Risk of second primary cancer in patients treated with radiotherapy for rectal cancer.
BACKGROUND
Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR).


METHODS
Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not.


RESULTS
A total of 13 457 patients were included in this study; 7024 (52·2 per cent) received RT and 6433 (47·8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1·03; 95 per cent c.i. 0·92 to 1·15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1·33, 1·01 to 1·74) but not within (HR 1·11, 0·73 to 1·67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 0·68, 0·51 to 0·91).


CONCLUSIONS
Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
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A
Martling
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Smedby
Departments of Surgical Science, Uppsala University, Uppsala, Sweden.
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H
Birgisson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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H
Olsson
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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F
Granath
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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A
Ekbom
Departments of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
B
B
Glimelius
D000230:Adenocarcinoma / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden