Detection of prostate cancer using prostate-specific antigen adjusted for the transition zone volume in patients with intermediate serum prostate-specific antigen levels

Background. The prostate-specific antigen (PSA) density of the transition zone (PSATZ) in patients with PSA values of 4.1–10 ng/ml was determined to find whether PSATZ is useful in the detection of prostate cancer. Methods. The PSA, PSA density (PSAD), and PSATZ were determined in 101 patients with intermediate levels of serum PSA. The relationship of these parameters to prostate cancer detection was examined. Results. Patients with prostate cancer had significantly higher PSAD and PSATZ values than those without prostate cancer. In patients with a PSA value of 4.1–10 ng/ml, especially in those without abnormal digital rectal examination findings, PSATZ was superior to PSA as an indicator for positive biopsy when analyzed by receiver operating characteristics curves. In those patients with a cutoff value of 0.3 ng/ml per ml of transition zone volume, PSATZ had a sensitivity of 79% and a specificity of 51%. A cutoff value of 0.3 for PSATZ provided a sensitivity of 88% and a specificity of 51% in patients without abnormal digital rectal examination findings. Conclusion. The present study demonstrated that PSATZ was superior to PSA as an indicator for positive biopsy, especially in patients with normal digital rectal examination findings. PSATZ was not superior to PSAD in the detection of prostate cancer. Received: November 17, 1999 / Accepted: April 11, 2000     

Value of free-to-total prostate-specific antigen ratio for detection and staging of prostate cancer

Background. We aimed to evaluate the clinical usefulness of measurement of the free-to-total (F/T) ratio of prostate-specific antigen (PSA) for the differentiation of prostate cancer from benign prostate hyperplasia (BPH) and for the staging of prostate cancer. Values for PSA density (PSAD) and PSAD adjusted to the transition zone volume (PSAD-T) were also evaluated in patients with mildly elevated PSA levels (4.1–10 ng/ml). Methods. Total and free PSA and the F/T ratio were determined in 80 men with prostate cancer and 48 men BPH before treatment. PSA levels were measured with a chemiluminescent enzyme immunoassay. Results. Patients with prostate cancer had a significantly lower F/T ratio than those with BPH. A cut-off value of 14% for the F/T ratio provided a positive predictive value of 81.6% and a negative predictive value of 65.4%. The F/T ratio did not differ between patients with clinically localized and metastatic prostate cancer. In patients with a PSA value of 4.1–10 ng/ml, a cut-off value of 14% for the F/T ratio provided a sensitivity of 66.7% and a specificity of 76.2%. Sixty percent of the missed cancer in patients with an F/T value of 14% or more could be rescued using the PSAD value. Conclusion. Measurement of the F/T PSA ratio has good sensitivity and specificity in distinguishing prostate cancer from BPH, especially in patients with a PSA level of 4.1–10 ng/ml. However, compared with serum PSA level, the F/T PSA ratio is not valuable for the clinical staging of prostate cancer. Received: June 23, 1999 / Accepted: September 22, 1999     

前列腺特异性膜抗原在前列腺癌患者外周血和组织中的表达及意义

目的探讨前列腺特异性膜抗原（PSMA）在前列腺癌患者（PCa）外周血和组织中的表达及其与肿瘤病理分级和临床分期之间的关系。方法采用RT-PCR方法检测前列腺特异性膜抗原（PSMA）在前列腺癌和良性增生患者外周血清中的表达;采用免疫组化法观察PSMA在前列腺不同病变组织中的表达。前列腺癌28例,前列腺上皮内瘤（PIN）7例,良性前列腺增生（BPH）30例。结果血清学检测显示PSMA mRNA在前列腺癌和良性病变组（包括PIN和BPH）患者外周血中阳性率分别为67.9%和8.1%,两者差异具有显著性（P〈0.01）。在局限性癌、局部进展性癌和远处转移癌患者外周血肿瘤细胞中,PSMA mRNA的阳性率分别为58.3%、66.7%和85.7%,随前列腺癌临床分期的进展而逐渐递增（P〈0.05）。在高分化、中分化和低分化前列腺癌中,PSMA mRNA的阳性率分别为87.5%、62.5%和50%,肿瘤分化越差,其阳性率越低（P〈0.05）。组织学检测显示PSMA在PCa、PIN、BPH三种不同前列腺病变组织中的阳性率分别为60.7%、28.6%和20.0%（P〈0.05）,在高、中、低分化前列腺癌组织中PSMA的阳性率分别为100.0%、50.0%和25.0%,与肿瘤Gleason评分之间呈负相关（P〈0.05）。在局限性癌、局部进展性癌和远处转移癌患者肿瘤组织中,PSMA的阳性率分别为58.3%（7/12）、77.8%（7/9）和42.9%（3/7）（P〉0.05）。结论PSMA在前列腺癌组织中明显高表达,并且表达量与前列腺癌临床分期和分化程度（组织学分级）密切相关;检测PSMA可能对前列腺癌诊断、治疗方案的选择及预后评估具有重要价值。     

