Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14).

BACKGROUND: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS). MATERIALS AND METHODS: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis. RESULTS: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse. CONCLUSION: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.

Postoperative pain in a prospectively assessed surgical short-stay cohort: A subgroup analysis.

BACKGROUND: There is sparse information about postoperative pain after short stay surgery. We explored the incidence of immediate postoperative pain and its relationship with persistent pain or opioid use 2 weeks after surgery. METHODS: This was a subgroup analysis of prospective and controlled data from adult patients (n = 931) who underwent short-stay surgery in a tertiary care hospital. Data comprised patient demographics, surgical category, pain scores and analgesic management during the recovery unit stay, before discharge on the postoperative morning after surgery and again 2 weeks after surgery. RESULTS: Half of the patients had severe dynamic pain in the recovery unit. It was commonest after orthopaedic (70% of patients), followed by gynaecological (54%), gastrointestinal (51%) and spine surgery (49%). Multimodal pain management was used for most patients (n = 811, 87%) with opioid use predominant. The median oxycodone dose during short-stay was the highest after orthopaedic surgery (39 mg). The first individual dynamic pain score after surgery was associated with follow-up pain score at rest (OR = 1.37), dynamic pain (OR = 1.35) and pain interference (OR = 1.34) at 2 weeks after surgery. Maximum dynamic pain reported in the recovery unit was associated with pain at rest (OR = 1.56), dynamic pain (OR = 1.65) and pain interference (OR = 1.45) at 2 weeks after surgery. Pain scores at 2 weeks were highest and analgesic use greatest in those patients who underwent spinal surgery. CONCLUSIONS: Intense postoperative pain remains common after short-stay surgery in some surgical categories including orthopaedic surgery and is associated with a greater likelihood of pain at 2 weeks.

Patient functional recovery after a 23-h surgery - a prospective, follow-up study.

PURPOSE: We evaluated patients' functional outcomes 2 weeks after a 23-h surgery model in a tertiary care hospital. METHODS: This prospective study comprised data on 993 consecutive adult patients who underwent a 23-h surgery. Patients were interviewed before surgery and at 14 days after surgery by telephone with a multidimensional structural survey including closed- and open-ended questions. Regarding functional outcomes, the patients were asked to assess their general wellbeing, energy levels and activities of daily living on a 5-point numeric rating scale (1 = poor to 5 = excellent). Data on patient characteristics, medical history, alcohol use, smoking status and pre-, peri- and postoperative pain and satisfaction with the care received were collected and analysed to determine whether these factors contributed to their recovery. The primary outcome measure was patient functional recovery at 14 days after surgery. RESULTS: Most patients reported moderate to excellent functional outcomes: 93.6% (95% CI, 92.1--95.1) of the patients showed a score ≥ 3 on the 5-point numeric scale. One out of four patients (23%) scored all three domains as excellent. A weak inverse correlation was noted between functional recovery and most pain in the 23-h postanaesthesia care unit as well as pain at 2 weeks after surgery. A weak positive correlation was noted between functional recovery and patient satisfaction with the instructions at discharge. CONCLUSIONS: Most patients showed ample functional recovery at 14 days after the 23-h surgery. Higher pain scores in the postanaesthesia care unit and 2 weeks after surgery predicted poor functional outcomes, and satisfaction with postoperative counselling predicted better outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04142203.

Awareness of Smoking as a Risk Factor in Bladder Cancer: Results from the Prospective FinnBladder 9 Trial.

