Urologic Oncology: Seminars and Original Investigations
Original articleRenal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial
Introduction
Renal-cell carcinoma (RCC) represents the sixth and eighth most common cancer in men and women, respectively [1]. In 2014, an estimated 63,920 new cases of RCC was diagnosed with 39,140 and 24,760 cases in men and women, respectively. There was also an estimated 13,860 deaths. The incidence of RCC has been increasing worldwide in part because detection of more small renal masses but mortality has been generally stable [2]. This is in large part a consequence of the fact that 33% of new RCCs are metastatic at diagnosis [3]. There are several known risk factors for RCC including increased age, male sex, smoking, and hypertension [4]. Obesity may also have a role but the effect is more controversial [4]. The incidence rises with age with estimated risk of 0.3% in men between ages 50 and 59 years rising to 1.3% for ages 70 years and older [1]. In women, the rates are lower with an estimated risk of 0.2% between ages 50 and 59 years rising to 0.7% for ages 70 years and older. Men are at a higher risk with male to female ratio of 2:1 [3].
Smoking is an established risk factor for RCC based on meta-analyses of case–control studies [5], [6]. However, there is considerable variability regarding the actual increased risk based on smoking duration and intensity [6]. Several large cohort studies have also found an association of obesity and hypertension with risk of RCC [7], [8], [9].
To develop strategies for prevention or screening of kidney cancer, a better understanding of the effect of different risks on incidence would be of value. Both the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and National Lung Screening Trial (NLST) performed a longitudinal evaluation of large populations and tracked secondary malignancies. Using these datasets, we evaluated the effect of age, sex, ethnicity, body mass index (BMI), and smoking intensity on the likelihood of developing RCC [10], [11].
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Material and methods
The study designs of PLCO and NLST have been described previously [10], [11]. Both the trials tracked diagnosis of other malignancies during the trial period. The PLCO included 154,900 participants from the general population aged 55 through 74 years, who were enrolled between 1993 and 2001 after recruitment through mass mailing [10]. Eligibility criteria included a negative history of prostate, lung, colorectal, and ovarian cancer. Participants were randomized to screening vs. no screening for
Statistical analysis
Differences in person–time incidence rates between men and women stratified by race, age, smoking exposure, and lung cancer diagnosis were computed with the chi-square test for both trials separately. Further, proportional hazards models were computed separately to identify high-risk groups. All statistical analyses were conducted with SAS version 9.2. CIs for rate ratios for incidence were calculated with the use of asymptotic methods, assuming a normal distribution for the logarithm of the
Results
Overall, 701/154,118 and 190/53,242 kidney cancers were detected in PLCO and NLST, respectively. From the PLCO trial, 78,183 women and 76,636 men were included in our analyses. Overall incidence of RCC was 0.28/1,000 person years for women and 0.56/1,000 person years for men (Table 1). In the NLST, 21,915 women and 31,517 men were included in our analyses and incidence of RCC was significantly higher in men compared with women in this study set as well (0.73 vs. 0.35/1,000 Person y,
Discussion
Despite the increasing use of cross-sectional imaging, approximately a third of newly diagnosed RCCs are metastatic at presentation [3]. Advancements in targeted agents provide a small survival benefit but overall mortality from RCC has not decreased [3]. Although the increase in incidentally detected small renal masses has not affected survival, it is possible that a targeted screen in high-risk cohorts may improve the yield of cancer detection.
As such, rational screening for RCC may be a
Conclusions
Age over 60 years, male sex, smoking intensity, and obesity affect the risk of kidney cancer. Sex differences in RCC are not explained by differences in smoking or obesity. Identification of a high-risk population may allow a pilot study of rational screening for RCC.
Acknowledgments
The authors thank the National Cancer Institute for access to NCI׳s data collected by the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The authors thank the National Cancer Institute for access to NCI׳s data collected by the National Lung Screening Trial. The statements contained herein are solely those of the authors and do not represent or imply concurrence or endorsement by NCI.
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Cited by (25)
Impact of Patients’ Gender on Efficacy of Immunotherapy in Patients With Metastatic Kidney Cancer: A Systematic Review and Meta-analysis
2020, Clinical Genitourinary CancerCitation Excerpt :For example, male gender has been reported to be an independent predictor of high-grade renal cell carcinoma (RCC) as well as to be linked to worse cancer control outcomes and earlier recurrence after treatment for localized RCC. On the other hand, female gender has been associated with worse cancer-specific mortality in disease recurrence and in the metastatic setting.1-5 These data suggest that females do better at initial diagnosis and have a worse outcome in RCC recurrence or metastasis, but gender-specific differences in outcomes and treatment remain an interesting but under-investigated issue in metastatic RCC (mRCC).6
Epidemiology of Renal Cell Carcinoma [Figure presented]
2019, European UrologyCitation Excerpt :In the VITAL study, smoking was independently associated with RCC (>37.5 pack-years vs never: HR 1.58, 95% CI 1.09–2.29) [10]. Similarly, in the PLCO trial, the intensity of smoking was confirmed to be significantly associated with a higher risk of developing RCC and with a higher risk of high-grade RCC [13]. Moreover, relative risk is directly associated with smoking duration and decreases over time after cessation.
Modifiable risk factors to reduce renal cell carcinoma incidence: Insight from the PLCO trial
2018, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :The authors specifically mention perioperative blood pressure ≥ 160/100 mmHg to be harmful, but did not identify an association with smoking. Lotan et al. [41] used the PLCO study to propose the identification of a screening population at high-risk for developing kidney cancer, which included age over 60 years, male sex, smoking intensity, and obesity. A study showed a higher 5-year cancer-specific survival rate was significantly seen in patients with incidental RCC than for symptomatic tumors [42].