Changes in prostate cancer incidence,mortality and survival in relation to prostate specific antigen testing in New South Wales,Australia

BackgroundTo examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population.MethodsProstate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with “unknown” stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression.ResultsTrends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial ‘spike’ in the rates occurring in 1994, followed by a second ‘spike’ in 2008, and then a significant decrease from 2008 to 2015 (APC −6.7, 95% CI −8.2, −5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0–61.7%) in 1981–1985 to 91.3% (95% CI: 90.5–92.1%) in 2011–2015. Prostate cancer mortality rates decreased from 1990 onwards (1990–2006: APC −1.7, 95% CI −2.1, −1.2; 2006–2017: APC −3.8, 95% CI −4.4, −3.1).ConclusionsOverall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.     

Predicting prostate biopsy outcome by findings at digital rectal examination, transrectal ultrasonography, PSA, PSA density and free-to-total PSA ratio in a population-based screening setting

The study offers a retrospective analysis of the positive predictive value (PPV) of several variables, i.e. digital rectal examination (DRE), transrectal ultrasonography (TRUS), PSA value, PSA density (PSAD), and free/total PSA ratio (F/T), for the histologic outcome of 179 prostate biopsies performed within a population-based screening trial. The ratio of spared benign biopsies to missed cancers (SBB/MC) if biopsy results had been decided on the basis of single variables was also evaluated. PPV was 82.9% for DRE, 56.3% for TRUS, 26.6% for PSA (cutoff > or =4 ng/mL), 47.4% for PSA (cutoff > or =10 ng/mL), 42.0% for PSAD (cutoff 0.15), 59.2% for PSAD (cutoff 0.20), 34.9% for F/T (cutoff 0.20) and 40.0% for F/T (cutoff 0.15). SBB/MC was 121/23 for DRE, 96/12 for TRUS, 11/10 for PSA (cutoff > or =4 ng/mL), 107/34 for PSA (cutoff > or =10 ng/mL), 87/23 for PSAD (cutoff 0.15), 109/26 for PSAD (cutoff 0.20), 45/8 for F/T (cutoff 0.20) and 70/14 for F/T (cutoff 0.15). Multivariate analysis of the association with biopsy outcome showed the highest odds ratio for TRUS (13.24, 95% CI=4.4-30.7), and considerably lower values for DRE (4.17, 95% CI=2.0-8-9), PSAD (cutoff 0.20: 3.24, 95% CI=-1.8-5.7) and F/T (cutoff <0.15: 3.16, 95% CI=1.7-1.8). None of the possible variable combinations was clinically useful: the highest PPV (83.3%) was obtained with a combination of suspicious DRE/TRUS, PSAD >0.20 and F/T <0.15, which nevertheless missed 20 of 52 cancers.     

Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese

The Von Hippel-Lindau (VHL) tumor suppressor gene is a crucial regulator of the hypoxia response pathway and plays an important role in tumorigenesis, particularly in tumor growth and vascularization. We hypothesize that polymorphisms in the functional region of VHL may influence susceptibility to prostate cancer (PCa). We genotyped a potentially functional polymorphism (rs779805) in 5' UTR region of VHL in a case-control study of 665 PCa patients and 715 cancer-free controls in a Chinese population using the Taqman assay. The genetic associations between the incidence and progression of PCa were assessed by logistic regression. We observed that the rs779805 A>G polymorphism was significantly associated with risk for PCa. Compared with the AA genotype, the AG and AG/GG genotypes were associated with decreased risk of PCa (adjusted odds ratio [OR]=0.79, 95% confidence interval [CI]=0.62-0.99, and adjusted OR=0.76, 95% CI=0.61-0.95, respectively). Further, this decreased risk was more pronounced in the subgroups of nonsmokers (OR=0.73, 95% CI=0.54-0.98), nondrinkers (OR=0.70, 95% CI=0.54-0.91) and patients without family history of cancer (OR=0.72, 95% CI=0.57-0.92). In addition, the decreased risk associated with rs779805 variant genotypes (AG/GG) was more pronounced among the prostate specific antigen (PSA)>20 ng/mL subgroup (OR=0.68, 95% CI=0.49-0.95). Our findings suggest that the rs779805 A>G polymorphism in VHL may confer susceptibility to PCa in the Chinese population.     

Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer

Background/aim(s)To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT).Materials/MethodsRetrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24–36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26–267).ResultsSixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8–8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7–2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6–9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26–12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33–3.79).ConclusionA positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.     

Long-term survival of patients with prostate cancer in Martinique: Results of a population-based study

BackgroundMartinique has one of the highest incidences of prostate cancer (PCa) worldwide. We analysed overall survival (OS) among patients with PCa in Martinique, using data from a population-based cancer registry between 2005 and 2014.MethodsThe log-rank test was used to assess the statistical differences between survival curves according to age at diagnosis, risk of disease progression including Gleason score, stage at diagnosis and Prostate Specific Antigen (PSA). A multivariable Cox model was constructed to identify independent prognostic factors for OS.ResultsA total of 5045 patients were included with a mean age at diagnosis of 68.1±9.0 years [36.0 – 98.0 years]. Clinical stage was analysed in 4999 (99.1% of overall), 19.5% were at low risk, 34.7% intermediate and 36.9% at high risk. In our study, 8.9% of patients with available stage at diagnosis, were regional/metastatic cancers. Median PSA level at diagnosis was 10.4 ng/mL. High-risk PCa was more frequent in patients aged 65-74 and ≥75 years as compared to those aged <65 years (36.6% and 48.8% versus 28.7% respectively; p<0.0001). One-year OS was 96.3%, 5-year OS was 83.4 and 10-year OS was 65.0%. Median survival was not reached in the whole cohort. High-risk PCa (HR=2.32; p<0.0001), regional/metastatic stage (HR= 9.51; p<0.0001) and older age (65-74 and ≥75 years - respectively HR=1.70; and HR=3.38), were independent prognostic factors for OS (p<0.0001).ConclusionThis study provides long term data that may be useful in making cancer management decisions for patients with PCa in Martinique.     

A stochastic model for survival of early prostate cancer with adjustments for leadtime, length bias, and over-detection

To compare the survival between screen-detected and clinically detected cancers, we applied a series of non-homogeneous stochastic processes to deal with leadtime, length bias, and over-detection by using full information on detection modes obtained from the Finnish randomized controlled trial for prostate cancer screening. The results show after 9-year follow-up the hazard ratio of prostate cancer death for screen-detected cases against clinically detected cases increased from 0.24 (95% CI: 0.16-0.35) without correction for these biases, to 0.76 after correction for leadtime and length biases, and finally to 1.03 (95% CI: 0.79-1.33) for a further adjustment for over-detection. Adjustment for leadtime and length bias but no over-detection led to a 24% reduction in prostate cancer death as a result of prostate-specific antigen test. The further calibration of over-detection indicates no gain in survival of screen-detected prostate cancers (excluding over-detected case as stayer considered in the mover-stayer model) as compared with the control group in the absence of screening that is considered as the mover. However, whether the model assumption on over-detection is robust should be validated with other data sets and longer follow-up.     

Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

The diagnostic value of miRNA-141 in prostate cancer: a systematic review and meta-analysis

MiR-141 has gradually demonstrated its value in the diagnosis of prostate cancer. However, the diagnostic parameters applied in previous studies were different. This systematic review was conducted to explore the diagnostic value of miR-141 in prostate cancer. A comprehensive search of related literature in PubMed, Medline, the Cochrane Library and Embase databases was performed. Seven studies were included which assessed the diagnostic value of miR-141 in patients with prostate cancer up to October 31, 2019. Meta-disc version 1.4 and STATA software version 12.0 were used to analyze the data. The pooled sensitivity and specificity were 0.70 (95% CI 0.64~0.75) and 0.73 (95% CI 0.64~0.80), respectively. The positive likelihood ratio (PLR) was 2.88 (95% CI 1.40~5.93), and negative likelihood ratio (NLR) was 0.38 (95% CI 0.20~0.71). The pooled diagnostic odds ratio (DOR) of miR-141 for prostate cancer was observed to be 9.94 (95% CI: 2.55~38.80). The summary area under the receiver operating characteristic (ROC) curve was 0.83 (95% CI: 0.79~0.86). The results of meta-regression suggested that heterogeneity was mainly derived from patient age. The Fagan nomogram results showed a significant increase when correlating miR-141 with the diagnosis of prostate cancer. This meta-analysis suggests that miR-141 has a high diagnostic value for prostate cancer. In future, large-scale prospective studies will be done to verify and evaluate this result.     

Survival and clinical metastases among prostate cancer patients treated with androgen deprivation therapy in Sweden

ObjectivesTo examine the incidence of metastases and clinical course of prostate cancer patients who are without confirmed metastasis when initiating androgen deprivation therapy (ADT).MethodsRetrospective cohort study conducted using electronic medical records from Swedish outpatient urology clinics linked to national mandatory registries to capture medical and demographic data. Prostate cancer patients initiating ADT between 2000 and 2010 were followed from initiation of ADT to metastasis, death, and/or end of follow-up.ResultsThe 5-year cumulative incidence (CI) of metastasis was 18%. Survival was 60% after 5 years; results were similar for bone metastasis-free survival. The 5-year CI of castration-resistant prostate cancer (CRPC) was 50% and the median survival from CRPC development was 2.7 years. Serum prostate-specific antigen (PSA) levels and PSA doubling time were strong predictors of bone metastasis, any metastasis, and death.ConclusionThis study provides understanding of the clinical course of prostate cancer patients without confirmed metastasis treated with ADT in Sweden. Greater PSA values and shorter PSA doubling time (particularly ≤ 6 months) were associated with increased risk of bone metastasis, any metastasis, and death.     

Characterization of bone aluminum,a potential biomarker of cumulative exposure,within an occupational population from Zunyi,China

ObjectivesAluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs).MethodsWe completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al.ResultsMedian (interquartile range (IQR)) Al measurements were: 15 μg/g dry bone (IQR = 28) for bone Al; 34.9 μg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (β = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (β = 0.98, 95% CI: -0.14, 2.1; β = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant.ConclusionsBone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.     

A novel founder mutation in the RNASEL gene, 471delAAAG,is associated with prostate cancer in Ashkenazi Jews

HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population.     

Changes in prostate cancer at radical prostatectomy during the prostate specific antigen era: an Italian experience

OBJECTIVE: To assess changes in prostate cancer clinical and pathologic features by review of 15 years' experience with radical prostatectomy. STUDY DESIGN: A total of 596 consecutive patients who underwent open or laparoscopic radical prostatectomy (RP) between 1991 and 2006 were included. All had clinically localized prostate cancer. Surgical specimens were analyzed or blindly reviewed by a uropathologist, and whole-mount sections were prepared. Statistical analysis evaluated whether significant changes in clinical and pathologic variables occurred over time. RESULTS: Median prostate specific antigen (PSA) values at diagnosis significantly decreased over time. Definite stage migration was observed, with significant increase of organ-confined tumors. Incidence of seminal vesicle and lymph node involvement declined steadily. Median tumor volume decreased significantly over time (p<0.001). Incidence of nonsignificant cancers at RP increased significantly, reaching 25.6% in 2006. PSA value has progressively lost correlation with prostate cancer volume and today correlates only with prostate gland volume. CONCLUSION: Prostate cancer stage and volume at diagnosis have steadily decreased in the last 15 years, likely reflecting increasing use of PSA testing. In early prostate cancer, PSA level no longer correlates with tumor volume.     