前列腺特异性抗原对中国人群前列腺癌早期检测价值的Meta分析

背景与目的：前列腺特异性抗原（prostate-specific antigen,PSA）是一种前列腺癌标志物,但关于使用PSA作为筛查标准是否合适仍存在争论。评价PSA在中国人群前列腺癌早期检测中的价值,旨在为前列腺癌筛查策略的制定提供依据。方法：对万方数据库、中国医院知识仓库（China Hospital Knowledge Database,CHKD）和PubMed数据库进行文献检索,再根据已发表文献中的参考文献追溯进行手工检索。收集2000年1月—2020年3月有关PSA对中国人群前列腺癌早期检测的文献资料。按确定的纳入标准筛选文献,对纳入的文献进行质量评价。对以PSA>4 ng/mL作为临界点检测前列腺癌的灵敏度、特异度等进行Meta分析。结果：共检索到5 722篇文献,排除重复及不符合标准的5 713篇后,纳入9篇文献。累计研究对象共6 425人,其中前列腺癌患者596例;Meta分析结果显示,以PSA>4 ng/mL作为临界点检测前列腺癌的灵敏度、特异度和集成受试者工作特征（summary receiver operating characteristic,SROC）曲线的曲线下面积（area under curve,AUC）分别为91%（95% CI：89%~93%）、41%（95% CI：27%~56%）和0.91（95% CI：0.88~0.93）。结论：中国人群中以PSA>4 ng/mL作为检测前列腺癌的界值,具有较高的灵敏度,但特异度较低,前列腺癌筛查可在PSA>4 ng/mL的基础上进一步筛选。     

66例局限期中危前列腺癌IMRT疗效分析

目的 分析局限期中危前列腺癌IMRT疗效和不良反应,分析PSA变化水平和意义。方法 回顾分析2007—2018年间经本院IMRT局限期中危前列腺癌66例资料。60例放疗前接受内分泌治疗,6例照射野包括盆腔淋巴引流区,47例采用IGRT技术。前列腺精囊腺中位剂量78 Gy,盆腔淋巴引流区中位剂量48 Gy。采用Kaplan-Meier法计算生存率。结果 中位年龄77岁,中位随访时间71.3个月。5年样本量47例。3、5年OS率分别为98%、90%,CSS率分别为100%、93%,BRFS率分别为97%、86%。PSA降至最低点的平均时间为5.83个月。IMRT后PSA最低点中位数为0.06 ng/ml。1、2级早期泌尿系统不良反应发生率分别为38%、6%,1、2级早期直肠不良反应发生率分别为21%、3%,1、2级晚期泌尿系统不良反应发生率分别为9%、2%,1级晚期直肠不良反应发生率为5%。结论 局限期中危前列腺癌IMRT疗效好,早期、晚期不良反应小,IMRT后PSA监测利于判断肿瘤预后。     

Predicting patient-specific response to adaptive therapy in metastatic castration-resistant prostate cancer using prostate-specific antigen dynamics

