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- Comparative Effectiveness of Robot-assisted Versus Open Radical Prostatectomy Cancer Control. [JOURNAL ARTICLE]
- Eur Urol 2014 Feb 19.
Robot-assisted radical prostatectomy (RARP) remains controversial, and no improvement in cancer control outcomes has been demonstrated over open radical prostatectomy (ORP).To examine population-based, comparative effectiveness of RARP versus ORP pertaining surgical margin status and use of additional cancer therapy.This was a retrospective observational study of 5556 RARP and 7878 ORP cases from 2004 to 2009 from Surveillance Epidemiology and End Results-Medicare linked data.RARP versus ORP.Propensity-based analyses were performed to minimize treatment selection biases. Generalized linear regression models were computed for comparison of RP surgical margin status and use of additional cancer therapy (radiation therapy [RT] or androgen deprivation therapy [ADT]) by surgical approach.In the propensity-adjusted analysis, RARP was associated with fewer positive surgical margins (13.6% vs 18.3%; odds ratio [OR]: 0.70; 95% confidence interval [CI], 0.66-0.75), largely because of fewer RARP positive margins for intermediate-risk (15.0% vs 21.0%; OR: 0.66; 95% CI, 0.59-0.75) and high-risk (15.1% vs 20.6%; OR: 0.70; 95% CI, 0.63-0.77) disease. In addition, RARP was associated with less use of additional cancer therapy within 6 mo (4.5% vs 6.2%; OR: 0.75; 95% CI, 0.69-0.81), 12 mo (OR: 0.73; 95% CI, 0.62-0.86), and 24 mo (OR: 0.67; 95% CI, 0.57-0.78) of surgery. Limitations include the retrospective nature of the study and the absence of prostate-specific antigen levels to determine biochemical recurrence.RARP is associated with improved surgical margin status relative to ORP for intermediate- and high-risk disease and less use of postprostatectomy ADT and RT. This has important implications for quality of life, health care delivery, and costs.Robot-assisted radical prostatectomy (RP) versus open RP is associated with fewer positive margins and better early cancer control because of less use of additional androgen deprivation and radiation therapy within 2 yr of surgery.
- Greatest Percentage of Involved Core Length and the Risk of Death From Prostate Cancer in Men With Highest Gleason Score ≥ 7. [JOURNAL ARTICLE]
- Clin Genitourin Cancer 2014 Feb 4.
Men with highest GS ≥ 7 and a differing, lower GS core (ComboGS) have decreased PC-specific mortality (PCSM) risk after RT or RT and androgen deprivation therapy (ADT). Whether the greatest percentage of involved core length (GPC) modulates this risk is unknown.Men with GS ≥ 7 PC (n = 333) consecutively treated between December 1989 and July 2000 using RT (n = 268; 80%) or RT and 6 months of ADT (n = 65; 20%) comprised the study cohort. The GPC was calculated using biopsy core and tumor lengths. We used competing risks regression to assess whether increasing GPC was associated with increased PCSM risk in men with or without ComboGS adjusting for risk group, age, and treatment.After a median follow-up of 5.36 years (interquartile range, 3.22-7.61 years), 92 (28%) men died, 28 (30%) of PC. Increasing GPC was significantly associated with increased risk of PCSM (adjusted hazard ratio, 1.02; 95% confidence interval, 1.01-1.03; P = .005). Men with GPC ≥ 50% versus < 50% had significantly greater PCSM estimates when ComboGS was present (P < .001) versus absent (P = .55). Of the 127 men with ComboGS and GPC < 50%, 83% were treated with RT alone and 2 PC deaths were observed; neither in men with GS 7 and favorable intermediate-risk PC.Men treated with RT for ComboGS, GPC < 50%, GS 7, and favorable intermediate-risk PC have a very low risk of early PCSM. The RTOG 0815 trial will establish whether ADT is necessary to optimize curability in these men.
