Ana Boladeras

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.

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.

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 Brachytherapys 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.

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.

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.

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 providers 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.

Cost comparison of three treatments for localized prostate cancer in Spain: radical prostatectomy, prostate brachytherapy and external 3D conformal radiotherapy

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: Cost comparison study on a sample of patients recruited consecutively between 2003 and 2005 in a functional unit of treatment for prostate cancer in Catalonia. The use of services until 6 months after the treatment start date was obtained from hospital databases and direct costs were estimated by micro-cost calculation. The collection of information on clinical characteristics of patients and treatments was conducted prospectively. The costs were compared using nonparametric test comparing medians (Kruskal-Wallis) and a semi-logarithmic model of multiple regressions.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 Radical Retropubic Prostatectomy, Brachytherapy and External 3D Conformal Radiotherapy (P Conclusions: Radical prostatectomy proved to be the most expensive treatment option. Overall, the estimated costs in our study are lower than those published elsewhere. Therapeutic option explains most of the costs, and neither comorbidity nor risk group showed an independent effect from treatment on total costs.

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

IntroductionThe 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 methodsFour 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.ResultsMean volumes were 1410 cm3 for OBA, 1231 cm3 for OB2, 734.6 cm3 for OB3 and 1350 cm3 for OB4. Discrepancies were 519.9±431.6 cm3 for OB2, 652.1±294.36 cm3 for OB3 and 225.90±237.07 cm3 for OB4. Standard deviation ascribed to patients as random effect was 898.6 cm3 and that ascribed to observers was 198.10 cm3, considered as a statistically significant difference.ConclusionsA significant IV in target delineation that can be attributed to many factors depends more on patients’ characteristics than RO delineating decisions.

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.

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.