Abiraterone acetate (AA) has been proven effective for metastatic castration-resistant prostate cancer (mCRPC), and it has been proposed that adaptive AA may reduce toxicity and prolong time to progression, when compared to continuous AA. We developed a simple quantitative model of prostate-specific antigen (PSA) dynamics to evaluate prostate cancer (PCa) stem cell enrichment as a plausible driver of AA treatment resistance. The model incorporated PCa stem cells, non-stem PCa cells and PSA dynamics during adaptive therapy. A leave-one-out analysis was used to calibrate and validate the model against longitudinal PSA data from 16 mCRPC patients receiving adaptive AA in a pilot clinical study. Early PSA treatment response dynamics were used to predict patient response to subsequent treatment. We extended the model to incorporate metastatic burden and also investigated the survival benefit of adding concurrent chemotherapy for patients predicted to become resistant. Model simulations demonstrated PCa stem cell self-renewal as a plausible driver of resistance to adaptive therapy. Evolutionary dynamics from individual treatment cycles combined with metastatic burden measurements predicted patient response with 81% accuracy (specificity=92%, sensitivity=50%). In those patients predicted to progress, simulations of the addition of concurrent chemotherapy suggest a benefit between 1% and 11% reduction in probability of progression when compared to adaptive AA alone. This study developed the first mCRPC patient-specific mathematical model to use early PSA treatment response dynamics to predict subsequent responses to adaptive AA, demonstrating the putative value of integrating mathematical modeling into clinical decision making.     

Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study

Objective To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer. Methods In 1989, 3,892 men 35+ years old, who participated in the CLUE II study of Washington County, MD, completed an abbreviated Block food frequency questionnaire. Intake of meat and dairy foods was calculated using consumption frequency and portion size. Incident prostate cancer cases (n = 199) were ascertained through October 2004. Cox proportional hazards regression was used to calculate hazard ratios (HR) of total and advanced (SEER stages three and four; n = 54) prostate cancer and 95% confidence intervals (CI) adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato products. Results Intakes of total meat (HR = 0.90, 95% CI 0.60–1.33, comparing highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59–1.32) were not statistically significantly associated with prostate cancer. However, processed meat consumption was associated with a non-statistically significant higher risk of total (5+ vs. ≤1 servings/week: HR = 1.53, 95% CI 0.98–2.39) and advanced (HR = 2.24; 95% CI 0.90–5.59) prostate cancer. There was no association across tertiles of dairy or calcium with total prostate cancer, although compared to ≤1 serving/week consumption of 5+ servings/week of dairy foods was associated with an increased risk of prostate cancer (HR = 1.65, 95% CI 1.02–2.66). Conclusion Overall, consumption of processed meat, but not total meat or red meat, was associated with a possible increased risk of total prostate cancer in this prospective study. Higher intake of dairy foods but not calcium was positively associated with prostate cancer. Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested.     

Detection of prostate-specific antigen coupled to immunoglobulin M in prostate cancer patients

Background: Several reports indicate that the main biomarkers for liver and colorectal cancer circulating in the blood stream associate with immunoglobulin M (IgM) to form stable complexes that show increased diagnostic relevance compared to circulating free biomarkers. Methods: To further investigate the association between cancer biomarkers and IgM, we assessed the presence of prostate-specific antigen (PSA) as IgM complexes in sera of patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH) in comparison with PSA measurements. Results: PSA–IgM levels were significantly elevated in 40% (20/50) and 12% (6/51) of PC and BPH patients, respectively, compared to 22% (11/50) and 29% (15/51) of PSA positive patients in the same groups. Detection of cancer markedly increased from 22 to 60% by co-determination of both markers (30/50 patients). Significantly elevated levels of PSA–IgM were found in 13 out of 30 patients affected by PC with a PSA value between 4 and 10 ng/mL and only in 4 out of 34 BPH patients in the same PSA range. Conclusions: The results are the first evidence of the occurrence of PSA–IgM complexes in patients with prostate cancer. The gain achieved in cancer detection by using the combination of PSA and PSA–IgM suggests that PSA–IgM could be a complementary serological marker of prostate cancer.     

Intake of whole-grain products and risk of prostate cancer among men in the Danish Diet,Cancer and Health cohort study

Objective  

High intake of whole-grain products may protect against prostate cancer, but overall evidence is limited and inconclusive. The aim of the present study was to investigate the relationship between the intake of whole-grain products and risk of prostate cancer in a large prospective cohort.     

