Risk Of Prostate Cancer Recurrence Research Articles

The haemoglobin levels of patients with prostate cancer treated with radical radiotherapy

Introduction: The worldwide estimate points to prostate cancer as the second most frequent cancer in men worldwide, where radiotherapy has been an important modality of curative treatment in managing this neoplasia. The prevalence and impact of cancer-related anemia are not widely known, and it may be overlooked or considered clinically significant. It is believed that the outcomes and toxicity of radiotherapy in prostate cancer treatment may be influenced by blood hemoglobin levels. Objective: To evaluate hemoglobin levels in patients with prostate cancer before and after radiotherapy treatment. Methods: Retrospective, longitudinal study of patients diagnosed with malignant prostate neoplasms undergoing external radiotherapy. Hemoglobin levels were measured before radiotherapy and after treatment completion (20-40 days). Anemia was defined by the World Health Organization as men with values less than 13 g/dl. Prostate cancer recurrence risk classification was based on the National Comprehensive Cancer Network risk criteria. Results: Forty patients were evaluated with measurement of Hemoglobin levels before and after radiotherapy treatment. The mean age was 67 years. According to the risk group classification, 4 patients were low-risk (10%), 27 patients were intermediate-risk (67.5%), and 9 patients were high-risk (22.5%). The mean pre-radiotherapy Hemoglobin levels were 13.3 g/dL, and the mean post-radiotherapy Hemoglobin levels were 10.4 g/dL, p < 0.0001. Conclusion: In this study, a reduction in serum Hemoglobin levels was observed after radiotherapy, highlighting the need for better monitoring of these patients.

The Impact of Delayed Radical Prostatectomy on Recurrence Outcomes After Initial Active Surveillance: Results from a Large Institutional Cohort

Background and objectiveActive surveillance (AS) of prostate cancer (PCa) involves regular monitoring for disease progression. The aim is to avoid unnecessary treatment while ensuring appropriate and timely treatment for those whose disease progresses. AS has emerged as the standard of care for low-grade (Gleason grade 1, GG1) PCa. Opponents are concerned that initial undersampling and delay of definitive management for patients with GG2 disease may lead to adverse outcomes. We sought to determine whether the timing for definitive management of GG2 PCa, either upfront or after initial AS, affects recurrence outcomes after radical prostatectomy (RP). MethodsParticipants were diagnosed with cT1–2N0/xM0/x, prostate-specific antigen (PSA) <20 ng/ml, and GG1–2 PCa between 2000 and 2020 and underwent immediate RP for GG2 or AS followed by delayed RP on upgrading to GG2. The outcome was recurrence-free survival (RFS) after surgery, with recurrence defined as either biochemical failure (2 PSA measurements ≥0.2 ng/ml) or a second treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations between the timing for definitive RP and the risk of recurrence, adjusted for age at diagnosis, percentage of positive biopsy cores (PPC), PSA density, PSA before RP, year of diagnosis, surgical margins, genomic risk score, and prostate MRI findings.Key findings: Of the 1259 men who met the inclusion criteria, 979 underwent immediate RP after diagnosis of GG2, 190 underwent RP within 12 mo of upgrading to GG2 on AS, and 90 men underwent RP >12 mo after upgrading to GG2. The 5-yr RFS rates were 81% for the immediate RP group, 80% for the delayed RP ≤12 mo, and 70% for the delayed RP >12 mo group (univariate log-rank p = 0.03). Cox multivariable regression demonstrated no difference in RFS outcomes between immediate RP for GG2 disease and delayed RP after upgrading on AS. PPC (hazard ratio [HR] per 10% increment 1.08, 95% confidence interval [CI] 1.02–1.15; p = 0.01) and PSA before RP (HR 1.06, 95% CI 1.03–1.09; p < 0.01) were significantly associated with the risk of recurrence. Conclusionsand clinical implications: PPC and PSA before RP, but not the timing of definitive surgery after upgrade to GG2, were associated with the risk of PCa recurrence after RP on multivariable analysis. These findings support the safety of AS and delayed definitive therapy for a subset of patients with GG2 disease. Patient summaryIn a large group of 1259 patients with low-grade prostate cancer, we found that delaying surgical treatment after an initial period of active surveillance resulted in no differences in prostate cancer recurrence. Our results support the safety of active surveillance for low-grade prostate cancer.

