Body mass index in relation to serum prostate‐specific antigen levels and prostate cancer risk

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate‐specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010–2012. During follow‐up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high‐grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log‐PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer‐free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: ?2.1 to ?1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI‐categories of 25 < 30, 30 < 35 and ≥35 kg/m², respectively, compared to the reference (18.5 < 25 kg/m²). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high‐grade disease and an inverse association to incidence of low‐grade disease. However, findings regarding risk are limited by the short follow‐up time. In conclusion, BMI was inversely associated to PSA‐levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA‐levels.     

Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality

BACKGROUND: For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA) recurrence, whether the time to an undetectable (u) PSA was significantly associated with prostate cancer-specific mortality (PCSM) was evaluated. METHODS: The study cohort comprised 585 men with a rising PSA and negative bone scan after surgery (n = 415) or radiation therapy (n = 170) that were treated with AST and achieved a uPSA. Gray's regression was used to evaluate whether the time to a uPSA after AST was significantly associated with the time to PCSM after the uPSA adjusting for known prognostic factors. RESULTS: The median time (interquartile range) to achieve a uPSA was 4.6 (range, 2.8-7.8) months. There were 23 deaths, 4 of which were from prostate cancer. An increasing time to a uPSA (adjusted hazard ratio [HR]: 9.2, 95% confidence interval [CI]: 3.8, 22.1; P < .0001), a decreasing PSA doubling time (DT) (HR: 0.58, 95% CI: 0.43, 0.80; P = .0007), and Gleason score 8 to 10 cancers (HR: 8.6, 95% CI: 1.04, 77; P = .05) were significantly associated with a shorter time to PCSM. CONCLUSIONS: Despite achieving a uPSA after AST, the risk of PCSM increased significantly as the time to the uPSA lengthens, especially in men with a short pre-AST PSA DT and high-grade prostate cancer. These men should be considered for randomized studies evaluating immediate vs delayed chemotherapy after the achievement of the uPSA.     

Relationship of prediagnostic body mass index with survival after colorectal cancer: Stage‐specific associations

Higher body mass index (BMI) is a well‐established risk factor for colorectal cancer (CRC), but is inconsistently associated with CRC survival. In 6 prospective studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), 2,249 non‐Hispanic white CRC cases were followed for a median 4.5 years after diagnosis, during which 777 died, 554 from CRC‐related causes. Associations between prediagnosis BMI and survival (overall and CRC‐specific) were evaluated using Cox regression models adjusted for age at diagnosis, sex, study and smoking status (current/former/never). The association between BMI category and CRC survival varied by cancer stage at diagnosis (I‐IV) for both all‐cause (p‐interaction = 0.03) and CRC‐specific mortality (p‐interaction = 0.04). Compared to normal BMI (18.5–24.9 kg/m²), overweight (BMI 25.0–29.9) was associated with increased mortality among those with Stage I disease, and decreased mortality among those with Stages II–IV disease. Similarly, obesity (BMI ≥30) was associated with increased mortality among those with Stages I–II disease, and decreased mortality among those with Stages III–IV disease. These results suggest the relationship between BMI and survival after CRC diagnosis differs by stage at diagnosis, and may emphasize the importance of adequate metabolic reserves for colorectal cancer survival in patients with late‐stage disease.     

Prostate cancer‐specific mortality and the extent of therapy in healthy elderly men with high‐risk prostate cancer

BACKGROUND:

The risk of prostate cancer‐specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external‐beam radiation to the prostate and seminal vesicles, and androgen‐suppression therapy (CMT) in this population.

METHODS:

The study cohort comprised 764 men aged ≥65 years with high‐risk prostate cancer (T3 or T4N0M0, prostate‐specific antigen >20 ng/mL, and/or Gleason score 8‐10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM.

RESULTS:

The median patient age was 73 years (interquartile range, 70‐77 years). After a median follow‐up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12‐0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017).

CONCLUSIONS:

Elderly men who had high‐risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high‐risk prostate cancer. Cancer 2010. © 2010 American Cancer Society.     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

Effect of comorbidity and body mass index on the survival of African‐American and Caucasian patients with colon cancer

BACKGROUND:

There is a survival disparity between African Americans and Caucasians who have colon cancer. The objectives of the current study were to quantify the impact of comorbidity and body mass index (BMI) on survival and to assess whether these 2 variables account for the decreased survival among African Americans.

