Albertas Ulys

Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

PURPOSE Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. PATIENTS AND METHODS In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory-Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. RESULTS The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). CONCLUSION Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity.

Does quality of life of prostate cancer patients differ by stage and treatment

Background: The lack of consensus amongst experts delineate how important it is for patients diagnosed with prostate cancer (PCa) to make an informed decision on available treatment options through an objective discussion of the risks and benefits. One of important benefits could be seen as patient’s quality of life (QoL) after treatment. We aimed to assess QoL differences in prostate cancer patients by stage and treatment for a population-based sample. Methods: The cross-sectional PCa patient population-based national level study for a prostate cancer patient population was performed. QoL was investigated with EORTC QLQ-C30. The analysis includes descriptive statistics and evaluation of differences in functional and symptom scales by stage and treatment group by predictors in the model. Results: Response rate was 79.1% (N=514). The highest QoL scores were observed in localised PCa, active surveillance treatment group. The lowest scores were observed in advanced stages, chemotherapy treatment group. Between cancer stages, statistically significant differences were observed only in scales of emotional functioning (p<0.001) and social functioning (p<0.001). Between treatment groups, statistically significant differences were observed in scales of physical functioning (p<0.001), role functioning (p<0.001), emotional functioning (p<0.001), and social functioning (p<0.001). Conclusions: Our study highlighted statistically significant differences in QoL between cancer stages and treatment. Understanding how the QoL changes in relation with the selected treatment option can be important to the urologist and individual patient to have realistic expectations as well as to optimise treatment decisions for the prostate cancer patient when exist several alternatives.

Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer.

BACKGROUND The aim of the study was to assess the expression of the MMP-9 gene and -1562 C/T polymorphism in MMP-9 gene promoter in relation to clinicopathological parameters in predicting the clinical outcome of prostate cancer patients. METHODS A total of 82 patients with histopathologically diagnosed prostate cancer were enrolled in the study. MMP-9 gene expression was assessed by reverse transcription-PCR method. MMP-9 (-1562 C/T) polymorphism variants were determined by the polymerase chain reaction-based restriction fragment length polymorphism method. RESULTS MMP-9 expression and MMP-9 -1562 polymorphism variants in relation to disease pathological stage (P = 0.006; P <0.0001, respectively), as well as to prognostic group (P = 0.019; P <0.0001, respectively), were statistically significant. Only MMP-9 -1562 polymorphism variants in relation to tumor differentiation grade (P = 0.044) were found to be statistically significant. Positive MMP-9 gene expression was associated with 5-year survival rate of prostate cancer patients with pathological stage III (P = 0.036) and for the patients in prognostic group III (P = 0.012). Patients with tumor differentiation grade G2 and with the identified CC variant had a significantly longer survival time than patients with the identified TT variant (P = 0.007). CONCLUSIONS MMP-9 gene expression and MMP-9 -1562 polymorphism variants were associated with prostate cancer pathological stage and prognostic group. MMP-9 -1562 polymorphism CC variant was associated with prostate cancer tumor differentiation grade. Five-year survival analysis showed the relationship between MMP-9 gene expression and pathological stage III, as well as prognostic group III, whereas MMP-9 -1562 polymorphism variants, with tumor differentiation grade G2.

Cancer surveillance using registry data: Results and recommendations for the Lithuanian national prostate cancer early detection programme.

INTRODUCTION We describe long term trends in prostate cancer epidemiology in Lithuania, where a national prostate specific antigen (PSA) test based early detection programme has been running since 2006. METHODS We used population-based cancer registry data, supplemented by information on PSA testing, life expectancy and mortality from Lithuania to examine age-specific prostate cancer incidence, mortality and survival trends among men aged 40+ between 1978 and 2009, as well as life expectancy of screening-eligible men, and the proportion of men with a first PSA test per year since the programme started. RESULTS The number of prostate cancer patients rose from 2.237 in 1990-1994 to 15.294 in 2005-2009. By 2010, around 70% of the eligible population was tested, on average around two times. The early detection programme brought about the highest prostate cancer incidence peaks ever seen in a country to date. Recent incidence and survival rises in the age groups 75-84 suggest PSA testing in the elderly non-eligible population. Life expectancy of men aged 70-74 indicates that less than 30% of patients will live for 15 years and may have a chance to benefit from early detection. CONCLUSIONS Early detection among men aged 70-74, and particularly among the elderly (75+) may have to be reconsidered. Life expectancy assessment before testing, avoiding a second test among men with low PSA values and increasing the threshold for further evaluation and the screening interval may help reducing harm. Publishing information on treatment modalities, side-effects and patient reported quality of life is recommended.

