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Radiotherapy for prostate cancer may result in an increased risk of secondary malignancies of the bladder, colon, and rectum, according to findings of a systematic review and meta-analysis.
The unadjusted odds ratios for secondary bladder, colorectal, and rectal cancers in patients exposed to radiotherapy, compared with those not exposed, were 1.39 (95% CI, 1.12-1.71), 1.68 (1.33-2.12), and 1.62 (1.26-2.08), respectively. Differences in absolute risks for cases and controls were low, ranging from –0.9 to 1.9 cancers per 100 patients, and arose from variation in type of radiotherapy, comparator group, and lag time.
The findings, based on a relatively small number of studies with limited adjustments made for confounders, point to the need for future studies, according to the investigators. They described the implications of the findings for making treatment decisions with patients.
“In particular, for patients with a long life expectancy of 20 years or more, the possibility of secondary malignancy related to radiation needs to be included in management discussions. We acknowledge, however, that further studies are required before conclusive implication of the association between radiotherapy and secondary malignancy in these patients,” wrote Dr. Christopher J.D. Wallis of the University of Toronto and his colleagues (BMJ 2016 March 2. doi: 10.1136/bmj.i851).
Evidence suggests that irradiation of the prostate may contribute to carcinogenesis outside the irradiated area by radiation scatter, as well as the bystander effect, described as changes in gene expression due to an increase in reactive oxygen species. The researchers examined the association between radiotherapy and secondary malignancies of the bladder, colorectal tract, lung, and hematologic systems, and found no consistent evidence for associations with lung and hematologic cancers.
The systematic review and meta-analysis involved 9 studies (n = 555,873) for bladder cancer, 10 (n = 228,965) for colorectal cancer, and 8 (n = 157,239) for rectal cancer. Of the 21 reports total, 18 were multi-institutional and 3 were single-center studies. The lag period before outcome determination varied considerably, as did the comparator groups, with 13 studies (62%) designating patients treated with surgery as comparators, and 8 studies designating patients with no radiation or no radiation and no surgery as controls.
The results were similar when the analysis was restricted to studies with 5-year or 10-year lag periods. Notably, for bladder and rectal cancers, risk increased with longer lag time: from 1.3 to 1.89 for a 5-year and 10-year period, respectively, for bladder cancer and from 1.68 to 2.2 for rectal cancer.
Risks associated with brachytherapy were lower than for external beam radiotherapy.
The comprehensive systematic review and meta-analysis by Wallis et al. suggests an increased risk of bladder (odds ratio, 1.39), rectal (OR, 1.62), and colorectal (OR, 1.68) cancers subsequent to radiotherapy for prostate cancer. Despite the increased relative risks, absolute risk remains small, and discovered cancers, while still requiring treatment, might not be lethal. Indeed, there appears to be no survival difference between men with bladder cancers linked to previous prostate cancer treated with radiation vs. prostate cancer treated with surgery.
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Dr. Anthony L. Zietman |
The current study found that brachytherapy (high radiation dose to a small volume of tissue) was not associated with an increased risk for secondary malignancies, which supports the move toward even more tightly targeted external radiation techniques.
As for real world implications of the findings, the observed increase in risk may have a bigger influence in treatment decisions for young patients with few comorbidities than it would for older patients or those with competing health risks.
“This study confirms our belief that second malignancy should be added to the already long list of avoidable hazards associated with treatment for those men with low-risk prostate cancer who simply need no treatment at all. Concern about second malignancies should not, however, stand in the way of an effective and well-studied treatment being given to men with higher-grade, lethal prostate cancer for whom the potential benefit simply dwarfs the risk,” wrote Dr. Christine E. Eyler and Dr. Anthony L. Zietman.
Dr. Eyler is a clinical fellow in radiation oncology at Massachusetts General Hospital, Boston. Dr. Zietman is professor of radiation oncology at Massachusetts General Hospital. These remarks were part of an editorial accompanying a report in the British Medical Journal (2016 March 2. doi: 10.1136/bmj.i1073).
