## 6 Conclusions and Future Perspectives  
The present study reviewed the probability of radiation carcinogenesis as derived from epidemiological and dosimetric data. Many epidemiological studies have reported that the patients undergoing pelvic RT are not subjected to a higher risk for second-cancer induction compared to unirradiated patients with a primary malignancy in the rectum [16; 44; 45; 48; 49]. Other studies characterized the second-cancer risk from RT as elevated [15] or marginally increased [16]. Nearly all of the above studies agree that pelvic irradiation for rectal cancer offers a protective effect against prostate cancer [16; 44; 45; 46; 47; 51; 52]. It has been suggested that RT may target occult prostate carcinomas, as the prostate is often within the primary radiation field, or that RT may suppress hormone excretion from the testicles, which receive low doses of scattered radiation. The participants of several epidemiological studies were irradiated between 1973 and 1999 [15; 44; 45], whereas other studies included patients treated up to 2012 [16; 46; 47; 51; 48; 51]. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Patient Age** & **Organ-At-Risk** & & **Cancer Risk** & \\ \hline  & & **LAR (\%)** & **LBR (\%)** & **RR** \\ \hline
50 & Bowel & 0.10 & 4.01 & 1.025 \\  & Bladder & 0.16 & 2.53 & 1.063 \\
60 & Bowel & 0.05 & 3.61 & 1.014 \\  & Bladder & 0.09 & 2.48 & 1.036 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Relative risk (RR) for bowel and bladder cancer induction following IMRT for rectal carcinoma with 6 MV photon beams. The lifetime attributable risk (LAR) for developing bowel and bladder cancer due to 50 Gy-RT was taken from the work of [PERSON] et al. [18] and the lifetime baseline risk (LBR) from the SEER cancer statistics review of the US population [72]. Advances in treatment planning and delivery have significantly transformed the clinical use of RT for pelvic malignancies over the last two decades. While the conclusions drawn from older studies are valuable, they should be interpreted cautiously in light of modern RT techniques. Earlier data often reflect less precise RT technologies, such as two-dimensional planning and large radiation fields, which exposed surrounding tissues to higher radiation doses and increased the risk of second primary cancers (SPCs) in adjacent organs. Modern RT approaches, including IMRT [43] and proton therapy [73], enhance dose conformality, reduce radiation scatter to critical organs like the bladder and prostate, and improve precision through image-guided RT (IGRT) and adaptive RT [74]. Hypof fractionation and shorter-course RT strategies also optimize treatment delivery and may reduce cumulative radiation doses. Useful information about the second-cancer risk from the conventional 3D-CRT and the modern techniques of IMRT and VMAT have been given by previous dosimetric studies [17; 18; 68]. The effect of the fractionation schedule on the resultant second-cancer risk has been discussed [17; 18]. The use of 3D-CRT instead of the IMRT and VMAT was found to reduce the probability of carcinogenesis to organs, located at distant positions from the treatment volume, as reported by [PERSON] et al. [68]. This may be attributed to the reduced beam-on time with conventional 3D-CRT relative to that with modern intensity-modulated RT techniques. 3D-CRT and VMAT led to comparable probabilities of carcinogenesis for structures adjacent to the target volume site [17]. Hypof fractionated treatment resulted in an increased bladder cancer risk compared to the therapeutic irradiation delivered with the typical fractions of 1.8 to 2 Gy [18]. The opposite effect was found for the development of soft tissue and bone sarcomas and solid tumors in the prostate, ovaries, and uterus [17]. The use of 10 MV instead of 6 MV photons for pelvic IMRT and VMAT led to comparable probabilities for developing secondary bowel malignancies and to small reductions in bladder cancer risk [18].