Risk of mesothelioma following external beam radiotherapy for prostate cancer: a cohort analysis of SEER database

Our plain-English summary of Risk of mesothelioma following external beam radiotherapy for prostate cancer: a cohort analysis of SEER database, by A. Farioli, F.S. Violante, S. Mattioli, et al (Cancer Causes & Control, 2013).

The study

• Authors: A. Farioli, F.S. Violante, S. Mattioli, S. Curti, D. Kriebel
• Journal: Cancer Causes & Control
• Published: 2013;24(8):1535-45
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: To investigate the association between external beam radiotherapy (EBRT) for prostate cancer and mesothelioma using data from the US Surveillance, Epidemiology, and End Results (SEER) cancer registries.

Methods: We analyzed data from the SEER database (1973-2009). We compared EBRT versus no radiotherapy. Incidence rate ratios (IRR) and 95 % confidence intervals (95 % CI) of mesothelioma among prostate cancer patients were estimated with multilevel Poisson models adjusted by race, age, and calendar year. Confounding by asbestos was investigated using relative risk of mesothelioma in each case's county of residence as a proxy for asbestos exposure.

Results: Four hundred and seventy-one mesothelioma cases (93.6 % pleural) occurred in 3,985,991 person-years. The IRR of mesothelioma was increased for subjects exposed to EBRT (1.28; 95 % CI 1.05, 1.55) compared to non-irradiated patients, and a population attributable fraction of 0.49 % (95 % CI 0.11, 0.81) was estimated. The IRR increased with latency period: 0-4 years, IRR 1.08 (95 % CI 0.81, 1.44); 5-9 years, IRR 1.31 (95 % CI 0.93, 1.85); ≥10 years, IRR 1.59 (95 % CI 1.05, 2.42). Despite the fairly strong evidence of association with EBRT, the population attributable rate of mesothelioma was modest-3.3 cases per 100,000 person-years. The cumulative incidence of mesothelioma attributable to EBRT was 4.0/100,000 over 5 years, 24.5/100,000 over 10 years, and 65.0/100,000 over 15 years.

Conclusions: Our study provides evidence that EBRT for prostate cancer is a small but detectable risk factor for mesothelioma. Patients should be advised of risk of radiation-induced second malignancies.

In plain English

This retrospective cohort study followed 570,883 men with first primary invasive prostate cancer in US SEER registries, 1973 to 2009. The authors compared men given external beam radiotherapy (EBRT) as initial treatment with men given no radiotherapy. Over 3,985,991 person-years, 471 mesotheliomas occurred (441 pleural, 21 peritoneal). Compared with men given no radiotherapy, EBRT-treated men had an adjusted incidence rate ratio of 1.28 (95% CI 1.05 to 1.55). The ratio was 1.08 (0.81 to 1.44) 0 to 4 years after diagnosis and 1.59 (1.05 to 2.42) after 10 or more years. Lacking individual asbestos histories, the authors adjusted for each county's mesothelioma risk instead; this did not change the EBRT result. The extra rate with EBRT was 3.31 per 100,000 person-years (95% CI 0.72 to 5.90). Assuming cause and effect, the authors estimated that 0.49% (95% CI 0.11% to 0.81%) of male mesothelioma cases in these registries resulted from EBRT for prostate cancer. The authors concluded that EBRT for prostate cancer is a mesothelioma risk factor but unlikely to have played any significant role in the global mesothelioma epidemic.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study using US cancer registry (SEER) data, analyzed with Poisson regression models
• Who was studied: 570,883 men diagnosed with first primary invasive prostate cancer. They were recorded in the SEER 9 Registries for 1973 to 1991 and the SEER 13 Registries for 1992 to 2009, with the Alaska Natives registry excluded. Follow-up totalled 3,985,991 person-years, and 471 mesothelioma cases occurred.
• Exposure: External beam radiotherapy (EBRT, alone or with brachytherapy) as part of initial prostate cancer treatment, compared with no radiotherapy. A third group received other radiation (radioactive implants, radioisotopes, unspecified). Asbestos exposure was not measured for individuals; each man's county-level mesothelioma relative risk was used as a proxy.
• Main results:
  • Of the 471 mesothelioma cases in the cohort, 441 were pleural, 21 peritoneal, and 9 at other or unspecified sites.
  • Men treated with EBRT (168 cases in 1,137,412 person-years) had an adjusted incidence rate ratio of 1.28 (95% CI 1.05, 1.55). The comparison group was men who received no radiotherapy (281 cases in 2,651,827 person-years).
  • No increase in mesothelioma risk was seen among men given other forms of radiotherapy (adjusted IRR 1.04, 95% CI 0.67, 1.62).
  • For EBRT-treated men, the IRR rose with time since prostate cancer diagnosis: 1.08 (95% CI 0.81, 1.44) at 0 to 4 years, 1.31 (95% CI 0.93, 1.85) at 5 to 9 years, and 1.59 (95% CI 1.05, 2.42) at 10 or more years.
  • The adjusted incidence rate difference for EBRT-treated men versus men with no radiotherapy was 3.31 per 100,000 person-years (95% CI 0.72, 5.90).
  • Men living in counties in the highest tertile of mesothelioma risk had an IRR of 2.98 (95% CI 1.76, 5.03) compared with the lowest tertile. This county measure did not confound the EBRT association: the EBRT IRR was unchanged to 3 decimal places without it.
  • For peritoneal mesothelioma alone (21 cases), the univariate IRR for EBRT was 1.75 (95% CI 0.74, 4.15), with wide confidence intervals.
  • Assuming a causal association, the authors estimated that 0.49% (95% CI 0.11, 0.81%) of mesothelioma cases resulted from EBRT after prostate cancer. This was based on the 7,450 male mesothelioma cases in the SEER registries studied.
  • The estimated cumulative incidence of mesothelioma attributable to EBRT was 4.0 per 100,000 over 5 years, 24.5 per 100,000 over 10 years, and 65.0 per 100,000 over 15 years.
• The authors' conclusion: The authors concluded that their study provides evidence that EBRT for prostate cancer is a risk factor for mesothelioma. Because the absolute increase in risk and the population attributable fraction were small, they believe EBRT is unlikely to have played any significant role in the global mesothelioma epidemic.
• Limitations the authors state:
  • Information on personal characteristics and individual exposures was lacking, so unmeasured confounding was possible.
  • Estimates could not be adjusted for each person's history of asbestos exposure. A county-level proxy was used instead, which the authors say is affected by a high degree of misclassification.
  • The findings could be partly explained if former asbestos workers were more likely to receive EBRT, for example because of other illnesses. After sensitivity analyses, the authors judged this not a major concern.
  • EBRT was recorded only as yes or no, with no dose or treatment-type information, so a dose-response relationship could not be studied.
  • Some men classified as unexposed may have received EBRT later, which the authors say likely biased estimates toward no effect.
  • The latencies studied were shorter than those usually reported for asbestos-related mesothelioma.
  • No immunohistochemistry information was available, so mesothelioma may have been slightly over-diagnosed. The authors consider this unlikely to differ by radiotherapy status.
  • Only 21 peritoneal cases were available, too few for a separate multivariate analysis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, SEER, Epidemiology, Incidence, confidence interval, Confounding, Relative Risk, Asbestos Exposure.

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