A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese

An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.     

PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy

The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A>G at position-158) and CYP17 (substitution T>C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR=3.79, p=0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng=mL) compared with genotypes having at least one G allele (10.44 +/- 10.06 ng=mL) ( p=0.0687, 95% CI=0.3146 to 8.315, unpaired t-test). The multivariate analysis confirmed the association between PSA levels and PSA genotypes (AA vs. AG+ GG; chi2=0.0482) and CYP19 (short alleles homozygous vs. at least one long allele; chi2=0.0110) genotypes. Genetic instability at the AR locus leading to somatic mosaicism was detected in one PCa patient by comparing the length of AR CAG repeats in matched peripheral blood and prostate biopsy cores. Taken together, these findings suggest that the PSA genotype should be a clinically relevant biomarker to predict the PCa risk.     

Predictive Clinical Indicators of Biochemical Progression in Advanced Prostate Cancer Patients Receiving Leuplin Depot as Androgen Deprivation Therapy

Therapeutic planning and counseling for advanced prostate cancer patients receiving androgen deprivation therapy (ADT) is complicated because the prognoses are highly variable. The purpose of this study is to identify predictive clinical indicators of biochemical progression (BCP). In this retrospective analysis, data from 107 newly diagnosed patients (from November 1995 to April 2008) with advanced prostate adenocarcinoma receiving Leuprorelin acetate depot were analyzed. Data was collected from the computerized registry of two collaborating medical centers in Taiwan. Cox regression and Kaplan-Meier analyses were used to evaluate the relationship between potential predictive parameters and BCP. Univariate analysis revealed that predictors of BCP included (1) initial serum prostate-specific antigen (PSA) (hazard ratio [HR], 1.00; 95% confidence interval [CI] 1.00–1.00); (2) log of initial PSA (HR, 1.35; 95% CI 1.17–1.56); (3) PSA density at diagnosis (HR, 1.00; 95% CI 1.00–1.01), and (4) pathological bone fracture (HR, 2.22; 95% CI 1.20–4.11). Age (HR, 0.94; 95% CI 0.91–0.98) and hemoglobin levels (HR, 0.86; 95% CI 0.76–0.97) were also associated with greater risk of BCP. After adjusting for age, pathologic fracture, and hemoglobin level, the initial PSA and PSA density were no longer significantly associated with BCP. However, age and hemoglobin levels continued to be associated with greater risk of BCP (P≤0.007). Using Kaplan-Meier analysis, patients with higher initial PSA concentration, pathological bone fracture, and low hemoglobin had a greater probability of BCP. Thus, low hemoglobin and age are predictive indicators of BCP and therefore early indicators of BCP despite ADT therapy.     

Genetic polymorphisms of the interleukin-18 gene and risk of prostate cancer

Genetic factors are known to be important in the development of prostate cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL-18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to prostate cancer. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and -607 C/A polymorphisms and their haplotypes with the risk of prostate cancer. We analyzed two single nucleotide polymorphisms of IL-18 gene promoter -137 G/C and -607 C/A in 265 patients with prostate cancer and 280 age- and sex-matched controls, using sequence-specific primers-polymerase chain reaction strategy. There were significant differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of prostate cancer as compared with the -137 GG genotypes [odds ratio (OR) = 1.721; 95% confidence interval (CI): 1.187-2.496; p = 0.004, and OR = 2.181; 95% CI: 1.034-4.603; p = 0.037, for GC and CC, respectively]. Consistent with the results of the genotyping analyses, the -137C/-607A haplotype was associated with a significantly increased risk of prostate cancer as compared with the -137G/-607C haplotype (OR = 1.544; 95% CI, 1.137-2.096; p = 0.005). This study shows for the first time an association between IL-18 gene promoter -137 G/C polymorphism and prostate cancer in a Chinese population.     

