Cancer detection and complications of transperineal prostate biopsy with antibiotics when indicated.

OBJECTIVES: To describe the prostate cancer (PCa) detection rate, including clinically significant prostate cancer (csPCa), in a large cohort of patients who underwent transperineal ultrasonography-guided systematic prostate biopsy (TPB-US) using a probe-mounted transperineal access system, with magnetic resonance imaging (MRI) cognitive fusion in case of a Prostate Imaging-Reporting and Data System grade 3-5 lesion, under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure-related complications with a cohort of patients undergoing transrectal ultrasonography-guided (TRB-US) and transrectal MRI-guided biopsies (TRB-MRI). PATIENTS AND METHODS: This was an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen level, clinical tumour stage, prostate volume, MRI parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure-related complications were assessed. csPCa was defined as ISUP grade ≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection. RESULTS: A total of 1288 TPB-US procedures were evaluated. The overall detection rate for PCa in biopsy-naive patients was 73%, and for csPCa it was 63%. The incidence of hospitalization was 1% in TPB-US (13/1288), compared to 4% in TRB-US (8/214) and 3% in TRB-MRI (7/219; P = 0.002). CONCLUSIONS: Contemporary combined systematic and target TPB-US with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure-related complications.

Increasing age is not associated with toxicity leading to discontinuation of treatment in patients with urothelial non-muscle-invasive bladder cancer randomised to receive 3 years of maintenance bacille Calmette-Guérin: results from European Organisation for Research and Treatment of Cancer Genito-Urinary Group study 30911.

OBJECTIVE: To determine the relationship of age to side-effects leading to discontinuation of treatment in patients with stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with maintenance bacille Calmette-Guérin (BCG). PATIENTS AND METHODS: We evaluated toxicity for 487 eligible patients with intermediate- or high-risk Ta-T1 (without carcinoma in situ) NMIBC randomised to receive 3 years of maintenance BCG therapy (247 BCG alone and 240 BCG + isoniazid) in European Organisation for Research and Treatment of Cancer Genito-Urinary Group trial 30911. The percentage of patients who stopped for toxicity and the number of treatment cycles that they received were compared in four age groups, ≤60, 61-70, 71-75 and >75 years, using the Mantel-Haenszel chi-square test for trend. RESULTS: The percentage of patients stopping BCG for toxicity was 17.9% in patients aged ≤60 years, 21.9% in patients aged 61-70 years, 22.9% in patients aged 71-75 years, and 16.4% in patients aged >75 years (P = 0.90). For both systemic and local side-effects, there was likewise no significant difference. CONCLUSION: In patients with intermediate- and high-risk Ta-T1 NMIBC treated with BCG, no differences in toxicity as a reason for stopping treatment were detected based on patient age.

Effect of a comprehensive surgical safety system on patient outcomes.

BACKGROUND: Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway. METHODS: We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals. RESULTS: In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals. CONCLUSIONS: Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care. (Netherlands Trial Register number, NTR1943.).

Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial.