History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP Diet and Health Study

Objective A history of diabetes has been hypothesized to decrease prostate cancer risk, but studies have not always considered confounding or effect modification by dietary or lifestyle factors. Methods We examined the association between diabetes history and subsequent prostate cancer risk in 328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were ages 50–71 years and without a prostate cancer diagnosis at baseline in 1995. A prior history of physician-diagnosed diabetes was assessed using a self-administered mailed questionnaire. Cases of prostate cancer were ascertained by matching the cohort to state cancer registries. Multivariable relative risks (RR) and 95% confidence intervals (CI) of prostate cancer were estimated using Cox regression. Results During 5 years and 1,432,676 person-years of follow-up, 11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable RRs of prostate cancer comparing men with diabetes to those without diabetes were 0.69 (95% CI = 0.64, 0.74) and 0.71 (95% CI = 0.66, 0.76), respectively, indicating no important confounding. The inverse association between diabetes and prostate cancer was particularly strong among men in the highest category of routine physical activity at work or home (RR = 0.41; 95% CI = 0.23, 0.74; p value for test of interaction = 0.03). Findings were similar for organ-confined and advanced prostate cancer. Conclusion Results from this large prospective study suggest that a history of diabetes is associated with a decreased risk of prostate cancer. The relationship strengthened with high levels of routine physical activity. Because increased physical activity is associated with lower circulating levels of insulin and testosterone, our findings support a role of hypoinsulinemia and low androgenicity linking diabetes to decreased prostate cancer risk.     

Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in Japanese

A recent whole‐genome association study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer risk. In this case‐control study, we aimed to validate this association, and further to explore environmental factors possibly interacting with PSCA polymorphisms in 708 incident stomach cancer cases and 708 age–sex matched controls. The association between PSCA polymorphisms and Helicobacter pylori infection was also examined. We found that rs2294008 and rs2976392, which were strongly linked to each other (D′ = 1.00), were significantly associated with stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence interval: 1.19–1.65; p = 3.7 × 10^?5). We found significant interaction with a family history of stomach cancer in first‐degree relatives (p‐heterogeneity = 0.009). Similar to originally reported association, we found significant heterogeneity between diffuse and intestinal type (p‐heterogeneity = 0.007). No association was seen between PSCA polymorphisms and H. pylori infection. In conclusion, PSCA polymorphisms are associated with stomach cancer risk in Japanese. A possible interaction with family history warrants further evaluation. © 2009 UICC     

Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Objective  A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. Methods  We prospectively examined the diabetes–prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results  During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68–0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62–0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum ≥8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74–1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87–3.07; BMI < 25 kg/m²) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07–2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively). Conclusion  In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.     

Prostate cancer mortality in relation to screening by prostate-specific antigen testing and digital rectal examination: a population-based study in middle-aged men

Background Although prostate cancer screening by measurement of serum prostate-specific antigen (PSA) and digital rectal examination (DRE) is common in clinical practice, the impact of such screening on prostate cancer-specific mortality remains uncertain. Methods Data from a population-based case–control study in King County, Washington, among men aged 50–64 years (706 cases, 645 controls) were used to examine the relationships between PSA and DRE screening and fatal prostate cancer and other-cause mortality. Incident cases were diagnosed in 1993–1996, identified via the Seattle-Puget Sound SEER cancer registry and followed for vital status through 1 June 2007. Controls were ascertained by random digit dialing and frequency age-matched to cases. The screening variable used in this analysis was self-reported receipt of one or more PSA and/or DRE tests performed as part of a routine checkup in the five-year period before diagnosis or reference date. Results A smaller proportion of men with fatal prostate cancer had one or more PSA and/or DRE screening tests compared to controls, resulting in an adjusted odds ratios (OR) of 0.38 (95% CI 0.19–0.77). There was no association, however, between PSA and/or DRE screening and other-cause mortality (OR = 1.02; 95% CI 0.51–2.02). Conclusions Results of this study suggest a reduction in prostate cancer-specific mortality associated with PSA and/or DRE screening in middle-aged men. Findings should be interpreted cautiously, however, as results are based on observational data. Further, the study was not able to separate the relative efficacy of PSA versus DRE screening.     