Conformal radiotherapy (3D CRT) for non-metastatic androgen-independent prostate cancer: costly and sophisticated but ineffective treatment?

PurposePatients with diagnosis of hormone-refractory prostate cancers (HRPC) present a very heterogeneous population, and therefore it has been proposed to sub-categorize them into two subgroups depending on presence or absence of distant metastases. While the former subgroup has been typically treated with palliative intention, for the latter apparently there is no standard approach. The role of three-dimensional conformal radiotherapy (3D-CRT) for this subgroup has not been well documented in the literature. Thus, the purpose of this work is to analyze the results of treatment of non-metastatic androgen-refractory prostate cancer (ARPC) with 3D-CRT and to investigate the potential prognostic factors which influenced the results.Material and MethodsOf 424 patients with diagnosis of localized and locally advanced prostate cancer who were treated between 1999 and 2004 in our centre, forty-three (n=43) patients were classified as non-metastatic ARPC. Distant metastases were excluded by negative bone scan, negative chest X-ray and negative pelvic CT for lymph node metastases. The median pre-hormone therapy PSA (pre-HT PSA) level for this group was 24 ng/ml (range 1 to 120) and 5.7 ng/ml (range 0.06 to 27) at the beginning of radiotherapy (pre-RT PSA). Clinical T stage distribution, defined according to the 2002 AJCC, was as follows: T1c = 12, T2 = 23, and T3 = 8 patients, respectively. Of 44 patients, 39 had a Gleason score of 2-7 and 4 had a Gleason score of 8–10. All patients with diagnosis of non-metastatic ARPC were treated with 3D-CRT with the daily fraction dose of 2 Gy to a median total dose of 68 Gy (range from 60 to 74 Gy). The median duration of androgen ablation therapy before RT was 26 months (range from 7 to 96). The median time of follow-up after 3D-CRT was 27 months (range from 13 to 62) and from the beginning of androgen ablation was 53 months (range from 20 to 158). The following prognostic factors were evaluated in univariate and multivariate analysis: age, pre-HT PSA, pre-RT PSA, Gleason score, total dose, PSA doubling time (PSADT< 6 months vs. PSADT > 6 months).ResultsThe 5-year actuarial overall survival was 82% and 5-year clinical relapse free-survival rate was 49%. During the follow-up 14 patients developed disease progression (locoregional and/or distant and/or biochemical) and two patients died of prostate cancer. The univariate analysis indicated that pre-HT PSA > 20 ng/ml, pre-RT PSA > 4ng/ml, and the high-risk group defined according to NCCN criteria (PSA >20 ng/ml and Gleason score >7) were statistically significant factors for the risk of disease progression.ConclusionsThree-dimensional conformal radiotherapy for patients with non-metastatic ARPC is a valuable method of treatment for the subgroup of patients with pre-HT PSA<20 ng/ml and Gleason score < 8. For patients classified as the high-risk group according to NCCN criteria 3D-CRT seems to be an ineffective treatment due to the observed high incidence of distant failure, and should be viewed as costly and sophisticated yet ineffective intervention. For this subgroup a systemic modality of treatment such as chemotherapy or biological manipulation should be considered.     

