Tag: neoplasms

Article of the Month: Further Evidence that Bladder Cancer Patients should Stop Smoking

July 6, 2016/by admin Z.9

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post. Smoking in a daily basis can affect your lungs, make sure to improve your indoor air quality just by checking out the latest blaux portable ac reviews.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Trends in the risk of second primary cancer among bladder cancer survivors: a population-based cohort of 10 047 patients

Joris Muller*,†, Pascale Grosclaude‡,§, Benedicte Lapotre-Ledoux§,¶, Anne-Sophie Woronoff§,**, Anne-Valerie Guizard§,††, Simona Bara§,‡‡, Marc Colonna§,§§, Xavier Troussard§,¶¶, Veronique Bouvier§,***, Brigitte Tretarre§,†††, Michel Velten*,†,§,‡‡‡ and Jeremie Jegu*,†,§

*Bas-Rhin Cancer Registry, EA 3430, FMTS, University of Strasbourg, †Department of Public Health, University Hospital of Strasbourg, Strasbourg, ‡Tarn Cancer Registry, Albi, §

Francim: Reseau francais des registres des cancers, Toulouse, ¶Somme Cancer Registry, Department of Hygiene and Public Health, University Hospital of Amiens, Amiens, **Doubs and Belfort Territory Cancer Registry, University Hospital of Besancon, Besancon, ††Calvados General Cancer Registry, Cancers & Preventions, U 1086 Inserm, Francois Baclesse Centre, Caen, ‡‡Manche Cancer Registry, Cotentin Hospital, Cherbourg-Octeville, §§Isere Cancer Registry, University Hospital of Grenoble, Grenoble, ¶¶Basse-Normandie Haematological Malignancies Cancer Registry, University Hospital of Caen, ***Calvados Digestive Cancer Registry, Cancers & Preventions, U 1086 Inserm, Francois Baclesse Centre, Caen, †††Herault Cancer Registry, Research Center, Montpellier , and ‡‡‡Department of Epidemiology and Biostatistics, Paul Strauss Center, Strasbourg, France

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Objectives

To determine whether the risk of second primary cancer (SPC) among patients with bladder cancer (BCa) has changed over past years.

Materials and Methods

Data from 10 French population-based cancer registries were used to establish a cohort of 10 047 patients diagnosed with a first invasive (≥T1) BCa between 1989 and 2004 and followed up until 2007. An SPC was defined as the first subsequent primary cancer occurring at least 2 months after a BCa diagnosis. Standardized incidence ratios (SIRs) of metachronous SPC were calculated. Multivariate Poisson regression models were used to assess the direct effect of the year of BCa diagnosis on the risk of SPC.

Results

The risk of new malignancy among BCa survivors was 60% higher than in the general population (SIR 1.60, 95% confidence interval [CI] 1.51–1.68). Male patients presented a high risk of SPC of the lung (SIR 3.12), head and neck (SIR 2.19) and prostate (SIR 1.54). In multivariate analyses adjusted for gender, age at diagnosis and follow-up, a significant increase in the risk of SPC of the lung was observed over the calendar year of BCa diagnosis (P for linear trend 0.010), with an SIR increasing by 3.7% for each year (95% CI 0.9–6.6%); however, no particular trend was observed regarding the risk of SPC of the head and neck (P = 0.596) or the prostate (P = 0.518).

Conclusions

As the risk of SPC of the lung increased between 1989 and 2004, this study contributes more evidence to support the promotion of tobacco smoking cessation interventions among patients with BCa.

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Editorial: Analysis of Genetics to Identify Susceptibility to Secondary Malignancies in Patients with BCa

July 6, 2016/by Yair Lotan

A study by Muller et al. [1] evaluated a cohort of 10 047 patients diagnosed with a first invasive (≥T1) bladder cancer and found that independent of gender and age, the risk of subsequent lung cancer was increased. This is not surprising considering the strong association of both bladder and lung cancer with tobacco, which is the main risk factor for both malignancies. While the authors limited their analysis to patients with invasive disease, the same association of bladder and lung cancer probably holds true for patients with non-invasive disease. An important question this raises is whether urologists should be more proactive in screening for lung cancer in their patients with bladder cancer. While chest radiographs are commonly used to monitor patients who undergo cystectomy, they are not routinely used for patients with non-invasive disease. Furthermore, the recommendations for screening for lung cancer based on the National Lung Cancer Screening Trial (NLST) involve use of low-dose chest CT, which is rarely done routinely by urologists [2]. In the Muller et al. [1] study, despite the large cohort and median follow-up of 3.1 years, there were still only 295 cases of lung cancer. This was three-times the expected incidence but overall a low rate.

One interesting consideration is whether use of genetic factors may be useful to identify which patients might be at higher risk at baseline for subsequent secondary cancers. Currently, single nucleotide polymorphism (SNP) analysis is not used clinically in screening but other genetic abnormalities such as BRCA (BReast Cancer gene) mutations and Lynch syndrome have been used to identify secondary malignancies. However, identifying individuals at higher risk of developing cancer may inform clinicians and allow for a more targeted screening strategy, even in patients of increased baseline risk.

The USA National Cancer Institute performed genome-wide association studies (GWAS) for 49 492 patients with cancer and 34 131 controls to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers [3]. They calculated that at least 24% and 7% of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Only four pairs of cancers had marginally statistically significant correlations including bladder and lung.

While tobacco is the major cause of lung cancer, only ≈10% of smokers develop lung cancer in their lifetime indicating there is significant individual variation in susceptibility to lung cancer. The International Lung Cancer Consortium pooled genotype data for SNPs at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 patients with lung cancer and 14 954 control subjects [4]. Associations between 15q25 and the risk of lung cancer were replicated in White ever-smokers (rs16969968) but there was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, they confirmed statistically significant associations in Whites for both rs2736100 and rs402710 and identified similar associations in Asians. Zhang et al. [5] undertook a gene–smoking interaction analysis in a GWAS of lung cancer in Han Chinese population of 5 408 subjects (2 331 patients and 3 077 controls) using a two-phase designed case-control study. They identified two SNPs associated with lung cancer and smoking, including one with a synergistic interaction (rs4589502) and one with an antagonistic interaction (rs131629).

There have also been several studies evaluating SNPs and risk of bladder cancer. A study of 1 595 patients and 1 760 controls, stratified for smoking habits, found that different SNP combinations were relevant in smokers and non-smokers [6]. In smokers, polymorphisms involved in detoxification of cigarette smoke carcinogens were most relevant (GSTM1 [glutathione S-transferase μ1], rs11892031), in contrast to those in non-smokers where MYC (v-myc avian myelocytomatosis viral oncogene homolog) and APOBEC3A (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A) near polymorphisms (rs9642880, rs1014971) were the most influential. A study of genome-wide interaction of smoking and bladder cancer risk based on data from 3 002 patients and 4 411 controls with validation in a separate dataset identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use [7]. These studies of genetic polymorphisms add evidence regarding the impact of gene–environment interactions, which influence the detrimental effects of tobacco on risk of bladder cancer.

There are other genetic polymorphisms that have been found to increase risk of tobacco-related malignancies. A study of polymorphisms inNAT2 (N-acetyltransferase 2 [arylamine N-acetyltransferase]), GSTM1, NAT1, GSTT1 (GST θ1), GSTM3, and GSTP1 (GST π1) in 1 150 patients with bladder cancer and 1 149 controls found that compared with NAT2 rapid or intermediate acetylators, NAT2 slow acetylators had an increased overall risk of bladder cancer (odds ratio 1.4, 95% CI 1.2–1.7), which was stronger for cigarette smokers than for never smokers. No significant associations were found with the other polymorphisms [8]. The overall association for GSTM1 was also robust (P < 0.001) but was not modified by smoking status (P = 0.86).

While it may be too early to apply GWAS to all patients who smoke, a trial focusing on those with other tobacco-related malignancies may identify cohorts where screening for other malignancies is not only effective but also practical.

Read the full article

Yair Lotan, Professor of Urology

Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA

References

1 Muller J, Grosclaude P, Lapotre-Ledoux B et al. Trends in the risk of second primary cancer among bladder cancer survivors: a population-based cohort of 10 047 patients. BJU Int 2016; 118: 53–9

2 National Lung Screening Trial Research Team, Aberle DR, Adams AM et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365: 395–409

3 Sampson JN, Wheeler WA, Yeager M et al. Analysis of heritability and shared heritability based on genome-wide association studies for thirteen cancer types. J Natl Cancer Inst 2015; 107: pii: djv279. doi: 10.1093/jnci/djv279

4 Truong T, Hung RJ, Amos CI et al. Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium. J Natl Cancer Inst 2010; 102: 959–71

5 Zhang R, Chu M, Zhao Y et al. A genome-wide gene-environment interaction analysis for tobacco smoke and lung cancer susceptibility. Carcinogenesis 2014; 35: 1528–35

6 Schwender H, Selinski S, Blaszkewicz M et al. Distinct SNP combinations confer susceptibility to urinary bladder cancer in smokers and non-smokers. PLoS One 2012; 7: e51880

7 Figueroa JD, Han SS, Garcia-Closas M et al. Genome-wide interaction study of smoking and bladder cancer risk. Carcinogenesis 2014; 35: 1737–44

8 Garcia-Closas M, Malats N, Silverman D et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 2005; 366: 649–59

Article of the Week: Testosterone Therapy and Cancer Risk

February 25, 2015/by admin Z.9

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Michael Eisenberg discussing his paper.

If you only have time to read one article this week, it should be this one.

Testosterone Therapy and Cancer Risk

Michael L. Eisenberg*†, Shufeng Li*‡, Paul Betts§, Danielle Herder¶, Dolores J. Lamb¶ and Larry I. Lipshultz¶

Departments of *Urology, †Obstetrics/Gynecology and ‡Dermatology, Stanford University School of Medicine, Stanford, CA, §Cancer Epidemiology and Surveillance Branch, Texas Cancer Registry, Texas Department of State Health Services, Austin, TX, and ¶Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

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OBJECTIVE

To determine if testosterone therapy (TT) status modifies a man’s risk of cancer.

PATIENTS AND METHODS

The Urology clinic hormone database was queried for all men with a serum testosterone level and charts examined to determine TT status. Patient records were linked to the Texas Cancer Registry to determine the incidence of cancer. Men accrued time at risk from the date of initiating TT or the first office visit for men not on TT. Standardised incidence rates and time to event analysis were performed.

RESULTS

In all, 247 men were on TT and 211 did not use testosterone. In all, 47 men developed cancer, 27 (12.8%) were not on TT and 20 (8.1%) on TT. There was no significant difference in the risk of cancer incidence based on TT (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.57–1.9; P = 1.8). There was no difference in prostate cancer risk based on TT status (HR 1.2, 95% CI 0.54–2.50).

CONCLUSION

There was no change in cancer risk overall, or prostate cancer risk specifically, for men aged >40 years using long-term TT.

Read more articles of the week

Editorial: Malignant medication? Testosterone and cancer

February 25, 2015/by Alexander Pastuszak

Testosterone therapy (TTh) in men with hypogonadism is becoming more commonplace among urologists, endocrinologists and even primary practitioners. While the definition of hypogonadism remains a moving target, the literature reflects very clear benefits of TTh in appropriately selected patients. As with any drug, the adverse effect profile helps to dictate the risk:benefit ratio and, over the past several years, numerous, primarily retrospective, analyses have provided mixed insights into the impact of TTh on cardiovascular disease and cancer, specifically prostate cancer.

Eisenberg et al. [1] take a step back from the focus on prostate cancer and evaluate the impact of TTh on general cancer incidence in a cohort of men treated in a single, large-volume andrology practice over 20 years. The authors found no difference in either overall cancer incidence or in the prostate cancer incidence in men on TTh in comparison with men not on TTh. This finding is significant as it supports the hypothesis that testosterone does not harmfully affect either hormonally responsive (prostate cancer) or non-hormonally responsive malignancies. Interestingly, the authors also observe a lower rate of all cancers in men on testosterone therapy. While not statistically significant, this finding is consistent with that of at least one other study focused on prostate cancer, in which men with high-risk prostate cancer receiving exogenous testosterone had a lower recurrence rate than a matched control group [2]. If borne out in future studies, a protective relationship between TTh and cancer would indeed reflect a novel benefit of treatment.

Nevertheless, at this time the jury remains out on a definitive assessment of the effects of TTh on both cancer as well as cardiovascular disease, and will probably continue to do so until controlled, prospective studies are completed. Numerous, mostly retrospective studies have examined the effects of endogenous testosterone and of the administration of exogenous testosterone, primarily on prostate cancer. While the details of these studies are beyond the scope of the present editorial, their findings have varied with regard to whether testosterone does or does not have effects on cancer incidence, biopsy findings, grade, recurrence rates and margin status, preventing a clear perspective on the effects of testosterone on cancer. Similarly, studies evaluating the impact of TTh on cardiovascular disease have also widely varied in their conclusions [3, 4]. Several recent large retrospective studies have found a detrimental relationship between TTh and cardiovascular disease in specific male populations, but have come under withering criticism from the community, with significant doubts cast regarding the veracity of their findings [5, 6].

The growing popularity of TTh has subjected it to a level of scrutiny applied to few other medications, resulting in a slew of peer-reviewed publications of varying quality and conclusions. In the effort to safeguard patients, investigators have hurriedly carried out retrospective data evaluation, which, by design, limits compensation for confounding factors and unfortunately results in an overall murky understanding of long-term adverse events related to TTh. Nevertheless, the clinical benefits of TTh are clear, and many patients are satisfied with the results of treatment. While physicians should remain the stewards of patient care, informed consent and a patient’s acceptance of both the known as well as the unknown risks of testosterone treatment should continue to be an integral part of the initiation and continuation of TTh, until additional high-quality data from clinical trials become available in the coming years.

Read the full article

Alexander W. Pastuszak

Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

References

1 Eisenberg ML, Li S, Betts P et al. Testosterone therapy and cancer risk. BJU Int 2015; 115: 317–21

2 Pastuszak AW, Pearlman AM, Lai WS et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190: 639–44

3 Basaria S, Coviello AD, Travison TG et al. Adverse events associated with testosterone administration. NEnglJMed2010; 363: 109–22

4 Shores MM, Smith NL, Forsberg CW et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012; 97: 2050–8

5 Vigen R, O’Donnell CI, Baron AE et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013; 310: 1829–36

6 Finkle WD, Greenland S, Ridgeway GK et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014; 9: e85805