Impact of Advanced Radiotherapy on Second Primary Cancer Risk in Prostate Cancer Survivors: A Nationwide Cohort Study

Marie-Christina Jahreiß; Wilma D Heemsbergen; Bo van Santvoort; Mischa Hoogeman; Maarten Dirkx; Floris J Pos; Tomas Janssen; Andre Dekker; Ben Vanneste; Andre Minken; Carel Hoekstra; Robert J Smeenk; Inge M van Oort; Chris H Bangma; Luca Incrocci; Katja K H Aben

doi:10.3389/fonc.2021.771956

Impact of Advanced Radiotherapy on Second Primary Cancer Risk in Prostate Cancer Survivors: A Nationwide Cohort Study

Front Oncol. 2021 Nov 26:11:771956. doi: 10.3389/fonc.2021.771956. eCollection 2021.

Authors

Marie-Christina Jahreiß¹, Wilma D Heemsbergen¹, Bo van Santvoort², Mischa Hoogeman¹, Maarten Dirkx¹, Floris J Pos³, Tomas Janssen³, Andre Dekker⁴, Ben Vanneste⁴, Andre Minken⁵, Carel Hoekstra⁵, Robert J Smeenk⁶, Inge M van Oort⁷, Chris H Bangma⁸, Luca Incrocci¹, Katja K H Aben^{2

9}

Affiliations

¹ Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
² Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, Netherlands.
³ The Netherlands Cancer Institute, Radiation Oncology, Amsterdam, Netherlands.
⁴ Department of Radiation Oncology (Maastro), GROW Institute for Oncology and Developmental Biology, Maastricht, Netherlands.
⁵ Department of Radiation Oncology, Radiotherapiegroep, Deventer, Netherlands.
⁶ Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands.
⁷ Department of Urology, Radboud University Medical Center, Nijmegen, Netherlands.
⁸ Department of Urology, Erasmus University Medical Center, Rotterdam, Netherlands.
⁹ Research Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Abstract

Purpose: External Beam Radiotherapy (EBRT) techniques dramatically changed over the years. This may have affected the risk of radiation-induced second primary cancers (SPC), due to increased irradiated low dose volumes and scatter radiation. We investigated whether patterns of SPC after EBRT have changed over the years in prostate cancer (PCa) survivors.

Materials and methods: PCa survivors diagnosed between 1990-2014 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were divided in three time periods, representing 2-dimensional Radiotherapy (RT), 3-dimensional conformal RT (3D-CRT), and the advanced RT (AdvRT) era. Standardized incidence ratios (SIR) and absolute excess risks (AER) were calculated to estimate relative and excess absolute SPC risks. Sub-hazard ratios (sHRs) were calculated to compare SPC rates between the EBRT and prostatectomy cohort. SPCs were categorized by subsite and anatomic region.

Results: PCa survivors who received EBRT had an increased risk of developing a solid SPC (SIR=1.08; 1.05-1.11), especially in patients aged <70 years (SIR=1.13; 1.09-1.16). Pelvic SPC risks were increased (SIR=1.28; 1.23-1.34), with no obvious differences between the three EBRT eras. Non-pelvic SPC were only significantly increased in the AdvRT era (SIR=1.08; 1.02-1.14), in particular for the 1-5 year follow-up period. Comparing the EBRT cohort to the prostatectomy cohort, again an increased pelvic SPC risk was found for all EBRT periods (sHRs= 1.61, 1.47-1.76). Increased non-pelvic SPC risks were present for all RT eras and highest for the AdvRT period (sHRs=1.17, 1.06-1.29).

Conclusion: SPC risk in patients with EBRT is increased and remained throughout the different EBRT eras. The risk of developing a SPC outside the pelvic area changed unfavorably in the AdvRT era. Prolonged follow-up is needed to confirm this observation. Whether this is associated with increased irradiated low-dose volumes and scatter, or other changes in clinical EBRT practice, is the subject of further research.

Keywords: advanced external beam radiotherapy; prostate cancer; second primary cancer; survivorship; three-dimensional conformal radiotherapy.