BACKGROUND: Data regarding patient education and smoking habits among bladder cancer patients are scarce. OBJECTIVE: To investigate awareness of smoking as a risk factor for bladder cancer among bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: This is a substudy of a prospective, randomized, multicenter phase 3 trial (FinnBladder 9, NCT01675219). The data were collected at baseline and after 12 mo of follow-up between 2012 and 2020. INTERVENTION: Patients completed a comprehensive nonvalidated questionnaire on smoking in relation to bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measured were patient-reported awareness of smoking as a risk factor for bladder cancer, and the effect of smoking on bladder cancer-related recurrence, progression, and death. Parametric data were compared using Student's t test and proportions using Fischer's exact test. Factors affecting baseline awareness of the effect of smoking cessation on bladder cancer were studied using logistic regression. RESULTS AND LIMITATIONS: Of the 411 patients randomized, 370 completed the baseline questionnaire and were included in the analysis. At baseline, 44% of patients were uncertain if smoking was a risk factor for bladder cancer. Patient awareness of the fact that smoking cessation reduces the risk of bladder cancer recurrence increased from 86% to 92% after 12 mo of follow-up (p = 0.038). Older patients and patients with recurrent bladder cancer had significantly less knowledge about the effect of smoking on bladder cancer recurrence, progression, and mortality. A major limitation is that the response rate was lower at the 12-mo follow-up visit than at baseline. CONCLUSIONS: Awareness of smoking as a bladder cancer risk factor is low. Older patients and patients with recurrent bladder cancer may need special attention regarding education. PATIENT SUMMARY: We looked at outcomes for smoking-related patient education on bladder cancer in a Finnish population. We conclude that older patients and patients with recurrent bladder cancer may need to be educated on this subject.

Repeated 5-aminolevulinic Acid Instillations During Follow-up in Non-muscle-invasive Bladder Cancer: A Randomized Study.

BACKGROUND/AIM: Non-muscle invasive bladder carcinoma (NMIBC) is highly recurrent. We studied if 5-aminolevulinic acid (5-ALA) instillations before transurethral resection of bladder tumours (TURBT) and cystoscopy extend the time to recurrence during follow-up with NMIBC patients. PATIENTS AND METHODS: A prospective multicenter study enrolled 328 NMIBC patients. All TURBTs and control cystoscopies during the one-year study period were done with or without 5-ALA instillations. The primary endpoint was time to recurrence. The secondary endpoints were time to recurrence after 7.5, 10.5, and 13.5 months and the number of patients with progressive disease. RESULTS: The overall median follow-up time was 80.4 and 87.0 months for the control and study groups, respectively. There was no statistical difference in time to first recurrence between the two groups. CONCLUSION: We could not obtain significant differences between the control and 5-ALA groups in tumour recurrence among patients with NMIBC.

Stereotactic body radiotherapy for localized prostate cancer - 5-year efficacy results.

BACKGROUND: The use of stereotactic body radiotherapy (SBRT) as the primary treatment modality in clinically localized prostate cancer (PCa) is emerging. The aim of the study was to analyze the long-term results of PCa patients treated with SBRT. METHODS: This non-selected, real-life patient cohort included 213 patients with localized PCa treated with a robotic SBRT device during 2012-2015. RESULTS: The median follow-up was 64 months (range, 10-85 months), and all risk-groups were represented as 47 (22.1%), 56 (26.3%) and 110 (51.6%) patients were classified into D'Amico risk stratification of low, intermediate and high-risk groups, respectively. Androgen deprivation therapy (ADT) was administered to 64.3% of the patients. At cut-off, the biochemical relapse-free survival (bRFS) was 100, 87.5 and 80.0% for patients at low, intermediate and high-risk (p = 0.004), and 92.5, 84.2 and 66.7% for patients with Gleason score ≤ 6, 7 and ≥ 8, respectively (p = 0.001). The actuarial 5-year overall survival (OS) rates were 97.9, 96.4 and 88.6% in the low, intermediate and high-risk groups, respectively, and at the cut-off, the disease-specific survival (DSS) rate of the whole cohort was high (99.1%), as only two high-risk patients died due to PCa. CONCLUSION: Our present results of SBRT delivered with CyberKnife produced excellent long-term bRFS, OS and DSS outcomes among patients with localized PCa. We conclude that SBRT provides an efficient and convenient treatment option for patients with localized PCa, irrespective of the risk-group.

Cellular hyaluronan is associated with a poor prognosis in renal cell carcinoma.

PURPOSE: Hyaluronan, a major glycosaminoglycan of the extracellular matrix, can act as an oncogenic component of the tumor microenvironment in many human malignancies. We characterized the hyaluronan content of renal cell carcinomas (RCCs) and investigated its correlations with clinicopathological parameters and patient survival. PATIENTS AND METHODS: This retrospective study included data from 316 patients that had undergone surgery for RCC in Kuopio University Hospital in 2000 to 2013. The hyaluronan content of surgical tumor samples were histochemically stained with a biotinylated hyaluronan-specific affinity probe. The amount of tumor infiltrating lymphocytes was evaluated in each tumor. Kaplan-Meier and univariate and multivariate Cox-regression analyses were performed to estimate the impact of hyaluronan content on overall survival, disease-specific survival, and metastasis-free survival. RESULTS: Detectable cellular hyaluronan was associated with higher tumor grades and the presence of tumor infiltrating lymphocytes. Cellular hyaluronan identified a prognostically unfavourable subgroup among low-grade carcinomas. Multivariate analyses showed that measurable cellular hyaluronan was an independent negative prognostic factor for overall survival (hazard ratio [HR] 1.4; 95% confidence interval [CI]: 1.02-2.0; P = 0.039), Disease-specific survival (HR 2.07; 95% CI: 1.2-3.3; P = 0.002), and metastasis-free survival (HR 2.45; 95% CI: 1.37-4.4; P = 0.003). CONCLUSIONS: Cellular hyaluronan was significantly associated with unfavourable features and a poor prognosis in RCC. Further studies are needed to investigate the biological mechanism underlying hyaluronan accumulation in RCC.

Incidence of subsequent primary cancers and radiation-induced subsequent primary cancers after low dose-rate brachytherapy monotherapy for prostate cancer in long-term follow-up.

BACKGROUND: As aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs). METHODS: During the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated. RESULTS: During the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively. CONCLUSION: The crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.

Symptoms and diagnostic delays in bladder cancer with high risk of recurrence: results from a prospective FinnBladder 9 trial.

PURPOSE: To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC). METHODS: This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed. RESULTS: At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03). CONCLUSIONS: Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.

Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension.

BACKGROUND: It remains unclear whether patients with positive surgical margins or extracapsular extension benefit from adjuvant radiotherapy following radical prostatectomy. OBJECTIVE: To compare the effectiveness and tolerability of adjuvant radiotherapy following radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: This was a randomised, open-label, parallel-group trial. A total of 250 patients were enrolled between April 2004 and October 2012 in eight Finnish hospitals, with pT2 with positive margins or pT3a, pN0, M0 cancer without seminal vesicle invasion. INTERVENTION: A total of 126 patients received adjuvant radiotherapy at 66.6Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical recurrence-free survival, which we analysed using the Kaplan-Meier method and Cox proportional hazard regression. Overall survival, cancer-specific survival, local recurrence, and adverse events were secondary endpoints. RESULTS AND LIMITATIONS: The median follow-up time for patients who were alive when the follow-up ended was 9.3yr in the adjuvant group and 8.6yr in the observation group. The 10-yr survival for biochemical recurrence was 82% in the adjuvant group and 61% in the observation group (hazard ratio [HR] 0.26 [95% confidence interval {CI} 0.14-0.48], p<0.001), and for overall survival 92% and 87%, respectively (HR 0.69 [95% CI 0.29-1.60], p=0.4). Two and four metastatic cancers occurred, respectively. Out of the 43 patients with biochemical recurrence in the observation group, 37 patients received salvage radiotherapy. In the adjuvant group, 56% experienced grade 3 adverse events, versus 40% in the observation group (p=0.016). Only one grade 4 adverse event occurred (adjuvant group). A limitation of this study was the number of patients. CONCLUSIONS: Adjuvant radiotherapy following radical prostatectomy is generally well tolerated and prolongs biochemical recurrence-free survival compared with radical prostatectomy alone in patients with positive margins or extracapsular extension. PATIENT SUMMARY: Radiotherapy given immediately after prostate cancer surgery prolongs prostate-specific antigen progression-free survival, but causes more adverse events, when compared with surgery alone.