BACKGROUND: A survival benefit was demonstrated for patients with low-volume metastatic prostate cancer (mPCa) when local radiotherapy was added to androgen deprivation therapy (ADT). OBJECTIVE: To determine the effect of ADT combined with external beam radiotherapy (EBRT) to the prostate on health-related quality of life (HRQoL) of patients with primary bone mPCa. DESIGN, SETTING, AND PARTICIPANTS: The HORRAD trial is a multicentre randomised controlled trial recruiting 432patients with primary bone mPCa between 2004 and 2014. INTERVENTION: Patients were randomised to ADT with EBRT or to ADT alone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed two validated HRQoL questionnaires (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core Module (QLQ-C30) and EORTC Quality of Life Questionnaire Prostate Module [QLQ-PR25]) at baseline and at 3, 6, 12, and24 mo after the initiation of treatment. The effect of both treatments was evaluated based on mixed-effect models. RESULTS AND LIMITATIONS: Patient characteristics and HRQoL scores at baseline were similar in both arms. At baseline, 98% of patients completed the questionnaires, compared with 58% at 24 mo. Patients reported significantly more diarrhoea (difference between the groups 10.8; 95% confidence interval [CI] 7.3-14.2), bowel symptoms (4.5; 95% CI 2.1-6.8), and urinary symptoms (11.9; 95% CI 8.9-14.8) after EBRT and ADT compared with ADT alone (all between-arm difference p < 0.001). Urinary complaints levelled at 6 mo. At 2 yr, only bowel symptom scores were significantly different (8.0; 95% CI 4.8-11.1, p ≤ 0.001), but 68% of patients in the radiotherapy group did not report clinically relevant worsening of their bowel symptom scores. CONCLUSIONS: Patients with bone mPCa reported temporary modest urinary and bowel symptoms after combined treatment with EBRT of the prostate and ADT compared with ADT alone. For some patients (22%), deterioration of bowel functions remains at 2 yr, whereas general HRQoL does not deteriorate.. PATIENT SUMMARY: This study investigated the effect of radiotherapy to the prostate added to hormonal therapy on patient-reported health-related quality of life (HRQoL) in patients with primary bone metastatic prostate cancer. Most patients reported only temporary urinary and bowel symptoms. In 22% of patients, bowel symptoms remained at 2 yr, whereas general HRQoL did not deteriorate.

Variation in the Prescription of Androgen Deprivation Therapy in Intermediate- and High-risk Prostate Cancer Patients Treated with Radiotherapy in the Netherlands, and Adherence to European Association of Urology Guidelines: A Population-based Study.

BACKGROUND: According to (inter-)national guidelines, (neo-)adjuvant and concurrent androgen deprivation therapy (ADT) in combination with external beam radiotherapy (EBRT) is optional for intermediate-risk prostate cancer (PCa) patients and is the recommended standard treatment for high-risk PCa patients. OBJECTIVE: The aim of this study is to provide insight into the prescription of ADT in intermediate- and high-risk PCa patients treated with EBRT in the Netherlands, and to evaluate adherence to European Association of Urology guidelines and factors affecting prescription. DESIGN, SETTING, AND PARTICIPANTS: All intermediate- and high-risk PCa patients between October 2015 and April 2016 were identified through the population-based Netherlands Cancer Registry. Variation in the prescription of ADT in patients with EBRT was evaluated. Multivariable multilevel logistic regression analyses were performed to determine the probability of ADT and to examine the role of patient-, tumour-, and hospital-related factors. RESULTS AND LIMITATIONS: Overall, 29% of patients with intermediate-risk PCa received ADT varying from 3% to 73% between institutions. From the multivariable regression analysis, higher Gleason grade, magnetic resonance imaging, and computed tomography (CT)-positron-emission tomography/CT prior to radiotherapy appeared to be associated with increased prescription of ADT. Among high-risk patients, 83% received ADT, varying from 57% to 100% between departments. A higher prostate-specific antigen level, more advanced tumour stage, and a higher Gleason grade were associated with increased prescription. CONCLUSIONS: Less than one-third of intermediate-risk PCa patients treated with EBRT receive ADT. The variation in the prescription of ADT between different institutions is substantial. This suggests that the prescription is largely dependent on different institutional policies. The guideline adherence in high-risk PCa is fairly good, as the vast majority of patients received ADT as recommended. However, given the clear recommendations in the guidelines, adherence could be improved. PATIENT SUMMARY: In this review, we looked at the variation of hormonal treatment in intermediate- and high-risk prostate cancer patients. We found substantial variation between institutions.

The Feasibility and Utility of Cystoscopy-Guided Hydrogel Marker Placement in Patients With Muscle-Invasive Bladder Cancer.