The comprehensive systematic review and meta-analysis by Wallis et al. suggests an increased risk of bladder (odds ratio, 1.39), rectal (OR, 1.62), and colorectal (OR, 1.68) cancers subsequent to radiotherapy for prostate cancer. Despite the increased relative risks, absolute risk remains small, and discovered cancers, while still requiring treatment, might not be lethal. Indeed, there appears to be no survival difference between men with bladder cancers linked to previous prostate cancer treated with radiation vs. prostate cancer treated with surgery.
|
Dr. Anthony L. Zietman |
The current study found that brachytherapy (high radiation dose to a small volume of tissue) was not associated with an increased risk for secondary malignancies, which supports the move toward even more tightly targeted external radiation techniques.
As for real world implications of the findings, the observed increase in risk may have a bigger influence in treatment decisions for young patients with few comorbidities than it would for older patients or those with competing health risks.
“This study confirms our belief that second malignancy should be added to the already long list of avoidable hazards associated with treatment for those men with low-risk prostate cancer who simply need no treatment at all. Concern about second malignancies should not, however, stand in the way of an effective and well-studied treatment being given to men with higher-grade, lethal prostate cancer for whom the potential benefit simply dwarfs the risk,” wrote Dr. Christine E. Eyler and Dr. Anthony L. Zietman.
Dr. Eyler is a clinical fellow in radiation oncology at Massachusetts General Hospital, Boston. Dr. Zietman is professor of radiation oncology at Massachusetts General Hospital. These remarks were part of an editorial accompanying a report in the British Medical Journal (2016 March 2. doi: 10.1136/bmj.i1073).
The comprehensive systematic review and meta-analysis by Wallis et al. suggests an increased risk of bladder (odds ratio, 1.39), rectal (OR, 1.62), and colorectal (OR, 1.68) cancers subsequent to radiotherapy for prostate cancer. Despite the increased relative risks, absolute risk remains small, and discovered cancers, while still requiring treatment, might not be lethal. Indeed, there appears to be no survival difference between men with bladder cancers linked to previous prostate cancer treated with radiation vs. prostate cancer treated with surgery.
|
Dr. Anthony L. Zietman |
The current study found that brachytherapy (high radiation dose to a small volume of tissue) was not associated with an increased risk for secondary malignancies, which supports the move toward even more tightly targeted external radiation techniques.
As for real world implications of the findings, the observed increase in risk may have a bigger influence in treatment decisions for young patients with few comorbidities than it would for older patients or those with competing health risks.
“This study confirms our belief that second malignancy should be added to the already long list of avoidable hazards associated with treatment for those men with low-risk prostate cancer who simply need no treatment at all. Concern about second malignancies should not, however, stand in the way of an effective and well-studied treatment being given to men with higher-grade, lethal prostate cancer for whom the potential benefit simply dwarfs the risk,” wrote Dr. Christine E. Eyler and Dr. Anthony L. Zietman.
Dr. Eyler is a clinical fellow in radiation oncology at Massachusetts General Hospital, Boston. Dr. Zietman is professor of radiation oncology at Massachusetts General Hospital. These remarks were part of an editorial accompanying a report in the British Medical Journal (2016 March 2. doi: 10.1136/bmj.i1073).
Radiotherapy for prostate cancer may result in an increased risk of secondary malignancies of the bladder, colon, and rectum, according to findings of a systematic review and meta-analysis.
The unadjusted odds ratios for secondary bladder, colorectal, and rectal cancers in patients exposed to radiotherapy, compared with those not exposed, were 1.39 (95% CI, 1.12-1.71), 1.68 (1.33-2.12), and 1.62 (1.26-2.08), respectively. Differences in absolute risks for cases and controls were low, ranging from –0.9 to 1.9 cancers per 100 patients, and arose from variation in type of radiotherapy, comparator group, and lag time.
The findings, based on a relatively small number of studies with limited adjustments made for confounders, point to the need for future studies, according to the investigators. They described the implications of the findings for making treatment decisions with patients.
“In particular, for patients with a long life expectancy of 20 years or more, the possibility of secondary malignancy related to radiation needs to be included in management discussions. We acknowledge, however, that further studies are required before conclusive implication of the association between radiotherapy and secondary malignancy in these patients,” wrote Dr. Christopher J.D. Wallis of the University of Toronto and his colleagues (BMJ 2016 March 2. doi: 10.1136/bmj.i851).
Evidence suggests that irradiation of the prostate may contribute to carcinogenesis outside the irradiated area by radiation scatter, as well as the bystander effect, described as changes in gene expression due to an increase in reactive oxygen species. The researchers examined the association between radiotherapy and secondary malignancies of the bladder, colorectal tract, lung, and hematologic systems, and found no consistent evidence for associations with lung and hematologic cancers.
The systematic review and meta-analysis involved 9 studies (n = 555,873) for bladder cancer, 10 (n = 228,965) for colorectal cancer, and 8 (n = 157,239) for rectal cancer. Of the 21 reports total, 18 were multi-institutional and 3 were single-center studies. The lag period before outcome determination varied considerably, as did the comparator groups, with 13 studies (62%) designating patients treated with surgery as comparators, and 8 studies designating patients with no radiation or no radiation and no surgery as controls.
The results were similar when the analysis was restricted to studies with 5-year or 10-year lag periods. Notably, for bladder and rectal cancers, risk increased with longer lag time: from 1.3 to 1.89 for a 5-year and 10-year period, respectively, for bladder cancer and from 1.68 to 2.2 for rectal cancer.
Risks associated with brachytherapy were lower than for external beam radiotherapy.
Radiotherapy for prostate cancer may result in an increased risk of secondary malignancies of the bladder, colon, and rectum, according to findings of a systematic review and meta-analysis.
The unadjusted odds ratios for secondary bladder, colorectal, and rectal cancers in patients exposed to radiotherapy, compared with those not exposed, were 1.39 (95% CI, 1.12-1.71), 1.68 (1.33-2.12), and 1.62 (1.26-2.08), respectively. Differences in absolute risks for cases and controls were low, ranging from –0.9 to 1.9 cancers per 100 patients, and arose from variation in type of radiotherapy, comparator group, and lag time.
The findings, based on a relatively small number of studies with limited adjustments made for confounders, point to the need for future studies, according to the investigators. They described the implications of the findings for making treatment decisions with patients.
“In particular, for patients with a long life expectancy of 20 years or more, the possibility of secondary malignancy related to radiation needs to be included in management discussions. We acknowledge, however, that further studies are required before conclusive implication of the association between radiotherapy and secondary malignancy in these patients,” wrote Dr. Christopher J.D. Wallis of the University of Toronto and his colleagues (BMJ 2016 March 2. doi: 10.1136/bmj.i851).
Evidence suggests that irradiation of the prostate may contribute to carcinogenesis outside the irradiated area by radiation scatter, as well as the bystander effect, described as changes in gene expression due to an increase in reactive oxygen species. The researchers examined the association between radiotherapy and secondary malignancies of the bladder, colorectal tract, lung, and hematologic systems, and found no consistent evidence for associations with lung and hematologic cancers.
The systematic review and meta-analysis involved 9 studies (n = 555,873) for bladder cancer, 10 (n = 228,965) for colorectal cancer, and 8 (n = 157,239) for rectal cancer. Of the 21 reports total, 18 were multi-institutional and 3 were single-center studies. The lag period before outcome determination varied considerably, as did the comparator groups, with 13 studies (62%) designating patients treated with surgery as comparators, and 8 studies designating patients with no radiation or no radiation and no surgery as controls.
The results were similar when the analysis was restricted to studies with 5-year or 10-year lag periods. Notably, for bladder and rectal cancers, risk increased with longer lag time: from 1.3 to 1.89 for a 5-year and 10-year period, respectively, for bladder cancer and from 1.68 to 2.2 for rectal cancer.
Risks associated with brachytherapy were lower than for external beam radiotherapy.
FROM BRITISH MEDICAL JOURNAL
Key clinical point: Radiotherapy for prostate cancer was associated with a higher risk of secondary malignancies of the bladder, colon, and rectum.
Major finding: The unadjusted odds ratios for secondary bladder, colorectal, and rectal cancers in patients exposed to radiotherapy, compared with those not exposed, were 1.39 (95% CI, 1.12-1.71), 1.68 (1.33-2.12), and 1.62 (1.26-2.08), respectively.
Data sources: The systematic review and meta-analysis of 21 reports involved 9 studies (n = 555,873) for bladder cancer, 10 (n = 228,965) for colorectal cancer, and 8 (n = 157,239) for rectal cancer.
Disclosures: Dr. Wallis and coauthors reported having no relevant financial disclosures.
