Non-prostate Cancer Mortality Research Articles

Comparison of Intermittent and Continuous Androgen Deprivation Therapy in Prostate Cancer Patients: An Up-to-Date Meta-analysis for Urologists and Medical Providers.

Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancer-specific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias. A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancer-specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR=0.94 [0.76-1.17]). These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.

Risk of severe late toxicity after radiotherapy following radical prostatectomy - a nationwide study.

To estimate the long-term risks of severe late toxicities for radiation therapy (RT) following radical prostatectomy (RP) in an unselected nationwide cohort, as severe side-effects are rare but may occur years later. The study population comprised all men undergoing RP between 1997 and 2016 in the Prostate Cancer database Sweden (PCBaSe) (n = 40 962). By (1:2) matching, two cohorts were created: 2789 men exposed to postoperative RT and 5578 unexposed men with comparable age, comorbidities, and year of surgery. Cumulative incidences and rate ratios were calculated for the following outcomes: symptoms and interventions of the urinary or intestinal tract demanding inpatient care, secondary malignancies, and non-prostate cancer mortality. The largest differences were seen for late toxicities affecting the urinary tract. The 10-year cumulative incidences among those exposed to postoperative RT vs the RP-only group were: 17.8% vs 10.5% for procedures of the urinary tract (difference 7.3%, 95% confidence interval [CI] 4.4 to 10.3; relative risk [RR] 1.74, 95% CI 1.47 to 2.05); 6.0% vs 1.2% for haematuria (difference 4.8%, 95% CI 3.1 to 6.5; RR 6.50, 95% CI 4.31 to 10.10); and 2.4% vs 1.1% for bladder cancer (difference 1.4%, 95% CI 0.4 to 2.3; RR 2.71, 95% CI 1.72 to 4.33). The groups were similar regarding intestinal toxicity, other secondary malignancies, and non-prostate cancer mortality. Adjustments for preoperative tumour risk factors did not importantly affect the rate ratios. Severe late toxicity after postoperative RT following RP predominately affects the bladder and can appear many years after RT.

EDITORIAL COMMENT

In this interesting study, an automatically calculated electronic comorbidity measure, the Care Assessment Needs (CAN) score, was studied as predictor of life expectancy in a huge Veterans Health Administration (VHA) patient sample. 1 N. N. et al. Using an automated electronic health record score to estimate life expectancy in men diagnosed with prostate cancer in the Veterans Health Administration. Urology. 2021; ([in press]) Google Scholar The score was originally designed to estimate short-term risks of hospitalization and mortality. The authors demonstrated a strong association of the CAN score with medium-term mortality after prostate cancer diagnosis. 1 N. N. et al. Using an automated electronic health record score to estimate life expectancy in men diagnosed with prostate cancer in the Veterans Health Administration. Urology. 2021; ([in press]) Google Scholar Although this instrument may be automatically available in VHA patients, its high complexity may hinder its routine use in different institutions. Instruments predicting life expectancy to support treatment selection in men with early prostate cancer should not only be accurate but also simple to use. 2 Daskivich TJ Kwan L Dash A et al. Weighted versus unweighted Charlson score to predict long-term other-cause mortality in men with early-stage prostate cancer. Eur Urol. 2014; 66: 1002-1009 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar In contrast to some contrary claims, 3 Walz J Gallina A Perrotte P et al. Clinicians are poor raters of life-expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer. BJU Int. 2007; 100: 1254-1258 Crossref PubMed Scopus (113) Google Scholar at least in candidates for radical prostatectomy, clinicians are probably able raters of life expectancy. In our radical prostatectomy series, even patients with the highest risk of competing mortality (age-adjusted Charlson score of 6 or higher, comprising only 4% of the sample) had a 10-year non-prostate cancer mortality rate of only 40% 4 Froehner M. Patient reported vs claims based measures of health for modeling life expectancy in men with prostate cancer. Letter. J Urol. 2021; 205: 1235-1236 Crossref Scopus (1) Google Scholar and the 50% level was not reached before narrowly 14 years. Complex tools requiring comprehensive data collection will probably not change routine decision making in candidates for radical prostatectomy regardless of their accuracy. If the risk classifications were, however, automatically calculated and readily available, there may be a different situation. Because of the huge sample size and the detailed information collected, the impressive data source used in this study 1 N. N. et al. Using an automated electronic health record score to estimate life expectancy in men diagnosed with prostate cancer in the Veterans Health Administration. Urology. 2021; ([in press]) Google Scholar should encourage further studies, for instance predicting 90-day mortality in vulnerable candidates for radical cystectomy.