PURPOSE: Fiducial markers at the borders of bladder tumors are useful to facilitate target delineation radiation therapy (RT) and offer the possibility of image guided RT for a focal boost. Our purpose was to evaluate the feasibility and technical performance of cystoscopy-guided placement of hydrogel markers in patients with bladder cancer referred for RT. METHODS AND MATERIALS: Ours was a prospective, multicenter, feasibility, and utility study. Thirty-two consecutive patients with muscle-invasive bladder cancer, referred for RT, underwent cystoscopy-guided implantation of hydrogel markers. Feasibility, clinical performance of the markers, and adverse events were registered. Computer tomography (CT) scans and cone beam CT (CBCT) scans acquired during RT were analyzed to evaluate the visibility and stability of the markers during the radiation period. RESULTS: A total of 107 hydrogel spots were implanted in 32 patients with bladder cancer. There were no procedure-related adverse events. On the simulation CT scan 76.6% of the implanted markers were sufficient for tumor delineation. At start of treatment 52.3% were visible on the CBCT and adequate for positional verification on a routine basis. The washout rate during treatment was 9.3%. At the end of treatment 46.7% of implanted spots were visible on CBCT scan and adequate for routine positional verification. At patient level, in 31.2% of cases, use of hydrogel fiducials showed adequate performance throughout the whole course. CONCLUSIONS: Cystoscopy-guided placement of hydrogel markers is both safe and feasible for muscle-invasive bladder tumors. Adequate performance for radiation purposes throughout the whole course (implantation, delineation, and positional verification) was 46.7% of all implanted markers, leaving room for improvement.

Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial.

BACKGROUND: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. OBJECTIVE: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. DESIGN, SETTING, AND PARTICIPANTS: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20ng/ml and primary bone mPCa on bone scan between 2004 and 2014. INTERVENTION: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. RESULTS AND LIMITATIONS: Median PSA level was 142ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4-49.6) in the radiotherapy group and 43 mo (95% CI: 32.6-53.4) in the control group (p=0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70-1.14; p=0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8-18.2), compared with 12 mo (95% CI: 10.6-13.4) in the control group. The crude HR (0.78; 95% CI: 0.63-0.97) was statistically significant (p=0.02). CONCLUSIONS: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. PATIENT SUMMARY: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. TWITTER SUMMARY: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival.

Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis.

BACKGROUND: Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: To systematically review trials of prostate radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known. We searched extensively for eligible trials and asked investigators when results would be available. We could then anticipate that a definitive meta-analysis of the effects of prostate radiotherapy was possible. We obtained prepublication, unpublished, and harmonised results from investigators. INTERVENTION: We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for the effects of prostate radiotherapy on survival, progression-free survival (PFS), failure-free survival (FFS), biochemical progression, and subgroup interactions were combined using fixed-effect meta-analysis. RESULTS AND LIMITATIONS: We identified one ongoing (PEACE-1) and two completed (HORRAD and STAMPEDE) eligible trials. Pooled results of the latter (2126 men; 90% of those eligible) showed no overall improvement in survival (HR=0.92, 95% confidence interval [CI] 0.81-1.04, p=0.195) or PFS (HR=0.94, 95% CI 0.84-1.05, p=0.238) with prostate radiotherapy. There was an overall improvement in biochemical progression (HR=0.74, 95% CI 0.67-0.82, p=0.94×10-8) and FFS (HR=0.76, 95% CI 0.69-0.84, p=0.64×10-7), equivalent to ∼10% benefit at 3yr. The effect of prostate radiotherapy varied by metastatic burden-a pattern consistent across trials and outcome measures, including survival (<5, ≥5; interaction HR=1.47, 95% CI 1.11-1.94, p=0.007). There was 7% improvement in 3-yr survival in men with fewer than five bone metastases. CONCLUSIONS: Prostate radiotherapy should be considered for men with mHSPC with a low metastatic burden. PATIENT SUMMARY: Prostate cancer that has spread to other parts of the body (metastases) is usually treated with hormone therapy. In men with fewer than five bone metastases, addition of prostate radiotherapy helped them live longer and should be considered.