Clinical significance of miRNA host gene promoter methylation in prostate cancer

Abstract Only a part of prostate cancer (PCa) patients has aggressive malignancy requiring adjuvant treatment after radical prostatectomy (RP). Biomarkers capable to predict biochemical PCa recurrence (BCR) after RP would significantly improve preoperative risk stratification and treatment decisions. MicroRNA (miRNA) deregulation has recently emerged as an important phenomenon in tumor development and progression, however, the mechanisms remain largely unstudied. In the present study, based on microarray profiling of DNA methylation in 9 pairs of PCa and noncancerous prostate tissues (NPT), host genes of miR‐155‐5p, miR‐152‐3p, miR‐137, miR‐31‐5p, and miR‐642a, ‐b were analyzed for promoter methylation in 129 PCa, 35 NPT, and 17 benign prostatic hyperplasia samples (BPH) and compared to the expression of mature miRNAs and their selected targets (DNMT1, KDM1A, and KDM5B). The Cancer Genome Atlas dataset was utilized for validation. Methylation of mir‐155, mir‐152, and mir‐137 host genes was PCa‐specific, and downregulation of miR‐155‐5p significantly correlated with promoter methylation. Higher KDM5B expression was observed in samples with methylated mir‐155 or mir‐137 promoters, whereas upregulation of KDM1A and DNMT1 was associated with mir‐155 and mir‐152 methylation status, respectively. Promoter methylation of mir‐155, mir‐152, and mir‐31 was predictive of BCR‐free survival in various Cox models and increased the prognostic value of clinicopathologic factors. In conclusion, methylated mir‐155, mir‐152, mir‐137, and mir‐31 host genes are promising diagnostic and/or prognostic biomarkers of PCa. Methylation status of particular miRNA host genes as independent variables or in combinations might assist physicians in identifying poor prognosis PCa patients preoperatively.

Factors affecting health-related quality of life in prostate cancer patients

Abstract Objective. Prostate cancer is the most common cancer among men in Lithuania. Quality of life (QoL) assessment plays a key role in the evaluation and treatment of cancer patients. The aim of this study was to evaluate factors affecting the QoL of patients with prostate cancer in Lithuania. Material and methods. A cross-sectional national-level study was performed. QoL was investigated with the EORTC QLQ-C30 questionnaire. Statistical analysis included descriptive statistics, interrelationship analysis between characteristics and multivariate logistic regression to estimate predictors and odds ratios (ORs) for each of the independent variables in the model. Results. The response rate was 74.8% (N = 486). One-quarter of respondents with prostate cancer indicated high QoL scores. Higher QoL scores were given for prostate cancer patients with lower education level [OR = 3.092, 95% confidence interval (CI) 1.007–9.491, p = 0.049], having lower monthly expenses for treatment (OR = 3.653, CI 1.318–10.128, p = 0.013), disease stage II (by patient conveyance) (OR = 10.053, CI 1.015–99.534, p = 0.048), disease stage I (by medical record) (OR = 2.19E + 08, CI 218514200.17–218514200.17, p < 0.001) and in those with undisclosed disease stage (OR = 9.220, CI 1.251–67.965, p = 0.029). Conclusions. Significant predictors for higher QoL scores were education level, own monthly expenses for treatment and disease stage. Patients with undisclosed disease stage more often had higher QoL scores.