Long-term efficacy and urological toxicity of low-dose-rate brachytherapy (LDR-BT) as monotherapy in localized prostate cancer.

PURPOSE: The purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa). METHODS AND MATERIALS: During the years 1999-2008, 241 patients with PCa who underwent LDR-BT with I125 and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed. RESULTS: All D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores (p = 0.016) and higher initial urine residual volumes (p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively. CONCLUSIONS: The treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.

Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography.

OBJECTIVES: To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU). METHODS: During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test. RESULTS: Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T-MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv. CONCLUSIONS: Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02606513.

Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non-Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study.

BACKGROUND: Patients with non-muscle-invasive bladder cancer (NMIBC) belonging to the intermediate-risk group should be treated with intravesical instillations to prevent recurrence and progression. OBJECTIVE: We compared the outcome of a monthly maintenance bacillus Calmette-Guérin (BCG) regimen with that of epirubicin (EPI) and interferon-α2a (IFN) in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Our prospective randomized multicenter study comprised 229 eligible patients with frequently recurrent TaT1 grade 1-2 or low-grade NMIBC enrolled between 1997 and 2008. INTERVENTIONS: The four-arm study involved a single perioperative instillation of EPI plus five weekly instillations of BCG or EPI/IFN, followed by 11 monthly instillations in the 1-yr BCG or EPI/IFN maintenance arms, further followed by four additional quarterly instillations in the two 2-yr maintenance arms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence, progression, disease-specific survival, and overall mortality were analyzed using the Kaplan-Meier and cumulative incidence analyses plus the Cox and proportional subdistribution hazards models. RESULTS AND LIMITATIONS: The median follow-up time was 7.5 and 7.4 yr in the BCG and EPI/IFN groups, respectively. The probability of recurrence was significantly lower in the BCG group than in the EPI/IFN group. The probability was 39% versus 72% at 7.4 yr, respectively (hazard ratio [HR]: 0.41; 95% confidence interval [CI], 0.28-0.60; p<0.001). There was no significant difference in the probability of progression or in overall survival. However, there was a significant difference in disease-specific mortality in favor of the BCG group (HR: 0.20; 95% CI, 0.04-0.91; p=0.04). CONCLUSIONS: The monthly maintenance BCG regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of EPI/IFN-α2a. PATIENT SUMMARY: A monthly bacillus Calmette-Guérin (BCG) regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of epirubicin and interferon-α2a. TRIAL REGISTRATION: Registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1997, before the current requirements concerning study registrations were implemented.

Long-term outcome of patients with frequently recurrent non-muscle-invasive bladder carcinoma treated with one perioperative plus four weekly instillations of mitomycin C followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon-α2b instillations: prospective randomised FinnBladder-4 study.

BACKGROUND: Recurrent TaT1 non-muscle-invasive bladder cancer (NMIBC) patients should be treated with immediate instillation of chemotherapy after transurethral resection of bladder tumour followed by instillation therapy. OBJECTIVE: To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1-2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study. INTERVENTION: One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses. RESULTS AND LIMITATIONS: The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98-4.13; p<0.001). There were no significant differences in the probability of progression, disease-free mortality, or overall survival. CONCLUSIONS: Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence. PATIENT SUMMARY: We demonstrated in non-muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78-80% to 43-45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guérin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b. TRIAL REGISTRATION: The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.

TWIST overexpression predicts biochemical recurrence-free survival in prostate cancer patients treated with radical prostatectomy.