Dynamics of conditional survival and risk factors in androgen deprivation therapy for prostate cancer using a multi-institutional Japan-wide database.

The objectives of this study were to analyze the conditional survival and prognostic factors in androgen deprivation therapy for prostate cancer using the Japan Study Group of Prostate Cancer database. Data on patients treated with primary androgen deprivation therapy between 2001 and 2003 from a nationwide database of the Japan Study Group of Prostate Cancer were used. The conditional 5-year progression-free rate, cancer-specific survival and overall survival, as well as the conditional mortality owing to prostate cancer and other causes were calculated as per subgroups. Prognostic factors for progression-free rate, cancer-specific survival and overall survival at each time after androgen deprivation therapy initiation were calculated using the Cox proportional hazards model. The conditional 5-year progression-free rate and cancer-specific survival, but not overall survival, gradually increased with time. The prognostic impact of stageIV characteristics (T4, N1 and M1) changed over time; however, the prognostic impact of the Gleason score remained unchanged. In the subgroup analysis, prostate-specific mortality risk reduced over time in patients with stageIV prostate cancer, whereas non-prostate cancer mortality increased over time in elderly patients. Information regarding conditional survival and mortality obtained in this study would provide a benchmark for physicians and cancer survivors.

Adherence to Mediterranean Diet, Physical Activity and Survival after Prostate Cancer Diagnosis.

Despite the considerable number of studies investigating the Mediterranean diet in prostate cancer (PCa) etiology, very few focused on cancer survival. We assessed the pre-diagnostic diet and physical activity in a cohort of 777 men with PCa diagnosed between 1995 and 2002 in north-eastern Italy; adherence to the Mediterranean diet was evaluated through the Mediterranean Diet Score (MDS). Hazard ratios (HR) of death with confidence intervals (CI) were estimated using the Cox model, adjusting for potential confounders. During 10 years of follow-up, 208 patients (26.8%) died, 75 (9.7%) due to PCa. Patients reporting MDS ≥ 5 showed a higher overall survival than those with MDS < 5 (HR = 0.74; 95% CI: 0.56–0.99). Although high physical activity was not significantly associated with overall survival (HR = 0.79; 95% CI: 0.59–1.07), the HR for all-cause death was the lowest (HR = 0.58; 95% CI: 0.38–0.90) for men reporting MDS ≥ 5 and high physical activity compared to those reporting MDS < 5 and low/moderate physical activity. No association emerged for PCa specific survival. Study findings support the beneficial impact of pre-diagnostic adherence to the Mediterranean diet and physical activity on overall survival; they are mainly driven by risk reduction in non-prostate cancer mortality, which however accounts for about 80% of death in men with PCa.

Quantifying the Relationship Between Increasing Life Expectancy and Nonprostate Cancer Mortality After Radical Prostatectomy

OBJECTIVETo investigate the relationship between increasing life expectancy and nonprostate cancer (competing) mortality after radical prostatectomy. PATIENTS AND METHODSWe studied a single-center sample of 6809 consecutive patients who underwent radical prostatectomy between 1992 and 2016 with a median age of 65 years and a median follow-up of 7.9 years. Multivariate competing risk analyses were performed with competing mortality as endpoint. Linear trends over the years of surgery for 5-year competing mortality rates and for mean ages were calculated using linear regression analyses. We estimated the number of live years gained over time using a heuristic model-based calculation: (hazard ratio year of surgery) 24 calendar years × (hazard ratio age at surgery) gained life years = 1. RESULTSAfter controlling for age, nonprostate cancer mortality decreased significantly during the observation period. Accumulated over the 24 years, this decrease of mortality corresponded to the effect of 6.3 years of calendric age. Most of the decrease in nonprostate cancer mortality (predominantly attributable to noncancer causes of death) was seen in patients aged 65 years or older (8.1 years gained), whereas there was only a marginal decrease in patients younger than 65 years (only 1 year gained). The decrease in nonprostate cancer mortality was accompanied by a slight increase of mean age at surgery (2.7 years) that did not nearly compensate the decreasing risk. CONCLUSIONClinicians should be aware of the decreasing competing mortality risk in elderly candidates for radical prostatectomy in order to avoid undertreatment.