Abstract A021: Prevalence of metabolic syndrome and its association with physical activity in African American prostate cancer survivors at baseline of Men Moving Forward, a lifestyle intervention program

Abstract Background: Black/African American (Bl/AA) men have the highest death rate from Prostate Cancer(PC) compared to any other race/ethnicity. PC is also the second leading cause of death in this population. Men Moving Forward (MMF) is the first community-based lifestyle intervention developed with and for African American Prostate Cancer Survivors (AAPCS). This study assesses the prevalence of Metabolic Syndrome(MetS) in MMF cohort at baseline and explores the association between physical activity (PA) and MetS. MetS is implicated as a possible risk factor for the progression of PC and is a well-established risk factor for Cardiovascular (CV) disease, the most common cause of death among PC survivors cured of their cancers. MetS is defined as having three or more risk factors: waist circumference &amp;gt; 40-inches, blood pressure (BP) &amp;gt; 130/80 mmHg, fasting blood glucose &amp;gt;100 mg/dl, HDL level &amp;lt;40mg/dl and triglyceride level &amp;gt; 150 mg/dl. Notably, physical inactivity is a known risk for MetS, CV disease and PC. Methods: MMF is a 16-week group-based lifestyle intervention, led by local health coaches. To be eligible, men must have a BMI &amp;gt; 23 kg/m2, completed treatment or on active surveillance, and non-adherent to ACS nutrition OR PA guidelines. Men complete surveys, physical assessments, and blood draws at baseline, post-intervention, and 12-months. Baseline waist circumference, resting BP measurement, fasting glucose level, HDL level, and triglyceride level were examined. PA was measured using the Godin Leisure-Time Exercise scale with scores stratified into three activity levels: insufficiently active (&amp;lt; 14 ), moderately active(14-23), and active(&amp;gt; 24). The association between PA and MetS was assessed using Chi-square test of independence. Results: 117 AAPCS were enrolled at baseline, with 98 having complete PA and MetS data. These participants had a mean age of 66.21 ± 7.378. Top comorbidities include hypertension (71%), obesity (51%), diabetes (31%), and hypercholesterolemia (48%). 36.27% of participants had MetS at baseline, higher than the prevalence observed in NHANES for Bl/AA men without cancer (16.7%). Many had risk factors for MetS: 27% had BP &amp;gt;130/80 mmHg, 65% had fasting glucose levels &amp;gt; 100mg/dl, 27% had HDL level &amp;lt;40 mg/dl, 17% had triglyceride levels &amp;gt; 150 mg/dl and 73% had waist circumference &amp;gt; 101.6cm(40 inches). When assessing physical activity at baseline 39% were active, 28% were moderately active and 33% were insufficiently active. 41% of those with MetS were insufficiently active. PA and MetS were not significantly associated X2(2, N = 98) = 0.370, P = 0.833. However, among MetS components, PA was significantly associated with high BP, X2(2, N = 108) = 10.51, P = 0.0052. Conclusion: Data reflects the value of supporting AAPCS in lifestyle changes to increase PA and to improve the burden of CV disease and PC recurrence risk. Few efforts have addressed lifestyle among AAPCS, despite high PC prevalence. Future reports will examine other factors associated with MetS and prostate cancer such as dietary intake and body composition. Citation Format: Meheret B. Gebreegziabher, Patricia Sheean, Paula Papanek, Alexis Vistcky, Awoyinka Iwalola, Anjishnu Banerjee, Toni Uhrich, Margaret Tovar, Miracle Powell, Sandra Contreras, Kathleen O'Connell, Melinda Stolley. Prevalence of metabolic syndrome and its association with physical activity in African American prostate cancer survivors at baseline of Men Moving Forward, a lifestyle intervention program [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A021.

Combined radiotherapy and hormone therapy in unfavorable intermediate risk prostate cancer

Background. Currently, the group of intermediate risk prostate cancer (PC) includes 2 subgroups - favorable and unfavorable intermediate risk according to the National Comprehensive Cancer Network (NCCN) classification. The optimal scope of therapy is not defined for the unfavorable intermediate risk subgroup. In particular, the need for and duration of hormone therapy (HT) during combined radiotherapy (CRT) have not yet been determined.Aim. To perform a comparative analysis of the efficacy and toxicity of CRT in patients with unfavorable intermediate risk treated with and without HT.Materials and methods. Eighty-four (84) patients with unfavorable intermediate risk PC were treated with CRT at the clinic of the A.F. Tsyb Medical Radiological Research Center between May 2016 and December 2020. Patients were divided into two groups: external beam radiation therapy + brachytherapy (n = 40) and external beam radiation therapy + brachytherapy + HT (n = 44). Conformal external beam radiation therapy was delivered with conventional fractionation to a total dose of 44-46 Gy and the 192Ir high-dose rate brachytherapy was delivered with a single fraction of 15 Gy. Median duration of HT consisting of gonadotropin-releasing hormone agonist was 6 months. Median age was 65.2 years (range: 49-80 years). Median follow-up was 58.1 months (range: 18.6-83.7 months).Results. With a median follow-up of 4.8 years, progression-free survival was 95 % and 97.6 % in the external beam radiation therapy + brachytherapy group and external beam radiation therapy + brachytherapy + HT group, respectively (p = 0.578). The break between treatment stages of more than 28 days was associated with a statistically significant increase in the risk of PC recurrence (p = 0.007). Overall survival for the external beam radiation therapy + brachytherapy group versus external beam radiation therapy + brachytherapy + HT group was 97.5 and 93.2 % (p = 0.376), respectively.Late genitourinary toxicity was grade I in 8 (9.5 %) patients and grade II in 1 (1.2 %) patient. Urethral stricture developed in 3 (3.6 %) patients. Late gastrointestinal toxicity was grade I in 7 (8.3 %) patients and grade II in 1 (1.2 %) patient. There were no statistically significant differences in the incidence of late complications between groups with and without HT. There was a statistically significant (p = 0.049) effect of prostate volume on the incidence of late radiation proctitis.Conclusion. There were no statistically significant differences in progression-free survival and overall survival in patients with unfavorable intermediate risk PC who received external beam radiation therapy + brachytherapy with or without HT. The incidence and severity of adverse events were acceptable and allowed patients with PC to maintain high quality of life.

Prostate-specific antigen density as a predictor of recurrence-free survival following combined hormonal-radiation therapy of localized prostate cancer

Background. Prostate cancer is amongst one of the most prevalent cancers in men worldwide. Combined hormonal-radiation therapy has become a standard of care for localized prostate cancer definitive treatment. As many as 30 % of men are at risk for disease progression within 10 years following radical treatment.Aim. To assess the significance of prostate-specific antigen (PSA) density as a predictor of recurrence-free survival following combined hormonal-radiation therapy in patients with localized prostate cancer.Materials and methods. We conducted a retrospective study of 272 patients with clinically localized prostate cancer treatment results who received combined hormonal-radiation therapy between January 1996 and December 2016.Results. On the basis of our study, we confirmed high prognostic value of PSA density among patients with localized prostate cancer who received combined hormonal-radiation treatment. We utilized ROC-analysis in order to determine the threshold value of the PSA density index – 0.376 ng/ml/cm3, exceeding of which was associated with statistically significant reduction in the recurrence-free survival rate. The area under the curve was 0.711 (95 % confidence interval 0.653–0.764; p &lt;0.0001). The risk of recurrence increased with rising of PSA density.Conclusion. PSA density has proven to be a reliable tool for assessing the risk of prostate cancer recurrence among patients with localized prostate cancer who have undergone combined hormonal-radiation therapy.

Serum Paraoxonase-1 Activity and the Risk of Prostate Cancer Recurrence in Patients Treated with Radiotherapy.

The antioxidant paraoxonase-1 (PON1) may be involved in the response to radiation-induced oxidative stress and possibly prevent cell apoptosis. The correlation of PON1 with the risk of cancer recurrence after radiotherapy (RT) is not yet explored. We investigated changes in the activity of PON1 in patients with prostate cancer (PCa) undergoing RT, and the relation of PON1 activity to the risk of recurrence after RT. We included 56 men with PCa. Blood samples were obtained before irradiation and after the completion of RT. Patients were followed for an average of 51.2 months. Each case of biochemical recurrence was confirmed with biopsy. The control group was composed of 60 healthy men. There was no significant difference in PON1 activity between the control group and patients pre-radiotherapy. Irradiation was associated with a significant decrease in PON1 activity. Patients with PCa recurrence had significantly higher serum PON1 activity than those recurrence-free, both before and after RT. PON1 activity was a predictor of PCa recurrence, with sensitivity over 80% and specificity over 64%. Our results suggest that PON1 activity may be a predictor of PCa recurrence risk after RT. Studies with a larger number of patients and longer follow-up are needed to confirm this hypothesis.

Both AA genotype of rs165599 and Val/Val genotype of rs4680 in COMT are associated with an increased risk of recurrence of prostate cancer

IntroductionCOMT expression was reported to be associated with the recurrence of prostate cancer. Furthermore, it has been shown that rs165599 SNP in the 3’UTR of COMT affects the interaction between miR-138 and COMT, while another polymorphism (rs4680) located in the gene of COMT also affects its expression. Here, we explored the combined effect of rs165599 and rs4680 .Material and methodsKaplan-Meier analysis was performed to analyze the PSA-progression-free survival of prostate cancer patients carrying different genotypes of rs165599 and rs4680 SNPs. IHC and Western blot were used to evaluate the expression of COMT. Real-time PCR was carried out to examine the expression of miR-138 and COMT mRNA. Luciferase assay was performed to explore the inhibitory role of miR-138 in the expression of COMT carrying different genotypes.ResultsThe PSA-progression-free survival was significantly increased in prostate cancer patients carrying the rs165599-AA + rs4680-Val/Val genotype. In concordance with this, the expression of COMT was remarkably elevated in the tissue samples collected from prostate cancer patients carrying the rs165599-AA + rs4680-Val/Val genotype. Luciferase assay demonstrated that COMT-G at rs165599 was effectively suppressed by miR-138 through binding to the 3’ UTR of COMT-G. Furthermore, COMT expression was notably suppressed by miR-138 precursors in primary prostate cancer cells carrying GG genotype at rs165599.ConclusionsThe findings of this study demonstrated that the carriers of AA genotype of rs165599 and Val/Val genotype of rs4680 showed an increased risk of prostate cancer recurrence, and these two polymorphisms may jointly function as a novel biomarker for the prognosis of prostate cancer recurrence.

Tumour microenvironment markers predict risk of prostate cancer recurrence.

Tumour microenvironment markers predict risk of prostate cancer recurrence.

Retzius-sparing versus standard robotic-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

Robotic-assisted laparoscopic prostatectomy (RALP) is widely used to surgically treat clinically localizedprostate cancer. It is typically performed using an approach (standard RALP) that mimics open retropubic prostatectomy by dissecting the so-called space of Retzius anterior to the bladder. An alternative, Retzius-sparing (or posterior approach) RALP (RS-RALP) has been described, which is reported to have better continence outcomes but may be associated with a higher risk of incomplete resection and positive surgical margins (PSM). To assess the effects of RS-RALP compared to standard RALP for the treatment of clinically localized prostate cancer. We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to June 2020. We applied no restrictions on publication language or status. We included trials where participants were randomized to RS-RALP or standard RALP for clinically localized prostate cancer. Two review authors independently classified and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery six and 12 months after surgery, potency recovery 12 months after surgery, positive surgical margins (PSM),biochemical recurrence-free survival (BCRFS), and urinary and sexual function quality of life. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. Our search identified sixrecords of five unique randomized controlled trials, of which twowere published studies, one was in press,and twowere abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. Mean age of participants was 64.6 years and mean prostate-specific antigen was 6.9 ng/mL. About 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1 % had cT2c disease. Primary outcomes RS-RALP probably improves continence within one week after catheter removal (risk ratio (RR) 1.74, 95% confidence interval (CI) 1.41 to 2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at thistime point,this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06 to 1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750per 1000 men undergoing standard RALP are continent at thistime point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47 to 4.17; studies = 2; participants = 230; very low-certainty evidence). Secondary outcomes There is probably little to no difference in continence recovery at 12 months after surgery (RR 1.01, 95% CI 0.97 to 1.04; I2 = 0%; studies = 2; participants = 222; moderate-certainty evidence). Assuming 982per 1000 men undergoing standard RALP are continent at thistime point, this corresponds to 10 more men per 1000 (29 fewer to 39 more) reporting continence recovery. We are very uncertain about the effect of RS-RALPon potency recovery 12 months after surgery (RR 0.98, 95% CI 0.54 to 1.80; studies = 1; participants = 55; very low-certainty evidence). RS-RALP may increase PSMs (RR 1.95, 95% CI 1.19 to 3.20; I2 = 0%; studies = 3;participants = 308; low-certainty evidence) indicating a higher risk forprostate cancer recurrence. Assuming 129per 1000 men undergoing standard RALP have positive margins, this corresponds to 123 more men per 1000 (25 more to 284 more) with PSMs. We are very uncertain about the effect of RS-RALP on BCRFScompared to standard RALP (hazard ratio (HR) 0.45, 95% CI 0.13 to 1.60; I2 = 32%; studies = 2; participants = 218; very low-certainty evidence). Findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to six months after surgery. Continence outcomes at12 months may be similar. Downsides of RS-RALP may be higher positive margin rates. We are very uncertain about the effect on BCRFS and potency outcomes. Longer-term oncologic andfunctional outcomes are lacking, and nopreplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy.

Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI. We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation-treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable-adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT). Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow-up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87-3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24-1.03; P-interaction = .002), though neither association reached statistical significance. Similar patterns of ADT-stratified associations were observed for PPAT and SFA. Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.

Abstract C009: Post-diagnostic statin and metformin use and risk of biochemical recurrence risk among Black and White men diagnosed with prostate cancer at the Veterans Health Administration

Abstract BACKGROUND: Prostate cancer is the most common cancer among men in the United States. Black men represent a high-risk group that is more likely to be both diagnosed with and experience adverse prostate cancer outcomes. Both statins (to reduce cholesterol) and metformin (to treat diabetes) have been hypothesized to reduce the risk of biochemical recurrence (BCR), a clinically important outcome, among men with prostate cancer. However, few studies have examined this association specifically in Black men. Because Black men are at greater risk for adverse prostate cancer outcomes, the potential of commonly used medications, including metformin and statins, to reduce this increased risk needs to be investigated. Here, we have examined the potential of metformin and statins to reduce risk of prostate cancer recurrence in a racially-diverse cohort of men diagnosed with prostate cancer at the Veterans Health Administration (VHA). METHODS: Our cohort consisted of 20,359 Black and 52,004 White men that were diagnosed with prostate cancer between 1997-2009 at the VHA and received definitive treatment for prostate cancer (radical prostatectomy or radiation). Statin use and metformin use were defined as any statin or metformin prescription after prostate cancer diagnosis. BCR was defined using established definitions. (For men treated with radical prostatectomy, BCR was defined as a PSA of 0.2 ng/mL or higher for two consecutive assays without treatment. For men treated with radiation, BCR was defined as rise of 2 ng/ mL or more above the nadir achieved after radiation therapy.) Cox proportional hazard models adjusted for age at diagnosis, prostate cancer grade, prostate cancer stage, and locale (rural vs. urban) were used to assess the association between statin and metformin use. Statin and metformin use were analyzed in separate models, stratified by race. RESULTS: Statin use (69.9% of Black men; 75.4% of White men) and metformin use (29.4% of Black men; 24.3% of White men) were prevalent in our cohort. The mean BCR-free survival time was 5.7 years and 6.0 years in Black and White men, respectively, with 16.6% of Black men and 13.8% of White experiencing a BCR. Statin use was associated with a significantly reduced risk of BCR in the cohort as a whole (Hazard Ratio (HR): 0.87; 95% Confidence Interval (CI): 0.83, 0.91), Black men (HR: 0.84; 95% CI: 0.77, 0.90), and White men (HR:0.89; 95% CI: 0.84, 0.95). We observed no association between metformin use and risk of BCR [Overall (HR: 1.05; 95% CI: 1.00, 1.10), Black men (HR: 1.00; 95% CI: 0.93, 1.08), White men (HR: 1.05; 95% CI: 1.00. 1.11)]. CONCLUSION: Post-diagnostic statin use may reduce the risk of BCR in both Black and White men. This is one the few studies to examine statin use and metformin use specifically in Black men with prostate cancer. Importantly, because all patients treated at the VHA receive care regardless of insurance status, this study was able to control for socioeconomic status in ways other studies are unable. Citation Format: Saira Khan, Bettina Drake. Post-diagnostic statin and metformin use and risk of biochemical recurrence risk among Black and White men diagnosed with prostate cancer at the Veterans Health Administration [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C009.