Immediate treatment vs. active-surveillance in very-low-risk prostate cancer: the role of patient-, tumour-, and hospital-related factors.

BACKGROUND: To provide insight in the treatment variation of very-low-risk prostate cancer patients and to assess the role of hospital-related factors. METHODS: All patients diagnosed with very-low-risk prostate cancer (cT1c-cT2a, PSA < 10 ng/ml, Gleason score <7 and <3 positive cores) in 2015 and 2016 were identified through the population-based Netherlands Cancer Registry. Multilevel logistic regression analyses were performed to examine the crude and case-mix adjusted probability of immediate treatment vs. active-surveillance (AS) according to hospital of diagnosis and to evaluate the effect of patient-, tumour-, and hospital-related factors. RESULTS: In all, 2047 (85.4%) of the 2396 patients with very-low-risk prostate cancer were managed with AS. The crude proportion of patients with AS varied from 33.3 to 100% between hospitals. Case-mix adjusted probability varied from 71 to 97%. Tumour stage cT2a vs. cT1c (OR 2.0, 95%CI 1.1-3.6), two vs. one positive core (OR 2.8, 95%CI 1.6-4.7), diagnostic MRI (OR 2.8, 95%CI 1.5-5.2), discussion of a patient in a multi-disciplinary team (OR 2.2, 95%CI 1.1-4.5), discussion of treatment options with the patient (OR 3.3, 95%CI 1.5-7.4) and type of hospital (non-university referral hospital vs. community hospital: OR 0.5, 95%CI 0.2-0.9) were associated with immediate treatment. CONCLUSION: The majority of Dutch very-low-risk prostate cancer patients is managed with AS but variation between hospitals exists. Part of the variation is explained by patient- and tumour characteristics but also hospital-related factors play a role. This implies that clinical practice could be improved.

Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas.

A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

Treatment decision making in prostate cancer: patients' participation in complex decisions.

OBJECTIVE: (1) To explore to what degree prostate cancer (PC) patients felt they had participated in treatment decision making (TDM). (2) To determine whether perceived roles during TDM were associated with medical and sociodemographic variables. (3) To examine to what extent satisfaction with TDM was related to perceived role or medical and sociodemographic variables. METHODS: Patients (n=126) were recruited in hospitals and from the Dutch PC patient organization. The relationship between patients' role and stage of disease, treatment modality, age, social status and education was determined, as well as patients' satisfaction with TDM. RESULTS: Most patients felt they had participated in TDM (autonomous 18%, collaborative 60%). Older patients and those with advanced disease more frequently reported not having been involved in decision making. Satisfaction with TDM was related to age and role in TDM but not to stage of disease or treatment modality. Younger men were least content when they had not been involved in decision making. CONCLUSION: Patients' level of participation and satisfaction with TDM appears to be related to medical and sociodemographic variables. PRACTICE IMPLICATIONS: Satisfaction with TDM may be related to patients' age and assumed role. It is recommended to take this into account when planning treatment for prostate cancer patients.

Pseudomelanosis of the bladder: a case report.

BACKGROUND: Pseudomelanosis is due to deposition of pseudomelanin and is best known as the entity pseudomelanosis coli. However, pseudomelanosis in the urinary tract has never been described. Pigmentation of the urothelium, known as melanosis vesica, is characterized by deposition of melanin pigment granules without signs of atypia. Simple (true) melanosis of the bladder is uncommon. CASE: A 52-year-old man presented with macroscopic hematuria. Cystoscopy and microscopic evaluation revealed pigmentation of the bladder urothelium diagnosed as pseudomelanosis vesica due to deposits of melaninlike pigment in the absence of detectable melanocytes and detectable by urine cytology. CONCLUSION: Pseudomelanosis vesica is a benign lesion that has never before been observed in the urinary tract.

EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guérin.