PT375 - Relationship between socioeconomic factors and non-prostate cancer mortality after radical prostatectomy

PT375 - Relationship between socioeconomic factors and non-prostate cancer mortality after radical prostatectomy

The Veterans Affairs Disparity Paradox: Racial Disparities Among a Cohort of American Military Veterans with Prostate Cancer

Black men with prostate cancer have historically been found to have worse outcomes compared to other racial/ethnic groups. This finding has primarily been attributed to differences in genetics, health care access, and socioeconomic status. We sought to validate this relationship between race and prostate cancer specific mortality (PCSM) in a large national cohort of American veterans. We used a nationwide database of the Veterans Health Administration (VHA) by means of the VA Informatics and Computing Infrastructure (VINCI). Our initial query captured 82,886 patients who were diagnosed with prostate cancer from 2000 to 2015 and had received radiation therapy as part of their initial treatment. To control for possible confounders, patients who received brachytherapy, surgery, or had metastatic disease at diagnosis were excluded. Covariates included age at diagnosis, T stage, Gleason score, PSA at diagnosis, administration of ADT, Charlson Comorbidity Index (CCI) score, tobacco/alcohol history, marital status, employment status, and median income. Patients who lacked data for covariates were excluded. We compared baseline characteristics between blacks and other racial/ethnic groups with Pearson’s chi-squared and Mann-Whitney U tests. We compared PCSM and non-prostate cancer mortality (NPCM) between groups using multivariable Cox proportional hazards models. Our final study cohort included 27,753 patients, of which 8,453 (30.5%) were black. At time of diagnosis, blacks were younger (64 vs 67, p<0.001), had a higher PSA (12.6 vs 10.2, p<0.001), and were more likely to have a CCI score of 2+ (24.5% vs 19.8%, p<0.001). Additionally, they were more likely to have T1 disease (72.6% vs 62.3%, p<0.0001) and slightly more likely to receive ADT (47.5% vs 46.1%, p=0.037). Blacks were less likely to have Gleason 8+ disease (20.6% vs 22.5%, p<0.001). Controlling for potential confounders, we found improved PCSM among blacks (HR 0.86, 95% CI 0.77 to 0.97, p=0.012). Increasing age, PSA, T stage, Gleason score, and CCI score were associated with worse PCSM. In addition to improved PCSM, we also found that black patients had improved NPCM compared to other racial/ethnic groups (HR 0.812, 95% CI 0.76 to 0.87, p<0.0001). Our discovery of improved prostate cancer specific mortality and non-prostate cancer mortality among black veterans demonstrates a unique racial disparity paradox that has not been seen in the general population. Further research is required to determine if our results are driven by systematic differences in the cohort or in VHA care delivery.

