de próstata localizado en España: prostatectomía radical, braquiterapia prostática y radioterapia conformacional externa 3D.

OBJECTIVE: To compare the initial costs of the three most established treatments for clinically localized prostate cancer according to risk, age and comorbidity groups, from the healthcare provider's perspective. METHODS: We carried out a cost comparison study in a sample of patients consecutively recruited between 2003 and 2005 from a functional unit for prostate cancer treatment in Catalonia (Spain). The use of services up to 6 months after the treatment start date was obtained from hospital databases and direct costs were estimated by micro-cost calculation. Information on the clinical characteristics of patients and treatments was collected prospectively. Costs were compared by using nonparametric tests comparing medians (Kruskall-Wallis) and a semi-logarithmic multiple regression model. RESULTS: Among the 398 patients included, the cost difference among treatments was statistically significant: medians were € 3,229.10, € 5,369.00 and € 6,265.60, respectively, for the groups of patients treated with external 3D conformal radiotherapy, brachytherapy and radical retropublic prostatectomy, (p<0.001). In the multivariate analysis (adjusted R(2)=0.8), the average costs of brachytherapy and external radiotherapy were significantly lower than that of prostatectomy (coefficient -0.212 and -0.729, respectively). CONCLUSIONS: Radical prostatectomy proved to be the most expensive treatment option. Overall, the estimated costs in our study were lower than those published elsewhere. Most of the costs were explained by the therapeutic option and neither comorbidity nor risk groups showed an effect on total costs independent of treatment.

Quality-of-life impact of primary treatments for localized prostate cancer in patients without hormonal treatment.

PURPOSE: Earlier studies evaluating the effect on quality of life (QoL) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy, which could have affected their outcomes. Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment. PATIENTS AND METHODS: This was a prospective study of 435 patients treated with radical prostatectomy, external-beam radiotherapy, or brachytherapy. QoL was assessed before and after treatment with the Short Form-36 and the Expanded Prostate Cancer Index Composite. Differences between groups were tested by analysis of variance. Distribution of outcome at 3 years was examined by stratifying according to baseline status. Generalized estimating equation models were constructed to assess the effect of treatment over time. RESULTS: Compared with the brachytherapy group, the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results (-18.22, -13.19, and +6.38, respectively, at 3 years; P < .001). In patients with urinary irritative-obstructive symptoms at baseline, improvement was observed in 64% of those treated with nerve-sparing radical prostatectomy. Higher bowel worsening (-2.87, P = .04) was observed in the external radiotherapy group, with 20% of patients reporting bowel symptoms. CONCLUSION: Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms. External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction. External radiotherapy also caused bowel adverse effects. Relevant differences between treatment groups persisted for up to 3 years of follow-up, although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up. These results provide valuable information for clinical decision making.

External beam radiotherapy plus high-dose-rate brachytherapy for treatment of locally advanced prostate cancer: the initial experience of the Catalan Institute of Oncology.

PURPOSE: The objective of this study was to report initial outcomes in patients with locally advanced prostate cancer (CaP) who underwent external beam radiation therapy (EBRT) treatment combined with high-dose-rate brachytherapy (HDR-BT) as a boost. METHODS AND MATERIALS: From 2002 to 2007, 114 CaP patients underwent EBRT followed by (192)I HDR-BT. The patients were classified into intermediate- (Group 1) or high- (Group 2) risk groups. The mean total EBRT dose was 60.0Gy (95% confidence interval [CI]: 59.9-60.1) at 2Gy per fraction. After a mean of 20.6 days (95% CI: 18.4-22.8), all the patients received a single-fraction 9-Gy dose of HDR-BT boost. Of the 114 patients in the study, 103 (90.4%) underwent up to 3 years of complete androgen deprivation therapy after diagnosis. RESULTS: The mean followup for the entire group was 32.1 months (95% CI: 29.9-34.4). The 4-year biochemical failure-free survival rate was 97.4% and treatment was well-tolerated. CONCLUSIONS: Preliminary biochemical control rates after EBRT plus one fraction of 9-Gy HDR-BT are encouraging. This atypical fractionation schedule is cost-effective and reduces patient discomfort and treatment-related risks. More followup is required to confirm these findings.

Twice-a-day radiotherapy for head and neck cancer: the Catalan Institute of Oncology experience.

PURPOSE: The purpose of this work is to evaluate the contribution of hyperfractionated radiotherapy (RT) in head and neck cancer by sub-localisation. PATIENTS AND METHODS: From 1992 to 1999, 318 patients with squamous head and neck tumours treated by hyperfraction RT were analysed according to their sub-localisation and stage. Fractions used were 1.2 Gy twice-a-day with a curative intent on all patients, to a total mean dose of 79.14 Gy. Treatment protocols by localisation were: larynx: 55 patients with T2N0 and T1-2N1 tumours treated with only RT and 27 patients with T3N0-1 in complete remission after three cycles of induction chemotherapy (ICT); hypopharynx: 29 patients with T2-4N0-2b resectable tumors in response to three cycles of ICT; oropharynx: 48 patients with T2-3N0-1 and T1N1 tumours treated with only RT; 34 patients with nasopharynx tumours treated with RT and three cycles of ICT if T4 or >N1; finally, 125 patients with non-surgical tumours of any localisation treated with four cycles of induction CT and RT. RESULTS: LARYNX: Actuarial local control (LC), disease-free survival (DFS) and overall survival (OS) at 5 years were 78, 73 and 48%, respectively, in T2 tumours and 75, 72 and 60% in stage III disease. HYPOPHARYNX: Actuarial LC, DFS and OS at 4 years were 44, 39 and 35%, respectively. OROPHARYNX: Actuarial LC, DFS and OS at 5 years were 52, 44 and 31%, respectively. NASOPHARYNX: Actuarial LC, DFS and OS at 5 years were 78, 72 and 78%, respectively. NON-SURGICAL TUMORS: Actuarial LC, DFS and OS at 5 years were 39, 33 and 19%, respectively. A total of 47 patients (14.8%) of the overall group had a second tumour, 72% of them tobacco-related. Only patients with nasopharynx tumours had a low incidence of second tumours. CONCLUSIONS: Twice-a-day external RT can be effectively managed in patients with head and neck cancer. Second neoplasm and intercurrent diseases become an important problem in low and medium stages whereas disease recurrences is the main problem in advanced stages. Results by localisation permit to obtain conclusions about their indications in each one.