OBJECTIVE: The aim of this study was to determine whether TWIST and androgen receptor (AR) expression can predict the outcome in radical prostatectomy (RP) patients. MATERIAL AND METHODS: Samples from different tumour areas of 181 prostate cancer patients were analysed for TWIST and AR expression, and the results were correlated with known clinicopathological data and biochemical recurrence-free survival (BFS). RESULTS: TWIST overexpression in the margin area of the tumour (M-TWIST) was related to positive surgical margin (p = 0.047), capsule invasion (p = 0.006) and biochemical recurrence (BCR) (p = 0.004). AR expression in the margin area of the tumour (M-AR) was associated with high Gleason score (p = 0.004), positive surgical margin (p = 0.004) and BCR (p = 0.05). M-TWIST overexpression was clearly associated with M-AR expression (p < 0.0001). Four parameters, i.e. M-TWIST overexpression (p < 0.0001), positive surgical margin (p = 0.003), high Gleason score (p < 0.0001) and M-AR expression (p = 0.008), predicted BFS. In the multivariate analysis, M-TWIST overexpression (p = 0.011) and Gleason score (p = 0.002) were the only independent predictors of BFS. CONCLUSIONS: M-TWIST overexpression is associated with clinicopathological prognosis factors and M-AR overexpression and is a powerful independent predictor of BFS in conjunction with the Gleason score in prostate cancer patients treated with RP.

Increased nuclear factor erythroid 2-related factor 2 expression predicts worse prognosis of prostate cancer patients treated with radical prostatectomy.

Reactive oxygen species are known to be linked with cell damage leading to carcinogenesis. Augmented levels of oxidative stress biomarkers, such as nuclear factor erythroid 2-related factor 2 (Nrf-2) and 8-hydroxydeoxyguanosine (8-OHDG), have been shown to associate with more aggressive behavior in many malignancies. The aim of this study was to determine whether Nrf-2 and 8-OHDG expression could predict the outcome in radical prostatectomy patients. Samples of 240 prostate cancer patients were analyzed for Nrf-2 and 8-OHDG expression by immunohistochemistry. The results were compared with clinicopathological data, biochemical recurrence-free survival (BFS), prostate cancer-specific survival, and overall survival (OS). Positive expression of 8-OHDG (P < .0001), Nrf-2 in cytoplasm (c-Nrf-2) (P = .015), and Nrf-2 in nucleus (n-Nrf-2) (P = .016) was more abundant in malignant tissue compared with benign, respectively. Elevated level of c-Nrf-2 expression was associated with positive surgical marginal (P = .005), extraprostatic extension (P = .031), biochemical recurrence (BCR) (P = .030), and OS (P = .002); and n-Nrf-2 expression was associated with pathologic stage class (P = .001), Gleason score (P = .026), extraprostatic extension (P = .027), BCR (P = .037), and OS (P < .0001). The increased c-Nrf-2 expression predicted shortened BFS (P = .034) and worse OS (P = .017). In the multivariate analysis, c-Nrf-2 (P = .028 and P = .019) and Gleason score (P = .001 and P = .033) were independent predictors of BFS and OS, respectively. Expression of the analyzed biomarkers was not linked with prostate cancer-specific survival. Expression of 8-OHDG was not associated with any clinicopathological factors or survival. These results reveal that increased c-Nrf-2 expression is a predictor of BFS and OS in conjunction with Gleason score in prostate cancer patients treated with radical prostatectomy.

Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.

UNLABELLED: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems. OBJECTIVE: • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control. METHODS: • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50 mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index. RESULTS: • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P = 0.02). • The number of patients with an IPSS change of ≥ 3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P = 0.02). • Both treatments were safe and well tolerated. CONCLUSIONS: • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.

Absorption of different oral dosage forms of oxycodone in the elderly: a cross-over clinical trial in patients undergoing cystoscopy.

