## 3 Radiotherapy for Rectal Cancer
### Comparison of Radiotherapy Techniques
There was no increased risk for secondary primary cancer between the RT and surgery-alone groups (Hazard Ratio [HR] 1.03 and 1.15, respectively). In the randomized trials, a slight increase in risk was observed among patients who received RT compared to those who did not, in non-RT-associated sites (HR = 1.33, 95% CI = 1.01 to 1.74). Short-course vs. long-course RT did not show any differences. The most common secondary primary cancers outside the irradiated volume were colonic, lung, breast, and squamous cell skin cancers. The most common secondary primaries in RT-associated sites were prostate and urinary bladder cancers, followed by uterine/cervical cancer. The risk of prostate cancer was significantly reduced in men who received RT (HR 0.68, 0.51-0.91), as was the risk of prostate cancer-specific death. Women who received RT did not show a significantly increased risk of uterine/cervical cancer (HR 1.84, 0.92-3.66). Although there was a tendency toward an increased risk with longer follow-up, the risk was not significantly increased at any time interval in this study. [PERSON] and [PERSON] [45] analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database of 20,910 patients with rectal carcinoma, who developed 3024 primary malignancies. Patients who received RT had a significantly decreased risk of developing secondary malignancies (12% vs. 16%). The risk for prostate cancer decreased (HR = 0.63), while the risk for uterine and cervical cancers increased (HR = 2.5). A more recent study from the SEER database [46] involving 77,484 patients who underwent surgery for locally advanced rectal carcinoma, including 34,114 irradiated patients, found no association between RT and increased risk for secondary malignancies (HR = 0.97). This study confirmed the decreased risk for prostate cancer in men and increased risk for endometrial carcinoma in women, but not for cervical cancer. Increased risks for lung and bladder cancers, as well as lymphomas, were noted in all patients. Another study [16] retrieved data for 29,027 rectal cancer patients from the Netherlands population-based cancer registry, 4398 of whom developed a second primary cancer. Consistent with previous studies, they demonstrated a marginal overall increased risk in the RT group of patients. They also found a decreased risk for prostate cancer in the RT cohort (HR = 0.54) and an increased risk for gynecological cancers (HR = 1.49). [PERSON] et al. [47] compared the risk of second primary cancers in pre- and postoperative RT to surgically treated-only patients using data from the SEER database. The risk for developing any type of second primary cancer was 12% higher in patients receiving preoperative RT, and 33% lower for patients receiving postoperative RT compared to those who had surgery only. The risk for thyroid cancers and leukemia was higher in patients receiving any RT, but lower for prostate cancer. [PERSON] et al. [48] used Taiwan's National Health Insurance Research Database to collect data for 28,220 rectal cancer patients. The cumulative incidence of second primary cancers was 7.8% at 10 years. Analysis of preoperative short- and long-course RT, postoperative RT, and surgery-only cohorts did not show any differences in second primary cancers. They also found a decreased risk of prostate cancer in the RT cohort, although it was not statistically significant. Conversely, [PERSON] et al. [49] focused on secondary prostate cancer in men with rectal cancer from the same database, finding a reduced risk for prostate cancer in the RT group of patients (HR = 0.41). [PERSON] et al. [50] analyzed gynecological second primary tumors in a SEER database study of 20,142 women surgically treated for rectal cancer. The cumulative incidence of second primary gynecological cancers over a follow-up period of thirty years was 4.53% in RT patients and 1.53% in non-RT patients. RT was associated with a significantly higher risk of uterine tumors (HR = 3.06) and ovarian cancer (HR = 2.08).