METHODS:

Data from patients (n = 496) who underwent surgery for a first primary colon cancer at the University of Alabama at Birmingham Hospital from 1981 to 2002 were analyzed. Hazard ratios (HRs) with 95% confidence intervals (CI) were obtained using Cox proportional hazards models for the association of race, comorbidity, BMI, and covariates with all‐cause mortality. The confounding influence of comorbidity and BMI for the increased risk of death associated with African‐American race was evaluated, and effect modification by disease stage for the association of comorbidity and BMI with mortality also was assessed.

RESULTS:

African Americans experienced an increased risk of death compared with Caucasians (HR, 1.34; 95% CI, 1.06‐1.68). The highest comorbidity burden was associated with an increased risk of all‐cause mortality (HR, 1.63; 95% CI, 1.24‐2.15). For BMI, being underweight increased the risk of death (HR, 1.54; 95% CI, 0.96‐2.45); however, being overweight/obese was protective (HR, 0.77; 95% CI, 0.61‐0.97). The effect of comorbidity was observed among those with early stage tumors, whereas the effect of BMI was confined to patients who had advanced tumors.

CONCLUSIONS:

Although comorbidity and BMI had an impact on the survival of patients with colon cancer after surgery, these variables were not contributing factors to the decreased survival observed among African Americans. Cancer 2009. © 2009 American Cancer Society.     

Association of body mass index and height with risk of prostate cancer among middle-aged Japanese men

In a population-based prospective study of 49 850 Japanese men, body mass index and height were not significantly associated with risk of prostate cancer (311 cases), although small positive effects could not be ruled out in advanced cases (91 cases).     

Time to prostate‐specific antigen nadir independently predicts overall survival in patients who have metastatic hormone‐sensitive prostate cancer treated with androgen‐deprivation therapy

BACKGROUND:

The objective of this study was to evaluate the relation between the kinetics of prostate‐specific antigen (PSA) decline after the initiation of androgen‐deprivation therapy (ADT) and overall survival (OS) in men with metastatic, hormone‐sensitive prostate cancer (HSPC).

METHODS:

The authors' institutional database was used to identify a cohort of men with metastatic HSPC who were treated with ADT. Patients were included if they had at least 2 serum PSA determinations before PSA nadir and at least 1 serum PSA value available within 1 month of ADT initiation. Patient characteristics, PSA at ADT initiation, nadir PSA, time to PSA nadir (TTN), and PSA decline (PSAD) in relation to OS were analyzed.

RESULTS:

One hundred seventy‐nine patients were identified, and they had a median follow‐up after ADT initiation of 4 years. The median OS after ADT initiation was 7 years. The median PSA level at ADT initiation and PSA nadir were 47 ng/mL and 0.28 ng/mL, respectively. On univariate analysis: TTN <6 months, PSAD >52 ng/mL per year, PSA nadir ≥0.2 ng/mL, PSA ≥47.2 ng/mL at ADT initiation, and Gleason score >7 were associated with shorter OS. On multivariate analysis, TTN <6 months, Gleason score >7, and PSA nadir ≥0.2 ng/mL independently predicted shorter OS.

CONCLUSIONS:

To the authors' knowledge, this was the first report to demonstrate that a faster time to reach a PSA nadir after the initiation of ADT was associated with shorter survival duration in men with metastatic HSPC. These results need confirmation but may indicate that a rapid initial response to ADT indicates more aggressive disease. Cancer 2009. © 2009 American Cancer Society.     

Quantitative association between body mass index and the risk of cancer: A global Meta‐analysis of prospective cohort studies

Numerous studies have suggested that excess body weight is associated with increased cancer risk. To examine this putative association, we performed a systematic review and quantitative meta‐analysis of cohort studies reporting body mass index (BMI) and the risk of 23 cancer types. PubMed, Embase, and Web of Science were searched for cohort studies, yielding 325 articles with 1,525,052 cases. Strong positive associations were observed between BMI and endometrial cancer (RR: 1.48), esophageal adenocarcinoma (RR: 1.45), and kidney cancer (RR: 1.20); weaker associations (RR < 1.20) were also found for several other cancer types. Interestingly, we found significant inverse associations between BMI and oral cavity (RR: 0.93), lung (RR: 0.91), premenopausal breast (RR: 0.95), and localized prostate (RR: 0.97) cancers. A male‐specific association was found for colorectal cancer (p = 0.023), and a female‐specific association was found for cancer in brain (p = 0.025) or kidney (p = 0.035). With respect to geography, the strongest positive association was found for total cancer in North America (p = 0.038). This comprehensive meta‐analysis provides epidemiological evidence supporting the association between BMI and cancer risk. These findings can be used to drive public policies and to help guide personalized medicine in order to better manage body weight, thereby reducing the risk of developing obesity‐related cancer.     

Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature

Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA < 10 ng/mL, Gleason score < or =6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores > or =7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy.     

Clinical significance of the LacdiNAc‐glycosylated prostate‐specific antigen assay for prostate cancer detection

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc‐glycosylated prostate‐specific antigen (LDN‐PSA) and LDN‐PSA normalized by prostate volume (LDN‐PSAD). We retrospectively measured LDN‐PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop‐PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN‐PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN‐PSA and LDN‐PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop‐PSA cohort, LDN‐PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc‐glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution (“The Study about Carbohydrate Structure Change in Urological Disease”; approval no. 2014‐195).     

Body mass index,height, and postmenopausal breast cancer mortality in a prospective cohort of US women

Objective: Epidemiologic evidence suggests a positive association between body mass, adult height, and postmenopausal breast cancer. However, most studies have not been large enough to examine the association across a very wide range of body mass or height, and few studies have assessed the relationship between body mass or height and postmenopausal breast cancer mortality. Methods: The relation between body mass index (BMI) and height and postmenopausal breast cancer mortality was examined in the American Cancer Society's Cancer Prevention Study II (CPS-II), a large prospective mortality study of US adults enrolled in 1982. After 14 years of follow-up, 2852 breast cancer deaths were observed among 424,168 postmenopausal women who were cancer-free at interview. Cox proportional hazards modeling was used to estimate relative risks and to control for potential confounding. Results: Breast cancer mortality rates increased continually and substantially with increasing BMI (rate ratio (RR) = 3.08, 95% confidence interval (CI) = 2.09–4.51 for BMI 40.0 compared to BMI 18.5–20.49). If causal, the multivariate-adjusted RR estimates in this study correspond to approximately 30–50% of breast cancer deaths among postmenopausal women in the US population being attributable to overweight. Breast cancer mortality also increased with increasing height up to 66 inches with RR = 1.64, (95% CI = 1.23–2.18) in women 66 inches tall compared to those < 60 inches. Conclusions: Postmenopausal obesity is an important and potentially avoidable predictor of fatal breast cancer in this study. These results underscore the importance of maintaining moderate weight throughout adult life.     

Infectious mononucleosis,other infections and prostate‐specific antigen concentration as a marker of prostate involvement during infection

Although Epstein‐Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult‐onset IM on the prostate by measuring prostate‐specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.     

Low body mass index is an independent predictive factor of local recurrence after conservative treatment for breast cancer

Background. Obesity or increased body mass index (BMI) has been shown to have two important adverse effects related to breast cancer. First, several studies have identified an association between increased BMI and advanced stage breast cancer. Second, increased BMI has been shown to be associated with poorer prognosis. In a previous report, we had identified low BMI as a risk factor for local reccurence at five years. The objectives of this study were to evaluate the relationship between BMI and local control and to confirm this prognostic factor in a larger population with an important follow-up. Materials and methods. Between 1976 and 1988, 605 women with invasive breast carcinoma less than 4cm in diameter underwent conservative surgery with axillary dissection and radiation therapy. The median follow-up time was 82 months. The risk of local recurrence and distant metastasis was evaluated by univariate retrospective analysis using Kaplan–Meier method for the main clinical and histologic factors. Those found to be significant were entered in a Cox model for multivariate analysis. Results. Since the beginning of the study, 80 patients had developed local recurrence. The 5 years and 10 years local control rates were 91% and 83%, respectively. Four parameters were independent predictive factors of local recurrence: Age lower than 40 years (HR=2.42 95% CI=[1.35–4.34]), BMI: elevation of one unit reducing the local recurrence of 0.92 95%CI=[0.85–0.99], multifocality of the tumor on pathological examination (HR=2.12 95% CI=[1.16–3.88]) and positive axillary nodes HR=0.54 95% CI=[0.31–0.95]. Size of the breast was not a predictive factor for local cancer recurrence. Low BMI did not increase risk of distant. Conclusion. Our study offers new data concerning the possibility that thinness may be related to local recurrence of breast cancer.