- Current trends for the use of androgen deprivation therapy in conjunction with radiotherapy for patients with unfavorable intermediate-risk, high-risk, localized, and locally advanced prostate cancer. [JOURNAL ARTICLE]
- Cancer 2014 Mar 3.
Androgen deprivation therapy (ADT) is now a well-established standard of care in combination with definitive radiotherapy for patients with unfavorable intermediate-risk to high-risk locally advanced prostate cancer. It is also well established that combination modality treatment with ADT and radiotherapy is superior to either of these modalities alone for the treatment of patients with high-risk locally advanced disease. Current treatment guidelines for prostate cancer in the United States are based on the estimated risk of recurrence and death. This review examines the clinical evidence underpinning the use of ADT and radiotherapy among patients with high-risk localized and locally advanced disease in the United States. This review also considers the rationale for moving from traditional luteinizing hormone-releasing hormone agonists to more recently developed gonadotrophin-releasing hormone antagonists. Cancer 2014. © 2014 American Cancer Society.
- Up-to-date results of carbon-ion radiotherapy for prostate cancer. [Journal Article]
- J Radiat Res 2014 Mar 1.:i28-i29.
Carbon ion radiotherapy (C-ion RT) for prostate cancer was started in 1995 using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS), Japan. After preceding phase I/II dose-escalation studies of 20 fractions over 5 weeks, a phase II study was initiated in April 2000 using the treatment techniques and the recommended dose fractionations established by the phase I/II studies. This study was also successfully completed in October 2003 when the C-ion RT for solid tumors, including the prostate cancer, was approved as 'Advanced Medicine' by the Ministry of Health, Labor, and Welfare. Since then, more than 1400 patients have been treated with C-ion RT as of February 2012, and advancement of hypofractionation has also been achieved. In this paper, the treatment outcomes in 1144 patients who underwent the established C-ion RT between April 2000 and July 2012 were analyzed. Out of 1144 patients, 585 patients were categorized as high-risk group, which includes patients having at least one of the following conditions: T3 clinical stage, Gleason's score of 8 or higher and PSA of 20 or higher. One hundred and ninety-seven patients who met the conditions such as clinical stage of T2a or lower, Gleason's score of 6 or lower and PSA of <20 were categorized as low-risk group. Three hundred and sixty-two patients who were not included in either high- or low-risk group were categorized as intermediate-risk group. All patients were pathologically proven to have adenocarcinoma of the prostate, and Gleason's score was determined by the chief pathologist of our study group. Written consent was obtained from all patients included in the clinical study. Patients with the following conditions were not registered in the clinical trial: having distant metastases, having synchronous primary malignancy, not histologically proven cancer, without informed consent, post-operative/post-irradiation recurrence. All patients were treated with three field irradiations (vertical one field and horizontal opposing two fields). The prostate and proximal part of the seminal vesicle were contoured as clinical target volume (CTV), and planning target volume (PTV) was set with 5-10 mm margins around the CTV. On the way of radiotherapy, a part of irradiation field of the posterior side was cut to reduce the rectal dose. The 197 patients in the low-risk group did not undergo androgen deprivation therapy (ADT), whereas the 947 patients of intermediate- and high-risk groups underwent ADT. The patients of intermediate-risk group underwent about 6 months of neoadjuvant ADT, and the patients of high-risk group also underwent about 6 months of neoadjuvant ADT and sequential adjuvant ADT for more than 18 months. The median age of all patients was 68 years, and the median follow-up time was 48.7 months (range: 3.6-151.1 months). The 5-year overall survival rate and biochemical relapse-free rate of the entire groups was 95.7% and 91.0%, respectively. T-stage and Gleason's score were significant prognostic factors for both the biochemical control and patient survival and initial PSA was also a predictive factor for survival. Regarding the late radiation toxicity, the incidence of rectal toxicity of grade 2 or worse was 1.1% and that of genitourinary toxicity was 6.5%. These outcomes seemed to be better than those of the past publications [ 1- 4]. In addition, the incidence of toxicity in patients treated with more hypofractionated C-ion RT of 16 fractions over 4 weeks was lower than those of 20 fraction treatment. These favorable outcomes can be thought as apparent evidence of physical and biological advantages of the hypofractionated C-ion RT.
