2005 Cancer in Iowa Report: Prostate Cancer in Iowa, 2005

Cancer is a reportable disease as stated in the Iowa Administrative Code. Cancer data are collected by the State Health Registry of Iowa, located at The University of Iowa in the College of Public Health’s Department of Epidemiology. The staff includes more than 50 people. Half of them, situated throughout the state, regularly visit hospitals, clinics, and medical laboratories in Iowa and neighboring states to collect cancer data. A follow-up program tracks more than 97 percent of the cancer survivors diagnosed since 1973. This program provides regular updates for follow-up and survival. The Registry maintains the confidentiality of the patients, physicians, and hospitals providing data. In 2005 data will be collected on an estimated 15,800 new cancers among Iowa residents. Beginning with 2005 Cancer in Iowa, in situ cases of bladder cancer are included in the estimates for bladder cancer, to be in agreement with the definition of reportable cases of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. Since 1973 the Iowa Registry has been funded by the SEER Program of the National Cancer Institute. Iowa represents rural and midwestern populations and provides data included in many NCI publications. Beginning in 1990 about 5-10 percent of the Registry’s annual operating budget has been provided by the state of Iowa. Beginning in 2003, the University of Iowa has also been providing cost-sharing funds. The Registry also receives funding through grants and contracts with university, state, and national researchers investigating cancer-related topics.

Acute toxicity of curative radiotherapy for intermediate- and high-risk localised prostate cancer in the EORTC trial 22991.

INTRODUCTION: This trial randomly assessed short-term adjuvant hormonal therapy added to radiotherapy (RT) for intermediate- and high-risk (UICC 1997 cT2a or cT1b-c with high PSA or Gleason score) localised prostate cancer. We report acute toxicity (CTCAE v2) assessed weekly during RT in relation to radiation parameters. PATIENTS AND METHODS: Centres selected the RT dose (70, 74 or 78Gy) and RT technique. Statistical significance is at 0.05. RESULTS: Of 791 patients, 652 received 3D-CRT (70Gy: 195, 74Gy: 376, 78Gy: 81) and 139 received IMRT (74Gy: 28, 78Gy: 111). During RT, grade 3 gastrointestinal (GI) and genitourinary (GU) toxicities were reported by 7 (0.8%) and 50 (6.3%) patients, respectively. No grade 4 was reported. The risk of grade 2 GI toxicity increased significantly with increasing D50%-rectum (p=0.004) and that of grade 2 GU toxicity correlated only to Dmax-bladder (p=0.051). 3D-RT technique, increasing total dose and V95% >400 cc increased D50% and Dmax. One month after RT, only 14 patients (1.8%) reported grade 3 toxicity. AST did not seem to influence the risk of GU or GI acute toxicity. CONCLUSION: RT up to 78Gy was well tolerated. Dmax-bladder and D50%-rectum influenced the risk of grade 2 GU toxicity and GI toxicity, respectively. Both were lower with IMRT but remained high for an irradiated RT volume>400 cc for 3D-RT and for a dose of 78Gy. Hormonal treatment did not influence acute toxicity.

Can 3T multiparametric magnetic resonance imaging accurately detect prostate cancer extracapsular extension?

BACKGROUND: Accurate staging is essential to determine the correct management of patients diagnosed with prostate cancer. We assess the accuracy of 3T multiparametric magnetic resonance imaging (MRI) with endorectal coil (3TemMRI) in detecting prostate cancer local extension. METHODS: We retrospectively reviewed charts from January 2008 to July 2012 from all patients undergoing radical prostatectomy. Patients were only included if 3TemMRI and radical prostatectomy were performed at our institution. Based on the presence of extracapsular extension (ECE) at 3TemMRI, prostate cancer was dichotomized into locally advanced or organ-confined disease. The accuracy of 3TemMRI local staging was then evaluated using definitive pathology as a reference. RESULTS: Overall, 177 radical prostatectomies were performed within the timeframe. After applying exclusion criteria, 60 patients were included in the final analysis. The mean patient age was 67 ± 7 (standard deviation) years. Mean prostate-specific antigen value was 12.7 ± 12.7 ng/L. Based on preoperative characteristics, we considered 38 of the 60 patients (63%) patients high risk. 3TemMRI identified an organ-confined tumour in 46 patients and locally advanced disease in 14 patients. When correlated to final pathology, 3TemMRI specificity, sensitivity, negative and positive predictive values, and accuracy in detecting locally advanced prostate cancer were 90%, 35%, 57%, 79% and 62%, respectively. INTERPRETATION: This study shows that the use of preoperative 3TemMRI can be used to identify organ-confined prostate cancer when locally advanced disease is suspected.

Family history of cancer and the risk of cancer: a network of case-control studies.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. CONCLUSIONS: Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.

European cancer mortality predictions for the year 2012.

BACKGROUND: Estimating current cancer mortality figures is important for defining priorities for prevention and treatment.Materials and methods:Using logarithmic Poisson count data joinpoint models on mortality and population data from the World Health Organization database, we estimated numbers of deaths and age-standardized rates in 2012 from all cancers and selected cancer sites for the whole European Union (EU) and its six more populated countries. RESULTS: Cancer deaths in the EU in 2012 are estimated to be 1 283 101 (717 398 men and 565 703 women) corresponding to standardized overall cancer death rates of 139/100 000 men and 85/100 000 women. The fall from 2007 was 10% in men and 7% in women. In men, declines are predicted for stomach (-20%), leukemias (-11%), lung and prostate (-10%) and colorectal (-7%) cancers, and for stomach (-23%), leukemias (-12%), uterus and colorectum (-11%) and breast (-9%) in women. Almost stable rates are expected for pancreatic cancer (+2-3%) and increases for female lung cancer (+7%). Younger women show the greatest falls in breast cancer mortality rates in the EU (-17%), and declines are expected in all individual countries, except Poland. CONCLUSION: Apart for lung cancer in women and pancreatic cancer, continuing falls are expected in mortality from major cancers in the EU.

Applications de la chirurgie robotique transorale dans les tumeurs de la sphère ORL [The role of transoral robotic surgery in head and neck cancer].

Since 2000 and the commercialisation of the Da Vinci robotic system, indications for robotic surgery are rapidly increasing. Recent publications proved superior functional outcomes with equal oncologic safety in comparison to conventional open surgery. Its field of application may extend to the nasopharynx and skull base surgery. The preliminary results are encouraging. This article reviews the current literature on the role of transoral robotic surgery in head and neck cancer.

Socioeconomic groups and cancer risk at death in the Swiss Canton of Vaud.

Data collected by the Cancer Registry of the Canton of Vaud, Switzerland, were used to estimate proportional mortality ratios (PMR) and mortality odds ratios (MOR) for various neoplasms according to social class and sector of occupation (agriculture versus others). Mortality ratios were elevated in lower social classes for cancers of the lung (MOR = 1.18 for social class IV or V vs I or II) and other sites strictly related to tobacco (mouth or pharynx, oesophagus and larynx; MOR = 1.70), and (though not significantly) for cancers of the stomach (MOR = 1.16) and uterus (MOR = 1.30 for cervix and 1.47 for corpus uteri). Furthermore, there was a strong negative social class gradient for thyroid cancer (a neoplasm with particularly elevated incidence and mortality in Switzerland), probably attributable to higher prevalence of iodine deficiency in lower social classes (MOR = 3.17). Positive social class gradients emerged for cancers of the intestines (MOR = 0.77 for social class IV or V), skin (MOR = 0.74) and prostate (MOR = 0.87). Agricultural workers showed decreased ratios for cancers of the lung (MOR = 0.75), cervix uteri (MOR = 0.72) and prostate (MOR = 0.80), and excess mortality from cancers of the upper digestive and respiratory sites (MOR = 1.22), stomach (MOR = 1.18), testis (MOR = 2.05) and lympho-haematopoietic neoplasms, particularly myeloma (MOR = 2.14).

Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.

PURPOSE: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol. EXPERIMENTAL DESIGN: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months. RESULTS: Eight dose levels (40-8,000 μg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 μg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 μg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 μg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days. CONCLUSION: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned.

Place du pathologiste dans la prise en charge néoadjuvante des cancers du sein [Neoadjuvant treatment of breast cancer: implications for the pathologist].

These past few years, neoadjuvant strategy has taken an increasing place in the management of breast cancer patients. This strategy is mainly indicated to obtain a tumour bulk regression allowing a breast conserving surgery in patients that otherwise would have undergone mastectomy. Of note, development of new chemotherapy agents and targeted therapies has critically helped in the progress of neoadjuvant strategy as it is currently associated with better pathological response rates. In this context, the pathologist is at the crossroad of this multidisciplinary process. First, he provides on the initial core needle biopsy the tumour pathological characteristics that are critical for the choice of treatment strategy, i.e. histological type, histological grade, proliferative activity (mitotic count and Ki67/MIB1 index labeling), hormone receptor status (oestrogen receptor and progesterone receptor) and HER2 status. Secondly, the pathologist evaluates the pathological response and the status of surgical margins with regards to the residual tumour on the surgical specimen after neoadjuvant treatment. These parameters are important for the management of the patient, since it has been shown that complete pathological response is associated with improved disease free survival. Several grading systems are used to assess the pathological response in breast and axillary lymph nodes. The most frequently used in France are currently the systems described by Sataloff et al. and Chevallier et al. In this review, we detail the different steps involving the pathologist in neoadjuvant setting, with special regards to the quality process and future perspectives such as emerging predictive biomarkers.

Représentations sociales et représentations intimes de la maladie. Quelques réflexions d'un clinicien [Social and private representations of cancer. A clinician's point of view]

This paper discusses social representations in scientific communications and private ones that are linked to the individual imagination. Social representations, in a limited sense, are useful for the development of preventive messages, but of little benefit to clinical work. We highlight some non-explicit aspects of scientific discourse that impact on treatment: projected beliefs and values. We tackle the relationship between the concepts of representation, imagination, identity and temporality in the individual approach of the cancer patient.

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies

Background: Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics. Objective: To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias. Design, Setting, and Participants: A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArrayH NT Cycler. Outcome Measurements and Statistical Analysis: Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer. Results and Limitations: We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics. Conclusion: Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.

Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 16 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.

A comparison of Bayesian and frequentist approaches to incorporating external information for the prediction of prostate cancer risk.

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)-replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta-analysed external SNP effect estimates - one via a weighted PCa 'risk' score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver-operating-characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer.

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving &gt; or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late &gt; or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.