Test sensitivity of prostate-specific antigen in the Finnish randomised prostate cancer screening trial

We estimated the sensitivity of serum prostate-specific antigen (PSA) as a screening test for prostate cancer in the Finnish randomised, population-based prostate cancer screening trial. The study population consisted of 80,458 men aged 55-67 years identified from the national population registry and randomised to the screening or control arm of the trial. The screening algorithm was based on determination of serum PSA concentration. Test sensitivity was estimated based on interval cancer incidence during the first 4 years of follow-up among screening participants with a negative screening test. Interval cancers were defined as those occurring among men with a negative screening test. Altogether, 19 interval cancers were detected among 17,897 men with serum PSA < 3 ng/ml during the first screening interval. A further 5 cases were diagnosed among 811 men with PSA 3.0-3.9 ng/ml with a benign digital rectal examination or free total PSA ratio > or = 0.16. Test sensitivity based on serum PSA of 3 ng/ml was estimated to be 0.89 (95% confidence interval 0.84-0.93) and that based on PSA of 4 ng/ml combined with an ancillary test (digital rectal examination or free total PSA ratio in the PSA range 3.0-3.9) was 0.87 (0.82-0.92). Test sensitivity achieved with serum PSA in prostate cancer screening appears excellent in the context of a population-based effectiveness trial.     

Food groups and risk of prostate cancer in Italy

Although several studies have been conducted, the relation between diet and prostate cancer remains unclear. The role of a wide range of foods on the risk of prostate cancer has thus been analyzed in a case-control study conducted in Italy between 1991 and 2002. Cases were 1,294 patients below age 75 years with incident, histologically confirmed carcinoma of the prostate; controls were 1,451 subjects below age 75 years admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for major potential confounding factors, including calorie intake. Among the 19 food groups considered, 4 showed some significant association with prostate cancer risk. A significant trend of increasing risk with more frequent consumption was found for milk and dairy products (OR = 1.2 for highest vs. lowest quintile, p = 0.03) as well as bread (OR = 1.4, p = 0.01), whereas inverse associations were observed for soups (OR = 0.8, p = 0.02) and cooked vegetables (OR = 0.7, p = 0.01). This uniquely large study on prostate cancer and diet in a southern European population confirms that no strong association exists between any specific foods and prostate cancer, apart from an increased risk for milk and dairy products and a possible protective effect of vegetables.     

广东地区前列腺癌发病与家族史和婚育史关系的病例对照研究

背景与目的:前列腺癌(prostate cancer)是欧美发达国家老年男性的常见恶性肿瘤之一,中国前列腺癌的发病率较低,但逐年上升.国内前列腺癌的病因学研究主要集中于上海、武汉和北京等地区,而来自广东地区的报道较少.本研究旨在探讨广东地区前列腺癌与家族史和婚育史的病因学关联.方法:在中山大学4所附属医院开展一项病例对照研究(1:2配对),匹配条件为年龄组(±5岁)、性别、民族和居住地类型相同.调查以面谈为主,辅以调查病历记录,采用条件Logistic回归法分析数据.结果:本次调查共获得有效资料186份,其中前列腺癌患者62例,良性前列腺增生的患者62例和其他疾病对照62例.以前列腺增生为对照,遗精年龄小于15岁者患前列腺癌的危险是18岁以上者的6.37倍(95%CI=0.63～63.95);与30岁以上首次进行性生活者相比,首次性生活年龄小者患前列腺癌的危险增高,20～24岁组OR=2.25(95%CI=0.75～6.71),25～29岁组OR=2.34(95%CI=0.89～6.13);60岁以后失去性生活者是前列腺癌的保护因素,60～69岁OR=0.51(95%CI=0.20～1.27),70岁及以上组OR=0.31(95%CI=0.08～1.24).以其它疾病为对照,有一个一级亲属患恶性肿瘤者患前列腺癌的危险是无恶性肿瘤家族史的2.25倍(95%CI=0.69～7.31);首次性生活年龄小于20岁者患前列腺癌的危险是30岁及以上者的5.07倍(95%CI=0.50～51.46);而60岁以后失去性生活者是前列腺癌发生的保护因素,60～69岁组OR=0.55(95%CI=0.24～1.26),70岁及以上组OR=0.41(0.11～1.47).结论:首次遗精年龄和首次性生活年龄较早均为前列腺癌的危险因素,有恶性肿瘤家族史者患前列腺癌的危险增加.     