A Pilot retrospective analysis of alpha-blockers on recurrence in men with localised prostate cancer treated with radiotherapy

While alpha-blockers are commonly used to reduce lower urinary tract symptoms in prostate cancer patients receiving radiotherapy, their impact on response to radiotherapy remains unknown. Therefore, this pilot study aimed to retrospectively determine if alpha-blockers use, influenced response to radiotherapy for localised prostate cancer. In total, 303 prostate cancer patients were included, consisting of 84 control (alpha-blocker naïve), 72 tamsulosin and 147 prazosin patients. The main outcomes measured were relapse rates (%), time to biochemical relapse (months) and PSA velocity (ng/mL/year). Recurrence free survival was calculated using Kaplan-Meier analysis. Prazosin significantly reduced biochemical relapse at both two and five-years (2.72%, 8.84%) compared to control (22.61%, 34.52%). Recurrence free survival was also significantly higher in the prazosin group. This remained after multivariable analysis (HR: 0.09, 95% CI: 0.04–0.26, p < 0.001). Patients receiving prazosin had a 3.9 times lower relative risk of biochemical relapse compared to control. Although not statistically significant, tamsulosin and prazosin extended recurrence free survival by 13.15 and 9.21 months respectively. We show for the first time that prazosin may reduce risk of prostate cancer recurrence and delay time to biochemical relapse and provides justification for prospective studies to examine its potential as an adjunct treatment option for localised prostate cancer.

Association between prostate-specific antigen change over time and prostate cancer recurrence risk: A joint model.

Background:Prostate specific antigen (PSA) is an important biomarker to monitor patients after treated with radiation therapy (RT). The aim of this study is to evaluate the relationship between the PSA data and prostate cancer recurrence using the joint modeling.Methods:This historical cohort study was performed on 422 prostate cancer patients. Inclusion criteria included: patients with localized prostate cancer referring to Cancer Institute in Tehran (Iran) from 2007 to 2012, and under radiation therapy. Joint model has two components or sub-models. We showed the results by parameter estimating the longitudinal sub-model and survival sub-model. EM algorithm, Newton-Gauss and Gauss-Hermit law were used for final model parameters. R software version 3.2 was used for statistical analysis.Results:In this study, considering the inclusion and exclusion criteria, out of 422 patients, the data on 314 cases were selected for analysis and the main result of joint model was obtained. PSA directly and significantly was associated with recurrence risk, therefore increasing 2.6 ml/lit PSA (one unit in transformed PSA) increases 39% recurrence risk (95% CI for RR: 1.09-1.77). Also, slope of PSA trend has significant association with prostate cancer recurrence risk (95% CI for RR: 1.05-1.41).Conclusion:This study showed a significant relationship between PSA, and its slope with the recurrence risk by joint model, with regard to the pathological, demographic and clinical features in the Iranian population.

Smoking history, intensity, and duration and risk of prostate cancer recurrence among men with prostate cancer who received definitive treatment

PurposeTo examine the association of smoking history and multiple measures of smoking intensity and duration with risk of biochemical recurrence in men treated for prostate cancer. MethodsWe conducted a prospective cohort study of 1641 men (773 ever-smokers) treated with radical prostatectomy or radiation between 2003 and 2010. The association between ever-smoking and risk of biochemical recurrence was examined using Cox Proportional Hazards models with adjustment for confounders. Among ever-smokers, we further assessed the association between multiple measures of smoking duration and intensity and risk of biochemical recurrence. ResultsIn the full cohort, we observed no association between ever-smoking and risk of biochemical recurrence. However, among ever-smokers, a smoking duration of greater than or equal to 10 years was significantly associated with biochemical recurrence (hazard ratio: 2.32, 95% confidence interval: 1.01, 5.33). Our results also suggested that greater than or equal to 10 pack-years of smoking may be associated with an increased risk of biochemical recurrence (hazard ratio: 1.75, 95% confidence interval: 0.97, 3.15). No association was observed between packs smoked per day or years since smoking cessation (among former smokers) and risk of biochemical recurrence. ConclusionSmoking duration is a significant predicator of biochemical recurrence among men with prostate cancer who are current or former smokers.