PURPOSE: To characterize the pharmacokinetics (PK) of oxycodone following intravenous injection and administration of three oral dosage forms (solution, capsule, and controlled-release tablet) in elderly patients (age 76-89 years) undergoing cystoscopy. METHODS: This was an open, randomized study with two sequences and two visits in 15 elderly patients. The patients were given intravenous injection (over 10 min) of 5 mg of oxycodone hydrochloride trihydrate. Oxycodone hydrochloride (5 mg in all forms) was orally administered as a solution, a capsule, and a controlled-release tablet. Venous blood samples were collected up to 17 h after oxycodone administration. Population PK parameters were calculated with NONMEM VI 2.0. For intravenous injection we calculated clearance, volume of distribution at steady state, and the half-life of elimination, and for oral dosage forms also the absolute bioavailability. RESULTS: Clearance of the intravenous injections was 28.9 L/h; the volume of distribution at steady state and the half-life of elimination were 186 L and 5.2 h, respectively. The absolute bioavailability of oxycodone was 59 % from oral solutions, 64 % from capsules, and 55 % from controlled-release tablets. CONCLUSIONS: Our results indicate that, in the elderly, the bioavailability of the three different oral dosage forms of oxycodone is fairly similar.

Does the outcome of prostate cancer patients with large prostates differ from small prostate size in permanent seed, low dose-rate brachytherapy?

OBJECTIVE: Brachytherapy has good results in the treatment of early prostate cancer (PC). The procedure is challenging in large prostates, and the optimal prostate volume for brachytherapy was previously defined as ≤40 ml. This study analysed the outcome of PC patients with small (group A) and large (group B) prostate volume in prospective data. MATERIAL AND METHODS: The material consisted of 535 consecutive patients treated with brachytherapy in Kuopio University Hospital. The mean follow-up time was nearly 6 years. Prostate-specific antigen (PSA) failure was defined as PSA rising ≥2.0 µg/l above nadir. A PSA bounce was defined as a rise in PSA of ≥0.2 µg/l. The causes of death were recorded. RESULTS: A bounce was recorded more frequently in group A (30%) than in group B (18%) (p = 0.006). A bounce correlated with young age predicted a favourable outcome in both groups. PSA failure rate was similar in both groups: 13% and 12% in groups A and B, respectively. Post-treatment PSA ≤0.5 µg/l was the only independent prognostic factor associated with PSA failure in both groups (p < 0.0001, both groups). PC survival was 98.4% in both groups. Overall survival was 91% and 94% in groups A and B, respectively (p = not significant). CONCLUSIONS: There were no differences between the PC patients with small and large prostate volumes treated with brachytherapy with respect to PSA failure rate, PC survival or overall survival. All patients, independent of prostate size, are potential candidates for brachytherapy.

A short biodegradable helical spiral ureteric stent provides better antireflux and drainage properties than a double-J stent.

OBJECTIVE: The use of ureteric stents is a standard treatment for the relief of ureter blockages for benign or malignant reasons. The most common stent design in clinical use is a double-J stent with coiled ends to avoid stent displacement. However, there are a number of complications associated with stent use. A double-J stent design bypasses the ureterovesical junction, enables bladder pressure reflection to the renal pelvis and causes vesicoureteral reflux (VUR). This may result in scarring and renal failure. MATERIAL AND METHODS: An animal model was used to investigate whether VUR can be avoided in stented ureters using a short biodegradable partial helical spiral stent design that leaves the ureterovesical junction intact. MATERIALS AND METHODS: Eight female pigs were used. Ureters on the left side were stented using a short helical spiral SR-PLGA stent (group A) and ureters on the right side using double-J stents (group B). Simulated voiding cystoureterography and standard intravenous urography examinations were performed on all eight animals at 4 weeks and on the remaining four animals at 8 weeks. RESULTS: An SR-PLGA single coiled partial stent demonstrated superior drainage properties to a double-J stent at 4 weeks (p = 0.020). A marked but not statistically significant difference in favour of a SR-PLGA stent was also observed at 8 weeks (p = 0.102). A statistically significant difference was observed in VCUG findings in favour of group A at immediate postoperative control as well as in the 4 and 8 week follow-up studies (p = 0.011, p = 0.010, p = 0.046, respectively). CONCLUSION: A self-expandable, SR-PLGA partial ureteric stent presented with superior drainage and antireflux properties compared to a double-J stent. The reflux commonly related to double-J stent use can be minimized by using a partial ureteric stent design.