- A Cross-Sectional Study of the Plantar Flexor Muscle and Tendon during Growth. [JOURNAL ARTICLE]
- Int J Sports Med 2014 Feb 27.
The purpose of this study was to investigate growth changes in human plantar flexor muscle and tendons. In addition, we ascertained whether growth changes in muscle and tendon were more closely related to skeletal age than chronological age. 22 elementary school children (ESC), 19 junior high school students (JHS), and 23 young adults (ADT) men participated in this study. Maximal strain and hysteresis of tendon structures and cross-sectional area of Achilles tendon were measured using ultrasonography. In addition, skeletal age was assessed using Tanner-Whitehouse III method. Maximal strain of ESC was significantly greater than that of other groups, while no significant difference was observed between JHS and ADT. There was no difference in hysteresis among 3 groups. Relative cross-sectional area (to body mass2/3) of ADT was significantly smaller than that of other groups. For ESC and JHS, measured variables of muscle and tendon were significantly correlated to both chronological and skeletal ages. These results suggested that immature musculoskeletal system was protected by more extensible and larger tendon structures in ESC and only by larger tendon structures in JHS, respectively. Furthermore, there were no differences in correlation coefficient values between measured variables of muscle and tendon and chronological or skeletal ages.
- Androgen receptor promotes the oncogenic function of overexpressed Jagged1 in prostate cancer by enhancing cyclin B1 expression via Akt phosphorylation. [JOURNAL ARTICLE]
- Mol Cancer Res 2014 Feb 26.
The Jagged1, a Notch signaling pathway ligand, had been shown has a positive correlation with the prostate cancer development. Our study for the Jagged1 expressions in 218 prostate cancer tissue samples also supports this conclusion. But the detailed molecular mechanism of the Jagged1 in promoting the prostate cancer progression is still unclear. Through the cell proliferation examination, androgen receptor (AR) was found can promote the oncogenic function of the Jagged1 to enhance the cell proliferation rate by comparing four prostate cancer cell lines, LNCaP, LAPC4, DU145 and PC3, which was further validated through analyzing survival of 118 patients treated with androgen deprivation therapy (ADT) with different expression levels of the Jagged1 and AR. More importantly, our data showed that the Jagged1 combined with AR can increase the phosphorylation level of Akt and, in return, the phosphorylated Akt plays an important role in regulating the expression level of cyclin B1 by interacting with AR and increasing the transcriptional activity of AR. These data indicate that the prostate cancer progression regulated by the Jagged1 can be dramatically enhanced by combining with AR through promoting the activity of Akt. Implications: This study could benefit our clinical treatments for the prostate cancer patients with overexpressed Jagged1 by targeting AR and Akt.
- Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy? [JOURNAL ARTICLE]
- Eur J Nucl Med Mol Imaging 2014 Feb 25.
To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse.We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT.Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT.Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.
- The Use of Androgen Deprivation Therapy (ADT) and Chemotherapeutic Agents in New Zealand Men with Prostate Cancer. [Journal Article]
- J Cancer 2014; 5(3):214-20.
Purpose:To assess the patterns of use of androgen deprivation therapy (ADT) and chemotherapeutic agents in New Zealand men with prostate cancer.
Methods:Men diagnosed with prostate cancer between 2006 and 2011 were identified from the New Zealand Cancer Registry. Through data linkage with the Pharmaceutical Collection and the National Minimum Dataset information on subsidised anti-androgens, luteinising hormone-releasing hormone (LHRH) analogues, chemotherapeutic agents, and orchidectomy was retrieved. The frequency of ADT and chemotherapy use in the first year post-diagnosis was assessed by patients' age, ethnicity, and extent of disease at diagnosis.