The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk

The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age < or =65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45-69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were > or =4 ng ml(-1) and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied.     

Optimizing patient selection for dose escalation techniques using the prostate-specific antigen level, biopsy gleason score, and clinical T-stage

Purpose: Ideal candidates for 3D dose escalation conformal radiation or external beam + implant therapy are identified on the basis of the prostate-specific antigen (PSA) level, biopsy Gleason score, and the 1992 American Joint Commission Cancer (AJCC) clinical T-stage.

Methods and Materials: The pathologic findings of 1742 men with clinical stage T1c,2 prostate cancer managed with a radical prostatectomy (RP) between 1990 and 1998 were subjected to a logistic regression multivariable analysis. The endpoints examined included pathologic organ–confined (OC), specimen-confined (SC), and margin (M) or seminal vesicle (SV) positive disease. SC disease was defined as extracapsular extension (ECE) with a negative surgical margin. The clinical factors tested included PSA level, biopsy Gleason score, and the 1992 AJCC clinical T-stage. PSA failure–free (bNED) survival was calculated according to the method of Kaplan and Meier.

Results: Significant negative predictors of pathologic OC–disease or positive predictors of M⁺ or SV⁺ disease included a PSA > 10 ng/ml (p < 0.0001), biopsy Gleason score ≥7 (p ≤ 0.0004), and ≥ T2b disease (p ≤ 0.03). Only biopsy Gleason score 7 (p = 0.0006) and PSA 10–15 ng/ml (p = 0.04) were significant predictors of SC disease. The estimates of 5-year bNED survival were 80%, 62%, and 35% (p < 0.0001) for patients having a low, intermediate, or high likelihood of having M⁺ or SV⁺ disease respectively.

Conclusions: Patients most likely to derive a survival benefit from the improved local control possible using dose escalation techniques were those who had both a low risk of having occult micrometastatic disease (<25% M⁺ or SV⁺) and a reasonable likelihood of remaining disease-free after RP (>50% 5-year bNED). These patients included those having T1c, 2a, PSA > 10–15 ng/ml, and biopsy Gleason ≤6 or T1c, 2a, 2b, PSA ≤ 10 ng/ml, and biopsy Gleason ≤ 7 prostate cancer.     

Cigarette smoking and mammographic density in the Danish Diet,Cancer and Health cohort

Purpose

Smoking before first childbirth increases breast cancer risk, but the biological mechanism remains unknown and may involve mammographic density (MD), one of the strongest biomarkers of breast cancer risk. We aimed to examine whether active smoking and passive smoking were associated with MD.

Methods

For the 5,356 women (4,489 postmenopausal) from the Danish Diet, Cancer and Health cohort (1993–1997) who attended mammographic screening in Copenhagen (1993–2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Active smoking (status, duration, and intensity) and passive smoking were assessed at cohort baseline (1993–1997) via questionnaire, together with other breast cancer risk factors. Logistic regression was used to estimate associations (odds ratios, 95 % confidence intervals) between smoking and MD, adjusting for confounders.

Results

Two thousand and twenty-six (56.5 %) women had mixed/dense MD, 2,214 (41.4 %) were current, and 1,175 (21.9 %) former smokers. Current smokers had significantly lower odds (0.86, 0.75–0.99) of having mixed/dense MD compared to never smokers, while former smoking was not associated with MD. Inverse association between smoking and MD was strongest in women who initiated smoking before age of 16 years (0.79, 0.64–0.96), smoked ≥15 cigarettes/day (0.83, 0.71–0.98), smoked ≥5 pack-years (0.62, 0.43–0.89), smoked >30 years (0.86, 0.75–0.99), and smoked ≥11 years before first childbirth (0.70, 0.51–0.96). Association between smoking and MD diminished after smoking cessation, with increased odds of having mixed/dense breasts in women who quit smoking >20 years ago as compared to current smokers (1.37, 1.01–1.67). There was no association between passive smoking and MD.

Conclusions

We found an inverse association between active smoking and MD.