Multivitamin use and risk of prostate cancer recurrence: Data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE).

70 Background: Multivitamin (MV) use is common among men with prostate cancer (PCa). Yet, data on MV use and risk of PCa recurrence are limited. Methods: We conducted a prospective study among 1,373 men with non-metastatic PCa to examine whether MV use after diagnosis was associated with risk of recurrence. Participants completed a comprehensive lifestyle survey a median of 2 y after diagnosis and were followed through 2016. We defined an event of recurrence as the first of the following: PCa death, bone metastasis from PCa, biochemical recurrence, or initiation of secondary treatment. Multivariate Cox Proportional Hazards regression models were used to calculate hazards ratios (HRs) and 95% confidence intervals (CI) for the association between MV use and PCa recurrence. We adjusted for time between diagnosis and the survey, age at diagnosis, Gleason grade, clinical T-stage, PSA at diagnosis, smoking, BMI, walking pace, and primary treatment. We also explored whether age at diagnosis, BMI, time since diagnosis, smoking, or clinical features (grade, stage, treatment) modified the association between MV use and recurrence. Results: We observed 142 events of PCa recurrence over a median follow-up of 10 y; 858 (62%) men were current MV users, 216 (16%) were past users, and 299 (22%) were never users. Overall, MV use was not associated with risk of PCa recurrence (current vs. never HR: 0.69; 95% CI: 0.45, 1.07; p-trend: 0.09). However, long-term MV users (≥10 y; n = 396) had a 56% lower risk of PCa recurrence compared to never users (HR: 0.44; 95% CI: 0.25, 0.78; p-trend: 0.006). Additionally, treatment modified the association between MV use and risk of PCa recurrence ( p-interaction: 0.02). Among the 845 men who had a radical prostatectomy (RP), current MV users had a 44% lower risk of PCa recurrence compared to past/never users (HR: 0.56; 95% CI: 0.34, 0.91; p-value: 0.02). MV use was not associated with risk of PCa recurrence among the 441 men who did not have a RP. Conclusions: Long-term MV use may be associated with lower risk of PCa recurrence.

The association of weight change in young adulthood and smoking status with risk of prostate cancer recurrence.

The decades before prostate cancer diagnosis represent an etiologically relevant time period for prostate cancer carcinogenesis. However, the association of weight gain in young adulthood with subsequent biochemical recurrence among men with prostate cancer is not well studied, particularly among smokers. We conducted a prospective cohort study of 1,082 men with prostate cancer and treated with either radical prostatectomy or radiation between 2003 and 2010. The association of weight at age 20, weight at age 50 and weight change from age 20 to age 50 with biochemical recurrence was assessed using Cox Proportional Hazards with adjustment for confounders. Stratum-specific hazard ratio (HR) estimates by smoking status were evaluated. In the overall cohort, weight at age 20 (HR per 30 kg: 1.56, 95% confidence interval (CI): 1.02, 2.38, p-trend: 0.039), weight at age 50 (HR per 30 kg: 1.80, 95% CI: 1.32, 2.47, p-trend: <0.001) and weight change from age 20 to age 50 (HR per 30 kg: 1.84, 95% CI: 1.24, 2.74, p-trend: 0.003) were associated with biochemical recurrence. In stratified analyses, weight change from age 20 to age 50 was significantly associated with biochemical recurrence only in former smokers (HR per 30 kg: 3.87, 95% CI: 1.88, 8.00, p-trend: <0.001) and ever smokers (HR per 30 kg: 2.38, 95% CI: 1.27, 4.45, p-trend: 0.007). No significant association was observed between weight gain in young adulthood and biochemical recurrence in never smokers. Our study adds further evidence that weight gain during early adult years conveys long-term risk for adverse cancer outcomes.

Current or recent smoking is associated with more variable telomere length in prostate stromal cells and prostate cancer cells.