MP22-09 ASSOCIATION BETWEEN ANDROGEN-DEPRIVATION THERAPY AND NON-PROSTATE CANCER MORTALITY AMONG MEN WITH NON-METASTATIC PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy1 Apr 2018MP22-09 ASSOCIATION BETWEEN ANDROGEN-DEPRIVATION THERAPY AND NON-PROSTATE CANCER MORTALITY AMONG MEN WITH NON-METASTATIC PROSTATE CANCER Christopher Wallis, Raj Satkunasivam, Sender Herschorn, Calvin Law, Arun Seth, Ronald Kodama, Girish Kulkarni, and Robert Nam Christopher WallisChristopher Wallis More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , Sender HerschornSender Herschorn More articles by this author , Calvin LawCalvin Law More articles by this author , Arun SethArun Seth More articles by this author , Ronald KodamaRonald Kodama More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , and Robert NamRobert Nam More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.720AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) has been associated with cardiovascular risk factors and the development of cardiovascular disease in men with metastatic prostate cancer. The effect of ADT on non-prostate cancer mortality is unknown among patients with non-metastatic prostate cancer. METHODS We performed a population-based, retrospective cohort study of men treated with surgery or radiotherapy for non-metastatic prostate cancer in Ontario, Canada from 2002-2009. ADT exposure was operationalized as a time-varying binary and cumulative dose exposure. Primary and secondary outcomes were non-prostate cancer mortality and cardiovascular mortality, respectively. The Fine & Gray sub-distribution method with generalized estimating equations was used to calculate sub-distribution hazard ratios (sdHR), while accounting for competing risks. RESULTS We examined 20,651 men treated for non-metastatic prostate cancer. Median follow-up was 7.4 years. Androgen deprivation therapy was not significantly associated with non-prostate cancer mortality (sdHR 0.75, 95% CI 0.37-1.50) or cardiovascular mortality (sdHR 1.16, 95% CI 0.37-3.63) when operationalized as a binary time-varying exposure. Similar results were obtained when we examined ADT cumulative dose exposure. CONCLUSIONS Androgen deprivation therapy is not associated with non-prostate cancer mortality or cardiovascular mortality in a large, population-based cohort of men with localized prostate cancer treated by surgery or radiation therapy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e274-e275 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Christopher Wallis More articles by this author Raj Satkunasivam More articles by this author Sender Herschorn More articles by this author Calvin Law More articles by this author Arun Seth More articles by this author Ronald Kodama More articles by this author Girish Kulkarni More articles by this author Robert Nam More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP21-07 PREDICT: PROSTATE – A NOVEL PROGNOSTIC MODEL THAT ESTIMATES INDIVIDUAL SURVIVAL IN NEWLY DIAGNOSED PRIMARY NON-METASTATIC PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2018MP21-07 PREDICT: PROSTATE – A NOVEL PROGNOSTIC MODEL THAT ESTIMATES INDIVIDUAL SURVIVAL IN NEWLY DIAGNOSED PRIMARY NON-METASTATIC PROSTATE CANCER David Thurtle, David Greenberg, Hong Huang, Lui Shong Lee, Paul Pharoah, and Vincent Gnanapragasam David ThurtleDavid Thurtle More articles by this author , David GreenbergDavid Greenberg More articles by this author , Hong HuangHong Huang More articles by this author , Lui Shong LeeLui Shong Lee More articles by this author , Paul PharoahPaul Pharoah More articles by this author , and Vincent GnanapragasamVincent Gnanapragasam More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.698AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prognostic stratification is the cornerstone of management in non-metastatic prostate cancer (PCa). However, existing prognostic models are inadequate -often using treatment outcomes rather than survival, stratifying by broad heterogeneous groups and using heavily treated cohorts. To address this unmet need, we developed an individualised prognostic model which contextualizes PCa-specific mortality (PCSM) against other cause mortality, and estimates the impact of treatment on survival. METHODS Data were collated for 10,089 men diagnosed with non-metastatic PCa between 2000 and 2010 in Eastern England. These were randomly split 70:30 into model development and validation cohorts. Separate multivariable models were built for 10-year PCSM and non-prostate cancer mortality(NPCM) with fractional polynomials used to fit continuous variables and baseline hazards. Discrimination and calibration were assessed by area under the curve (AUC) and Chi-Square goodness-of-fit. A Singaporean cohort of 2546 men represented a validation set of different ethnicity and geography. RESULTS Median follow-up was 9.8years with 3276 deaths (1030 of which were PCa-specific). 19.8%, 14.1%, 34.6% and 31.5% of men underwent conservative management, prostatectomy, radiotherapy and androgen deprivation monotherapy respectively. An individualised model predicting 10-year survival outcomes was constructed combining age, PSA, histological grade group, stage and treatment which were independent prognostic factors for PCSM. Age and comorbidity were prognostic for NPCM (examples in Figure 1). The model demonstrated good discrimination and calibration in the validation cohort with no significant difference in actual and predicted PCSM (p=0.16) or overall mortality (p=0.46) and AUC 0.81 (95%CI 0.78-0.83) and 0.83 (95%CI 0.81-0.84) respectively. In the Singapore cohort (330 deaths, median f/u 5.1-years) the model performed well with <1% differences in actual and predicted mortality and AUC of 0.91 and 0.89 for PCSM and overall mortality respectively. CONCLUSIONS PREDICT:Prostate is a new individualised prognostic model to be used at diagnosis. It provides information on the potential survival benefits of treatment as an aid to patient counselling and MDT decision-making. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e264-e265 Advertisement Copyright & Permissions© 2018MetricsAuthor Information David Thurtle More articles by this author David Greenberg More articles by this author Hong Huang More articles by this author Lui Shong Lee More articles by this author Paul Pharoah More articles by this author Vincent Gnanapragasam More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Null association between androgen-deprivation therapy and nonprostate cancer mortality among older men with nonmetastatic prostate cancer