BACKGROUND: There are no prognostic factor publications on stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with 1-3 yr of maintenance bacillus Calmette-Guérin (BCG). OBJECTIVE: To determine prognostic factors in NMIBC patients treated with 1-3 yr of BCG after transurethral resection of the bladder (TURB), to derive nomograms and risk groups, and to identify high-risk patients who should be considered for early cystectomy. DESIGN, SETTING, AND PARTICIPANTS: Data for 1812 patients were merged from two European Organization for Research and Treatment of Cancer randomized phase 3 trials in intermediate- and high-risk NMIBC. INTERVENTION: Patients received 1-3 yr of maintenance BCG after TURB and induction BCG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prognostic factors for risk of early recurrence and times to late recurrence, progression, and death were identified in a training data set using multivariable models and applied to a validation data set. RESULTS AND LIMITATIONS: With a median follow-up of 7.4 yr, 762 patients recurred; 173 progressed; and 520 died, 83 due to bladder cancer (BCa). Statistically significant prognostic factors identified by multivariable analyses were prior recurrence rate and number of tumors for recurrence, and tumor stage and grade for progression and death due to BCa. T1G3 patients do poorly, with 1- and 5-yr disease-progression rates of 11.4% and 19.8%, respectively, and 1- and 5-yr disease-specific death rates of 4.8% and 11.3%. Limitations include lack of repeat transurethral resection in high-risk patients and exclusion of patients with carcinoma in situ. CONCLUSIONS: NMIBC patients treated with 1-3 yr of maintenance BCG have a heterogeneous prognosis. Patients at high risk of recurrence and/or progression do poorly on currently recommended maintenance schedules. Alternative treatments are urgently required. PATIENT SUMMARY: Non-muscle-invasive bladder cancer patients at high risk of recurrence and/or progression do poorly on currently recommended bacillus Calmette-Guérin maintenance schedules, and alternative treatments are urgently required. TRIAL REGISTRATION: Study 30911 was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911). Study 30962 was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.

Is baseline quality of life useful for predicting survival with hormone-refractory prostate cancer? A pooled analysis of three studies of the European Organisation for Research and Treatment of Cancer Genitourinary Group.

PURPOSE: Patients with symptomatic metastatic hormone-resistant prostate cancer (HRPC) survive a median of 10 months and are often regarded as a homogeneous group. Few prognostic factors have been identified so far. We examined whether baseline health-related quality of life (HRQOL) parameters assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) were independent prognostic factors of survival and whether they bring extra precision to the predictions achievable with models based on clinical and biochemical factors only. PATIENTS AND METHODS: Data of 391 symptomatic (bone) metastatic HRPC patients from three randomized EORTC trials were used in multivariate Cox proportional hazards models. The significance level was set at alpha =.05. RESULTS: Of the 391 patients, 371 died, most of prostate cancer. Bone scan result, performance status, hemoglobin level, and insomnia and appetite loss as measured by the EORTC QLQ-C30 were independent predictors of survival. This model's area under the receiver operating curve was 0.65 compared with 0.63 without the two HRQOL factors. CONCLUSION: Certain HRQOL sores, at baseline, seem to be predictors for duration of survival in HRPC. However, such measurements do not add to the predictive ability of models based only on clinical and biochemical factors.

Psychosocial and educational aspects in prostate cancer patients.

Prostate cancer was a neglected area in psycho-oncology. There is now a growing number of studies on the psychosocial aspects of having prostate cancer and the possibilities to reduce these problems in educational and group interventions. In this issue of Patient Education and Counseling, studies are presented on several psychosocial and educational aspects in prostate cancer patients: screening events and outcomes, assessing the unmet information, support and care delivery needs, reacting to the diagnosis of prostate cancer, informational needs of men on hormonal therapy, changes in health-related quality of life three months after the diagnosis, information-seeking behaviors and information needs of partners, quality of leaflets, video information in decision making, and patient perceptions and priorities in a rehabilitation program. Conclusions are presented on neglected research areas in psychosocial and educational aspects of living with prostate cancer.

Changes in health-related quality of life of men with prostate cancer 3 months after diagnosis: the role of psychosocial factors and comparisment with benign prostate hyperplasia patients.