Current and recent smoking have been associated with a greater risk of prostate cancer recurrence and mortality, though the underlying mechanism is unknown. To determine if telomere shortening, which has been associated with poor outcomes, may be a potential underlying mechanism, we prospectively evaluated the association between smoking status and telomere length in 567 participants in the Health Professionals Follow-up Study, who were surgically treated for prostate cancer. Using tissue microarrays (TMA), we measured telomere length in cancer and benign tissue, specifically stromal cells in the same TMA spot using a telomere-specific fluorescence in situ hybridization assay. Smoking status was collected via questionnaire 2-years before diagnosis. Adjusting for age, pathologic stage and grade, the median and standard deviation of the per-cell telomere signals were determined for each man for stromal cells and cancer cells by smoking categories. In sub-analyses, we restricted to men without major co-morbidities diagnosed before prostate cancer. Overall, there were no associations between smoking status and telomere length or variability in stromal cells or cancer cells. However, among men without comorbidities, current smokers and former smokers who quit <10 years ago had the most variable telomere length in stromal cells (29.3% more variable than never smokers; P-trend = 0.0005) and in cancer cells (27.7% more variable than never smokers; P-trend = 0.05). Among men without comorbidities, mean telomere length did not differ by smoking status in stromal cells or cancer cells. Telomere variability in prostate cells may be one mechanism through which smoking influences poor prostate cancer outcomes.

Chemoprevention with isothiocyanates – From bench to bedside

Isothiocyanates (ITCs) are naturally occurring hydrolization products from glucosinolates (GLSs) in brassicaceae and in epidemiological studies their intake has been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of ITCs, mainly related to a.) detoxification (induction of phase II enzymes), b.) anti-inflammatory properties by down-regulation of NFkappaB activity, c.) cyclin-mediated cell cycle arrest and d.) epigenetic modulation by inhibition of histone deacetylase activity. First prospective clinical trials were promising in patients with risk of prostate cancer recurrence. The glutathione-S-transferase gene expression seems to play a major role in the individual susceptibility towards ITCs. Safety issues are widely unclear and should be more addressed in future studies because ITCs can, in low concentrations, compromise the function of human immune cells and might impair genome stability.

Obesity and prostate cancer.

To investigate the association between obesity and prostate cancer (PCa). Obesity has been proposed to be involved in the pathogenesis of PCa through different biological mechanisms that include deregulation of the insulin axis, sex hormone secretion, adipokines signaling, and oxidative stress. Hypertrophic peritumoral adipocytes may also facilitate the local spread of PCa through the chemo-attraction of tumor cells. Clinical studies demonstrate that obesity might have clinical implications also in disease detection and management. Obese men have been shown to be less likely to be diagnosed with early-stage disease. Moreover, they are at increased risk of experiencing upgrading and upstaging when managed with active surveillance. However, the association between obesity and the risk of PCa recurrence and mortality after radical treatment is still debated. Obesity may facilitate the development and progression of PCa trough different biologic mechanisms that may pose obese men at higher risk of advanced and high-grade disease. However, the association between obesity and long-term oncologic outcome after radical treatments appears unclear.

BMI and serum lipid parameters predict increasing risk and aggressive prostate cancer in Chinese people.

ObjectivesTo determine if obesity and serum lipid parameters are associated with increased risk and more aggressive prostate cancer in Chinese populationMaterials and MethodsWe conducted a retrospective cohort analysis including 3102 patients. Kruskal-Wallis test for continuous variables and the chi-squared tests for categorical variables were used for univariate comparison of the differences in patient characteristics across BMI categories between different groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for the association between prostate cancer and the various patient characteristics. Multivariable Cox proportional hazards regression was performed to assess the risk of prostate cancer recurrenceResults974 consecutive men were diagnosed as prostate cancer and 700 patients subsequently received radical prostatectomy immediately, and 1031 patients were pathologically diagnosed as biopsy negative. The level of low-density-lipoprotein cholesterol (LDL-c) and total cholesterol was significantly higher and the high-density-lipoprotein cholesterol (HDL-c) level is much lower in prostate cancer patients. Patients with low level of HDL-c, who subsequently received radical prostatectomy, had increased risk of high risk disease. In addition, patients with normal weight were less likely to develop a biochemical recurrence. Combined analysis revealed that obese patients had significantly higher rates of PSA recurrence over time than nonobese patients.ConclusionsIn our study, lipid parameters are supposed to be associated with prostate cancer risk and aggressiveness. Obese men are at increased risk of PSA recurrence after radical prostatectomy.