Nuclear and cytoplasmic expression of ErbB-4 in prostate cancer

PURPOSE: To evaluate cytoplasmic and nuclear ErbB-4 expression in prostate cancer specimens and its association with outcome. BASIC PROCEDURES: Specimens of 50 prostate cancer patients were investigated for ErbB-4 overexpression using Immunohistochemistry staining. Cytoplasmic and nuclear staining was graded as 0-3 according to its intensity. The prognostic parameters were tumor stage, PSA level, Gleason score, probability of positive lymph nodes (Partin's tables and Roach equation), and 5-year disease free survival (Kattan nomogram). MAIN FINDINGS: Overexpression of ErbB-4 (> or = 1) was detected in 30 (60%) patients and overexpression using cytoplasmic and nuclear staining was > or = 2 in 19 (38%) and 17 (34%) patients, respectively. In only one third of the specimens was there any similarity between the 2 types of staining. Advanced tumor stage, high pretreatment PSA levels and high Gleason scores were evenly distributed among the patients with low (< or = 1) and intermediate/high (> or = 2) ErbB-4 expression. The probability of lymph node involvement and 5-year disease free survival were similar in both types of staining. PRINCIPAL CONCLUSIONS: ErbB-4 was overexpressed (cytoplasmic and nuclear staining) in approximately one third of prostate cancer patients. The rate of similarity between the 2 staining types was only 33%: overexpression was evenly distributed among intermediate/high and low risk prostate cancer patients with both staining methods.     

Long-term survival from adenocarcinoma of the esophagus after transthoracic and transhiatal esophagectomy

ABSTRACT: BACKGROUND: The effects of transthoracic or transhiatal esophagectomy on the long-term survival of patients who had adenocarcinoma of the esophagus were compared, as were factors applicable in preoperative stratification of patient treatment. METHODS: A cohort of 147 consecutive patients with adenocarcinoma of the esophagus was evaluated for esophagectomy between 1984 and 2000. The patients were followed prospectively and observed survival rates of patients with a transthoracic or transhiatal approach to esophagectomy were compared by standardized mortality ratio (SMR) and relative mortality ratio (RMR) using the expected survival of a matched Norwegian population. RESULTS: A R0 resection was performed by transthoracic (n = 33) or a transhiatal (n = 55) esophagectomy in 88 (60%) patients with a median age of 61 (range: 35-77) and 70 (42-88) years, respectively (P <0.001). Tumor stages and other possible risk factors were similar in the two groups. Transthoracic or transhiatal esophagectomy resulted in a median survival time of 20.5 (95% confidence interval (CI): 10.4-57.6) and 16.4 (10.6-28.7) months, respectively. The respective survival rates were 31.2% and 27.8% by 5 years, and 21.3% and 16.6% by 10 years with an overall RMR of 1.14 (P = 0.63). Median survival time in the absence or presence of lymph node metastases was 74.0 (95% CI: 17.5-166.4) and 10.7 (7.9- 14.9) months. The corresponding survival rates by 10 years with non-involved or involved nodes were 48.9% and 3.8% respectively (RMR 2.22, P = 0.007). Patients with a pT1-tumor were few and the survival rate was not very different from that of the general population (SMR = 1.7, 95% CI: 0.7-4.1). The median survival time of patients with a pT2-tumor was 30.4 (95% CI: 9.0-142) months and with a pT3-tumor 14 (9.2-16.4) months. The survival rates by 10 years among patients with a pT1 tumor were 57.0% (95% CI: 14.9-78.9), pT2 33.3% (11.8-52.2), and pT3 7.1% (1.9-15.5). The relative mortality for T3 stages compared to T1 stages was statistically significant (RMR = 3.22, P = 0.024). CONCLUSION: Transthoracic and transhiatal esophagectomy are both effective approaches for treatment of adenocarcinoma of the esophagus and survival of more than 10 years can be expected without adjuvant chemotherapy. However, increasing depth of tumor invasion and lymph node metastases reduce life expectancy.     

Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels

Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56?kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case?Ccontrol studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P?=?0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P?=?3.41?×?10^?4, per-allele trend odds ratio (OR)?=?0.77, 95% CI?=?0.67?C0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage <III (P?=?4.72?×?10^?5, per-allele trend OR?=?0.68, 95% CI?=?0.57?C0.82) and not for advanced cases with Gleason score >8 or stage ??III (P?=?0.31, per-allele trend OR?=?1.12, 95% CI?=?0.90?C1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61?ng/ml, 95% CI?=?1.49?C1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12?ng/ml, 95% CI?=?0.96?C1.28) (P?=?9.70?×?10^?5). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy.