IMRT for Prostate Cancer Not Associated With Increased Risk of Second Primary Cancers, Study Finds

In a large cohort of prostate cancer survivors, treatment with intensity-modulated radiotherapy (IMRT) vs 3-dimensional conformal radiation therapy (3DCRT) was not associated with an increased risk of developing second primary solid or hematologic cancers, a study published in JAMA Oncology found.¹

IMRT has become the clinical radiotherapy standard for treating prostate cancer, enabling dose escalation to the tumor and sparing nearby tissue compared with 3DCRT, the authors noted. But IMRT increases scatter radiation to normal tissue, including bone marrow, which could mean a higher risk of developing other cancers as a late adverse effect of radiotherapy.

Whether the type of radiotherapy impacts the risk of subsequent cancers has not been clear. An initial report encompassing 5-year prostate cancer survivors diagnosed from 2002 to 2006 and follow-up through 2011 suggested there may be a reduced risk of later colon and rectal cancers with IMRT compared with 3DCRT.² But the same report analyzed a cohort of 2-year survivors diagnosed between 2022 and 2009 and found no association between the type of radiotherapy and subsequent solid or hematologic cancers, with follow-up through 2011.

The new study addresses the limited follow-up in these analyses by extending the follow-up period through 2015.

A retrospective cohort of male patients diagnosed with first primary nonmetastatic prostate cancer from 2002 to 2013 was identified using data from the Surveillance, Epidemiology and End Results (SEER) Program–Medicare database. The cohort included patients aged 66 to 84 with data reported to 17 SEER registries.

A total of 65,235 2-year prostate cancer survivors were included in the study, with a median age of 72 (66-82) years. In the overall cohort, 63.4% of patients received IMRT, which was more frequently used after 2006, the authors noted. A total of 45,811 5-year prostate cancer survivors with a median age of 72 (66-79) years were included and showed similar patterns to the 2-year survivor group.

Among the 2-year survivors, 1107 second hematologic cancers were diagnosed during a median 4.6-year follow-up, meaning 6.6 years after initial diagnosis. The 10-year cumulative incidence of second cancer after 3DCRT was 2.3% (95% CI, 2.1%-2.6%), and after IMRT was 2.4% (95% CI, 2.2%-2.6%). This suggests that radiotherapy type is not associated with second hematological malignancy in the cohort.

In the cohort of 5-year survivors with a median follow-up of 3.1 (0.003-9.0) years, meaning 8.1 years since initial prostate cancer diagnosis, 2688 patients were diagnosed with second primary solid cancers. The 10-year cumulative incidence was 7.3% (95% CI, 6.9%-7.7%) among 5-year survivors treated with IMRT and 7.5% (95% CI, 7.1%-7.9%) among those treated with 3DCRT. Overall, the HR for IMRT was 0.91 (95% CI, 0.83-0.99).

“The present study’s results, based on larger case counts and a broader range of calendar years, suggest that the inverse association between IMRT vs 3DCRT and risk for all solid cancers as well as colon cancer does not persist in more recent calendar years,” the authors wrote. “This may reflect changes in treatment volume or expansion of IMRT to broader populations (eg, more aggressive disease, increased comorbidities, community oncology centers) over time.”

Limitations of the study included a lack of specific dosimetry information, which prevented analysis of the dose-response association between radiotherapy and second cancer risk, the authors noted. Potential risk factors for second cancers, such as smoking status, were also not known.

“The present cohort study’s results suggest that IMRT for prostate cancer is not associated with an increased risk of second solid or hematologic cancers,” the authors concluded. “The inverse association previously reported for colon cancer was only observed in this analysis among men treated from 2002 to 2005. Further studies are needed to continue monitoring outcomes after IMRT and to incorporate patients treated with proton therapy as its use becomes more widespread.”


Reference

1. Pithadia KJ, Advani PG, Citrin DE, et al. Comparing risk for second primary cancers after intensity-modulated vs 3-dimensional conformal radiation therapy for prostate cancer, 2002-2015. JAMA Oncol. Published online June 8, 2023. doi:10.1001/jamaoncol.2023.1638

2. Journy NM, Morton LM, Kleinerman RA, Bekelman JE, Berrington de Gonzalez A. Second primary cancers after intensity-modulated vs 3-dimensional conformal radiation therapy for prostate cancer. JAMA Oncol. 2016;2(10):1368-1370. doi:10.1001/jamaoncol.2016.1368