Extralobar pulmonary sequestration

Prevalence of pulmonary sequestration accounts for up to 6.4% of all congenital pulmonary malformations. We report on a 40-year-old woman who underwent excision of an aberrant solid retroperitoneal mass in the left subdiaphragmatic area. The mass was identified to be an extralobar pulmonary sequestration. The diagnosis could be made without surgery by percutaneous tissue biopsy and imaging. We encourage keeping in mind pulmonary sequestration anomaly presenting as an aberrant retroperitoneal mass. The aim of this case report is to increase awareness about the condition and review the criteria for its definitive diagnosis and treatment.

Gracilis muscle interposition with primary rectal without urethral repair for moderate sized rectourethral fistula caused by brachytherapy for prostate cancer: a case report

IntroductionThere is a 0.16% chance of a rectourethral fistula after prostate brachytherapy monotherapy using Palladium-103 or Iodine-125 implants. We present an unusual case report of a rectourethral fistula following brachyradiotherapy monotherapy for prostate adenocarcinoma. It was also associated with unusual management of the fistula.Case presentationA 58-year-old Caucasian man underwent brachyradiotherapy monotherapy as definitive treatment for verified intracapsular prostate adenocarcinoma receiving 56 Iodine-125 implants using a transrectal ultrasound-guided technique. The patient started to complain of severe perineal pain and mild rectal bleeding 15Â months after brachyradiotherapy. A biopsy of mucosa of his anterior rectal wall was performed. A moderate sized rectourethral fistula was confirmed 23Â months after implantation of Iodine-125 seeds. Laparoscopic sigmoidostomy and suprapubic cystostomy were then performed. Long-term cortisone applications in combination with 30 sessions of hyperbaric oxygen therapy, and antibacterial therapies were initiated due to necrotic infection. A gracilis muscle interposition to create a partition between the patients rectum and urethra in conjunction with primary rectal repair but without urethral repair were performed 6 months later. The 3cm rectal defect was repaired via a 3cm-long horizontal perineal incision. The 1.5cm urethral defect just below the prostate was not repaired. The patient underwent an optic internal urethrotomy 3Â months later for a 1.5cm-long urethral stricture. Several planned preventive urethral buginages were performed to avoid urethral stricture recurrence. At 12Â months postoperatively, there were no signs of a fistula and cancer recurrence. He now has a normal voiding and anal continence.ConclusionSevere rectal pain, bleeding, and local anterior necrotic proctitis are predictors of a rectourethral fistula. Urinary and fecal diversion is the first-step operation. Gracilis muscle interposition in conjunction with primary rectal repair but without urethral reconstruction is one of the reconstructive surgery options for moderate 2cm to 3cm rectourethral fistulas. Internal urethrotomy is a procedure for postoperative urethral strictures of 1.5cm in length.

ABO blood group polymorphism has an impact on prostate, kidney and bladder cancer in association with longevity

The aim of the present study was to assess the ABO blood group polymorphism association with prostate, bladder and kidney cancer, and longevity. The following data groups were analyzed: Prostate cancer (n=2,200), bladder cancer (n=1,530), renal cell cancer (n=2,650), oldest-old (n=166) and blood donors (n=994) groups. The data on the ABO blood type frequency and odds ratio in prostate cancer patients revealed a significantly higher blood group B frequency (P<0.05); the pooled men and women, separate men bladder cancer risk was significantly associated with the blood group B (P<0.04); however, no such association was identified in the female patients. The blood group O was observed to have a significantly decreased risk of bladder cancer for females (P<0.05). No significance for the ABO blood group type in the studied kidney cancer patients was identified. A comparison of the oldest-old and blood donor groups revealed that blood group A was significantly more frequent and blood type B was significantly rarer in the oldest-olds (P<0.05). The results of the present study indicated that blood type B was associated with the risk of prostate and bladder cancer, and could be evaluated as a determinant in the negative assocation with longevity. Blood types O and A may be positive factors for increasing the oldest-old age likelihood. The clustering analysis by the ABO type frequency demonstrated that the oldest-olds comprised a separate cluster of the studied groups.

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy

Background This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. Results A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. ClinicalTrials gov identifier NCT01732549.BACKGROUND This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS Patients were randomly assigned (1:1) to receive tasquinimod (0.25-1.0mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7weeks (range 0.6-102.7weeks) for the tasquinimod arm and 19.2weeks (range 0.4-80.0weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9)weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P=0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.