Results:The study population included 15,947 men diagnosed with prostate cancer, of whom 4978 (31%) were prescribed ADT or chemotherapeutic agents. ADT was dispensed for 72% of men with metastatic disease. Only 24 (0.2%) men received chemotherapeutic agents. Men with advanced (regional or metastatic) disease older than 70 were more likely to receive anti-androgens only and to be treated with orchidectomy compared with younger men. Māori and Pacific men (compared with non-Māori/non-Pacific men) were more likely to receive pharmacologic ADT, and Māori men were also more likely to be treated with orchidectomy.
Conclusions:It was expected that all men diagnosed with metastatic prostate cancer should be using ADT in the first year post-diagnosis. However, for more than one-fourth of men neither anti-androgens nor LHRH analogues were dispensed within this period. Chemotherapeutic agents were used very rarely, so it seems that both pharmacologic ADT and chemotherapy is under-utilised in New Zealand patients with advanced prostate cancer.
- Osteoporosis and prostate cancer: a cross-sectional study of Danish men with prostate cancer before androgen deprivation therapy. [JOURNAL ARTICLE]
- Scand J Urol 2014 Feb 19.
Abstract Objective. The aim of this study was to analyse the prevalence of osteoporosis and risk factors of osteoporotic fractures before androgen deprivation in Danish men. Treatment and prognosis of prostate cancer necessitate management of long-term consequences of androgen deprivation therapy (ADT), including accelerated bone loss resulting in osteoporosis. Osteoporotic fractures are associated with excess morbidity and mortality. Material and methods. Patients with prostate cancer awaiting initiation of ADT were consecutively included. Half of the patients had localized disease and were referred for curative intended radiation, and the remaining patients had disseminated disease. Blood samples were collected, a questionnaire was administered and a dual-energy X-ray absorptiometry (DXA) scan was performed before initiating ADT. The patients were included between January 2010 and March 2012. The study was approved by the local ethics committee. None of the patients had received prior androgen deprivation or osteoporosis treatment. Results. In total, 105 individuals were included. The mean age of the participants was 70 years (range 53-91 years, SD 6.3). The median prostate-specific antigen level was 30.5 g/l (1-5714 g/l). The average Gleason score was 7.8 (range 5-10, SD 1.1). Fifty patients had localized prostate cancer and the other 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% before ADT. There was no significant difference between the two subgroups concerning osteoporosis. Smoking use was the only factor that was significantly associated with an increased prevalence of osteoporosis in the study population. Conclusion. Two-thirds of patients with prostate cancer awaiting ADT had osteoporosis or reduced bone mass. Further awareness regarding osteoporosis and bone health in prostate cancer is needed. It is suggested that patients with prostate cancer undergo a DXA scan before starting ADT.
- Small cell carcinoma of the prostate. [JOURNAL ARTICLE]
- Nat Rev Urol 2014 Feb 18.
Pure small-cell carcinoma (SCC) of the prostate is a rare entity and one of the most aggressive malignancies of the prostate. Histologically, prostatic SCCs of the prostate are part of a spectrum of anaplastic tumours of the prostate and are similar to SCCs of the lungs. In most cases, SCC of the prostate is associated with conventional prostatic adenocarcinoma. Both components of these mixed tumours frequently share molecular alterations such as ERG gene rearrangements or AURKA and MYCN amplifications, suggesting a common clonal origin. The clinical behaviour of small-cell prostate carcinomas is characterized by extensive local disease, visceral disease, and low PSA levels despite large metastatic burden. Commonly, the emergence of the SCC occurs in patients with high-grade adenocarcinoma who are often treated with androgen deprivation treatment (ADT). However, SCCs do not usually benefit from ADT. A biopsy of accessible lesions is strongly recommended to identify those with SCC pathological features, as management is undoubtedly affected by this finding. Chemotherapy is the standard approach for treating patients with either localized or advanced prostatic SCC. Despite the emergence of more-aggressive treatment modalities, the prognosis of men with prostatic SCC remains dismal.