BackgroundAndrogen-deprivation therapy (ADT) has been associated with cardiovascular risk factors and the development of cardiovascular disease in men with metastatic prostate cancer. We sought to examine the effect of ADT on nonprostate cancer mortality among patients with nonmetastatic prostate cancer. MethodsWe performed a population-based, retrospective cohort study of men aged 66 years and older treated with surgery or radiotherapy for nonmetastatic prostate cancer in Ontario, Canada from 2002 to 2009 using administrative datasets (including the Ontario Cancer Registry, Ontario Drug Benefit, and Ontario Health Insurance Plan). Analysis was performed between September 2016 and April 2017. ADT exposure was operationalized as a time-varying binary and cumulative dose exposure. Primary and secondary outcomes were nonprostate cancer mortality and cardiovascular mortality, respectively. The Fine and Gray subdistribution method with generalized estimating equations was used to calculate subdistribution hazard ratios (sdHR), while accounting for competing risks. ResultsWe examined 20,651 men treated for nonmetastatic prostate cancer. Median follow-up was 7.4 years and median ADT exposure was 6.4 months. ADT was not significantly associated with nonprostate cancer mortality (sdHR = 0.75, 95% CI: 0.37–1.50) or cardiovascular mortality (sdHR = 1.16, 95% CI: 0.37–3.63) when operationalized as a binary time-varying exposure. Similar results were obtained when we examined ADT cumulative dose exposure. ConclusionsADT is not associated with nonprostate cancer mortality or cardiovascular mortality in a large, population-based cohort of older men with localized prostate cancer treated by surgery or radiation therapy.

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In the Prostate Cancer Intervention Versus Observation Trial (PIVOT), surgery was not associated with lower mortality compared with observation. However, the high competing mortality rate of approximately 33% after 10 yr among the PIVOT study population has raised concerns on the generalizability of these results. We investigated 4282 patients who underwent radical prostatectomy at our institution between 1992 and 2010 to determine which subgroups harbored a competing (non-prostate cancer) mortality risk comparable to that of PIVOT and tested several combinations of higher age and comorbidities (“worst case scenarios”) to identify subgroups reaching or even superseding the competing mortality rate of the PIVOT population. The competing mortality rate of PIVOT was not reached till an age-adjusted Charlson score of 5 or higher (corresponding to an age of 70–79 yr with diabetes with end-organ damage). Only 8.9% of patients belonged to this high-risk subgroup, and only small subgroups comprising 1–5% patients superseded the competing mortality rate among the PIVOT study population. This data underline that the results of PIVOT should be used with great caution to exclude candidates for radical prostatectomy with comorbidities from curative treatment. Patient summaryOnly <10% of patients selected for radical prostatectomy reached the competing mortality rate of approximately 33% observed in the Prostate Cancer Intervention Versus Observation Trial (PIVOT). The results of PIVOT should be used with great caution to exclude patients with concomitant diseases who seem otherwise fit for radical prostatectomy from curative treatment.

Association Between Primary Local Treatment and Non–prostate Cancer Mortality in Men With Nonmetastatic Prostate Cancer

To assess the association between local treatment modality, surgery or radiotherapy, and non-prostate cancer and cardiovascular mortality in patients treated for nonmetastatic prostate cancer, given the high competing risk of mortality in this population. We performed a population-based, retrospective cohort study of men treated for nonmetastatic prostate cancer in Ontario, Canada, from 2002 to 2009. Patients treated with surgery and radiotherapy were matched on demographics, comorbidity, and cardiovascular risk factors. The primary outcome was non-prostate cancer mortality. Outcomes were compared using the Fine and Gray subdistribution method with generalized estimating equations. We used a previously published technique to quantify the prevalence and strength of residual confounding necessary to account for observed results. We examined 5393 pairs of matched men. The 10-year cumulative incidence of non-prostate cancer mortality was higher among patients who underwent radiotherapy (12%) than surgery (8%; adjusted subdistribution hazard ratio [HR] 1.57, 95% confidence interval 1.35-1.83). Patients treated with radiotherapy also had an increased risk of cardiovascular mortality (adjusted HR 1.74, 95% confidence interval 1.27-2.37). Hypothetical residual confounders would have to be both strongly associated with non-prostate cancer mortality (HRs > 2.5) and have highly differential prevalence to nullify the observed effect. Among patients carefully matched on cardiovascular risk factors, those treated with radiotherapy had an increased risk of non-prostate cancer mortality and cardiovascular disease. Because of the observational nature of the data, the potential for confounding remains. The magnitude and prevalence of potential residual confounders required to account for differences in treatment effects for prostate cancer was quantified.