The objective of the pilot study is to measure the changes in health-related quality of life (HRQOL, general and prostate specific) 3 months after the disease has been diagnosed in men with prostate cancer. The results are compared with benign prostate hyperplasia (BPH) patients. Also the influence of psychosocial factors (distress, coping and social support) on the experienced changes in health-related quality of life is studied for both patient groups. The sample consists of 61 patients who filled in the questionnaire before the diagnosis was know to them and after 3 months (38 benign prostate hyperplasia and 23 prostate cancer patients). The measures consist of: quality of life, micturation symptoms, sexual functioning, coping style, psychological distress, life events, social support, social desirability, and health behavior. The results show a decrease in quality of life for prostate cancer patient after three moments, while the quality of life measure for BPH patients are stable over time. For both patient groups, the psychosocial factors do not change after 3 months. The psychosocial factors contribute only marginal to the changes in quality of life. Conclusions are drawn concerning the need and the content of psychosocial support and education for prostate cancer patients.

Side effects of Bacillus Calmette-Guérin (BCG) in the treatment of intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder: results of the EORTC genito-urinary cancers group randomised phase 3 study comparing one-third dose with full dose and 1 year with 3 years of maintenance BCG.

BACKGROUND: Although bacillus Calmette-Guérin (BCG) has proven highly effective in non-muscle-invasive bladder cancer (NMIBC), but it can cause severe local and systemic side effects. OBJECTIVES: The objective was to determine whether reducing the dose or duration of BCG was associated with fewer side effects. Efficacy comparisons of one-third dose versus full dose BCG given for 1 yr versus 3 yr have previously been published. DESIGN, SETTING, AND PARTICIPANTS: After transurethral resection, patients with intermediate- and high-risk NMIBC without carcinoma in situ were randomised to one-third dose or full dose BCG and 1 yr or 3 yr of maintenance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Local and systemic side effects were recorded at every instillation and divided into three time periods: during induction, during the first year after induction, and during the second and third years of maintenance. RESULTS AND LIMITATIONS: Of the 1316 patients who started BCG, 826 (62.8%) reported local side effects, 403 (30.6%) reported systemic side effects, and 914 (69.5%) reported local or systemic side effects. The percentage of patients with at least one side effect was similar in the four treatment arms (p=0.41), both overall and in the different time periods. The most frequent local and systemic side effects were chemical cystitis in 460 (35.0%) patients and general malaise in 204 patients (15.5%); 103 patients (7.8%) stopped treatment because of side effects. No significant difference was seen between treatment groups (p=0.74). In the 653 patients randomised to 3 yr of BCG, 35 (5.4%) stopped during the first year, and 21 (3.2%) stopped in the second or third year. CONCLUSIONS: No significant differences in side effects were detected according to dose or duration of BCG treatment in the four arms. Side effects requiring stoppage of treatment were seen more frequently in the first year, so not all patients are able to receive the 1-3 yr of treatment recommended in current guidelines. This study was registered at ClinicalTrials.gov with identifier NCT00002990 (http://clinicaltrials.gov/ct2/show/record/NCT00002990).

The effect of age on the efficacy of maintenance bacillus Calmette-Guérin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911.

BACKGROUND: Although maintenance bacillus Calmette-Guérin (BCG) is the recommended treatment in high-risk non-muscle-invasive bladder cancer (NMIBC), its efficacy in older patients is controversial. OBJECTIVE: To determine the effect of age on prognosis and treatment outcome in patients with stage Ta T1 NMIBC treated with maintenance BCG. DESIGN, SETTING, AND PARTICIPANTS: A total of 957 patients with intermediate- or high-risk Ta T1 (without carcinoma in situ) NMIBC were randomized in European Organization for Research and Treatment of Cancer (EORTC) trial 30911 comparing six weekly instillations of epirubicin, BCG, and BCG plus isoniazid followed by three weekly maintenance instillations over 3 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox multivariate proportional hazards regression models were used to assess the relative importance of age for recurrence, progression, overall survival, and NMIBC-specific survival with adjustment for EORTC risk scores. RESULTS AND LIMITATIONS: Overall, 822 eligible patients were included: 546 patients in the BCG with or without INH arms and 276 in the epirubicin arm. In patients treated with BCG with or without INH, 34.1% were >70 yr of age and 3.7% were >80 yr. With a median follow-up of 9.2 yr, patients >70 yr had a shorter time to progression (p=0.028), overall survival (p<0.001), and NMIBC-specific survival (p=0.049) after adjustment for EORTC risk scores in the multivariate analysis. The time to recurrence was similar compared with the younger patients. BCG was more effective than epirubicin for all four end points considered, and there was no evidence that BCG was any less effective compared with epirubicin in patients >70 yr. CONCLUSIONS: In intermediate- and high-risk Ta T1 urothelial bladder cancer patients treated with BCG, patients >70 yr of age have a worse long-term prognosis; however, BCG is more effective than epirubicin independent of patient age. PATIENT SUMMARY: Intravesical bacillus Calmette-Guérin for non-muscle-invasive bladder cancer is less effective in patients >70 yr of age, but it is still more effective than epirubicin. TRIAL REGISTRATION: This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911; http://www.cancer.gov/clinicaltrials/search/view?cdrid=77075&version=HealthProfessional&protocolsearchid=12442243#StudyIdInfo_CDR0000077075).

Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance.

BACKGROUND: The optimal dose and duration of intravesical bacillus Calmette-Guérin (BCG) in the treatment of non-muscle-invasive bladder cancer (NMIBC) are controversial. OBJECTIVE: To determine if a one-third dose (1/3D) is not inferior to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of maintenance, and if 1/3D and 1 yr of maintenance are associated with less toxicity. DESIGN, SETTING, AND PARTICIPANTS: After transurethral resection, intermediate- and high-risk NMIBC patients were randomized to one of four BCG groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The trial was designed as a noninferiority study with the null hypothesis of a 10% decrease in the disease-free rate at 5 yr. Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model. RESULTS AND LIMITATIONS: In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr, there were no significant differences in toxicity between 1/3D and FD. The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected. We found that 1/3D-1 yr is suboptimal compared with FD-3 yr (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.59-0.94; p=0.01). Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG. In high-risk patients, 3 yr is associated with a reduction in recurrence (HR: 1.61; 95% CI, 1.13-2.30; p=0.009) but only when given at FD. There were no differences in progression or survival. CONCLUSIONS: There were no differences in toxicity between 1/3D and FD. Intermediate-risk patients should be treated with FD-1 yr. In high-risk patients, FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths. The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.

An international field study of the EORTC QLQ-PR25: a questionnaire for assessing the health-related quality of life of patients with prostate cancer.

AIM: To evaluate the psychometrics of the EORTC QLQ-PR25, a questionnaire assessing the health-related quality of life of prostate cancer patients. METHODS: The QLQ-PR25 and the QLQ-C30 were administered to 642 prostate cancer patients from 13 countries treated with curative or palliative intent. The QLQ-PR25 assesses urinary, bowel and sexual symptoms and functioning, and the side-effects of hormonal treatment. RESULTS: Five hundred and nine patients were available for the final analysis. Multitrait scaling analyses confirmed the hypothesised scale structure of the QLQ-PR25. Internal consistency reliability was good (coefficient alpha=0.70-0.86) for the urinary symptoms and sexual function scales, but lower for the bowel function and side-effects of hormonal treatment scales (alpha<0.70). The module discriminated clearly between clinically distinct patient subgroups, and was responsive to changes in health status over time. CONCLUSION: In general, the QLQ-PR25 demonstrates acceptable psychometric properties and clinical validity. Some caution should be used in interpreting the bowel function and side-effects of hormonal therapy scales; results can be reported at the individual item and scale level.