1059 - Non-prostate cancer mortality following radical prostatectomy or radiotherapy in men with localized and locally advanced prostate cancer: An analysis using propensity score matching

1059 - Non-prostate cancer mortality following radical prostatectomy or radiotherapy in men with localized and locally advanced prostate cancer: An analysis using propensity score matching

Socioeconomic disadvantage but not remoteness affects short-term survival in prostate cancer: A population-based study using competing risks.

We examined how sociodemographic, clinical and area-level factors are related to short-term prostate cancer mortality versus mortality from other causes, a crucial distinction for this disease that disproportionately affects men older than 60 years. We applied competing risk survival models to administrative data from the Queensland Cancer Registry (Australia) for men diagnosed with prostate cancer between January 2005 and July 2007, including stratification by Gleason score. The men (n=7393) in the study cohort had a median follow-up of 5 years 3 months. After adjustment, remoteness and area-level disadvantage were not significantly associated with prostate cancer mortality. However, area-level disadvantage had a significant negative relationship with hazard of death from a cause other than prostate cancer within 7 years; compared with those living in the most advantaged areas, the likelihood of mortality was higher for those in the most disadvantaged (subhazard ratio [SHR] = 1.39; 95% CI, 1.01-1.90; P = 0.041), disadvantaged (SHR = 1.51; 95% CI, 1.14-2.00; P = 0.004), middle (SHR = 1.34; 95% CI, 1.02-1.75; P = 0.034) and advantaged areas (SHR = 1.44; 95% CI, 1.09-1.89; P = 0.009). Those with Gleason score of 7 and higher had a lower hazard of prostate cancer mortality if they were living with a partner, whereas those with lower Gleason scores and living a partner had lower hazards of other-cause mortality. Understanding why men living in more disadvantaged areas have higher risk of non-prostate cancer mortality should be a priority.

Reconsidering adjuvant versus salvage radiation therapy for prostate cancer in the genomics era.

We developed a decision analysis framework to simulate the clinical choice of early adjuvant versus delayed salvage radiation therapy after radical prostatectomy. We designed a Markov decision analysis model to represent two alternative treatment approaches for prostate cancer after prostatectomy over a 10-year time horizon. The model contained individualized inputs including genomic classifier score. Sensitivity analyses were performed to evaluate model results. Observation with delayed salvage radiation is preferred according to the base case, with greater average length and quality of life. However, adjuvant therapy is preferred over observation with salvage when genomics-based estimates of recurrence are high. Model results were sensitive to genomics-based estimates of cancer recurrence and to nonprostate cancer mortality.

Diabetes mellitus is associated with elevated risk of mortality amongst patients with prostate cancer: a meta-analysis of 11 cohort studies.

Diabetes mellitus is associated with a decreased risk of prostate cancer. However, previous studies examining the associations between diabetes mellitus and prostate cancer prognosis have produced mixed results. Here, we aim to summarize the effect of diabetes mellitus on prostate cancer prognosis. We searched the database of PubMed from inception through 31 March 2014 for articles evaluating the effect of diabetes on outcome in prostate cancer patients, and a meta-analysis was conducted. A total of 11 cohort studies were included in this meta-analysis, of which seven studies were carried out to investigate whether diabetes mellitus is associated with all-cause mortality amongst those with prostate cancer, seven studies to investigate whether diabetes mellitus is associated with prostate cancer-specific mortality and two studies to investigate the relationship of diabetes mellitus and nonprostate cancer mortality. The meta-analysis results suggested that diabetes mellitus could significantly affect the incidence of all-cause mortality amongst those with prostate cancer (hazard ratio = 1.50, 95% confidence interval = 1.25-1.79). Besides, diabetes mellitus was also associated with prostate cancer-specific mortality (hazard ratio = 1.26, 95% confidence interval = 1.20-1.33) and nonprostate cancer mortality (hazard ratio = 1.83, 95% confidence interval = 1.33-2.52) separately. There was no obvious publication bias amongst the studies included. The results of this meta-analysis reveal an association of diabetes mellitus with adverse prognosis amongst those with prostate cancer. The biological basis of the association of diabetes mellitus with prostate cancer incidence and prognosis remains unclear. Doctors could pay more attention to prostate patients with pre-existing diabetes mellitus, and more aggressive treatment regimens should be considered.

Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis

Objectives: Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer. Materials and methods: We conducted a population-based cohort study of 1476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D]. Results: There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes. Conclusions: We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality.

Interaction of adjuvant androgen deprivation therapy with patient comorbidity status on overall survival after radical prostatectomy for high‐risk prostate cancer

To evaluate the impact of adjuvant hormonal therapy after radical prostatectomy on overall survival in high-risk prostate cancer patients, stratified by comorbidity status. We identified 1247 patients who underwent radical prostatectomy from 1988 to 2004 for high-risk prostate cancer, as defined by National Comprehensive Cancer Network classification. Comorbidity status was stratified by Charlson Comorbidity Index as 0, 1 or >2, as well as by the presence or absence of cardiovascular disease. Overall survival was estimated by the Kaplan-Meier method, and compared within each comorbidity category/adjuvant hormonal therapy strata with the log-rank test. Median patient age was 65 years, and the median postoperative follow up was 11.2 years. In total, 419 patients (34%) received adjuvant hormonal therapy. The distribution of Charlson Comorbidity Index was 0, 1 and ≥ 2 in 861 (69%), 244 (20%) and 142 (11%) patients, respectively. The 10-year overall survival for patients who received adjuvant hormonal therapy versus those who did not was 75% versus 82% (P=0.54) for patients with Charlson Comorbidity Index=0, 72% versus 76% (P=0.83) with Charlson Comorbidity Index=1, and 70% versus 68% (P=0.33) with Charlson Comorbidity Index ≥ 2. Meanwhile, 155 (12%) patients had cardiovascular disease, and the 10-year overall survival for patients with cardiovascular disease who received adjuvant hormonal therapy was 72%, compared with 76% without adjuvant hormonal therapy (P=0.97). On multivariate analysis, receipt of adjuvant hormonal therapy was not associated with non-prostate cancer mortality (P=0.24). Adjuvant hormonal therapy after radical prostatectomy for high-risk prostate cancer does not increase non-prostate cancer mortality, even among patients with multiple comorbidities. Additional studies are warranted to determine optimal multimodal treatment approach for high-risk patients.

Active Surveillance: The Canadian Experience With an "Inclusive Approach"

Active surveillance has evolved to become a standard of care for favorable-risk prostate cancer. This is a summary of the rationale, method, and results of active surveillance beginning in 1995 with the first prospective trial of this approach. This was a prospective, single-arm cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression (to 4+3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data. Since November 1995, 450 patients have been managed with active surveillance. The cohort included men under 70 with favorable-risk disease and men of age more than 70 with favorable- or intermediate-risk cancer (Gleason score 3+4 or PSA 10-15). Median follow-up is 6.8 years (range 1-16 years). Overall survival is 78.6%. Ten-year prostate cancer actuarial survival is 97.2%. Five of 450 patients (1.1%) have died of prostate cancer. Thirty percent of patients have been reclassified as higher-risk patients and offered definitive therapy. The commonest indication for treatment was a PSA doubling time less than 3 years (48%) or Gleason upgrading (26%). Of 117 patients treated radically, the PSA failure rate was 50%. This represents 13% of the total cohort. Most PSA failures occurred early; at 2 years, 44% of the treated patients had PSA failure. The hazard ratio for non-prostate cancer mortality to prostate cancer mortality was 18.6 at 10 years. In conclusion, we observed a very low rate of prostate cancer mortality in an intermediate time frame. Among the one-third of patients who were reclassified as higher risk and retreated, PSA failure was relatively common. However, other-cause mortality accounted for almost all of the deaths. Further studies are warranted to improve the identification of patients who harbor more aggressive disease in spite of favorable clinical parameters at diagnosis [reproduced from Klotz (1) with permission from Wolters Kluwer Health].