The development of a radiation induced second primary cancer (SPC) is one the most serious long term consequences of successful cancer treatment. This review aims to evaluate SPC in prostate cancer (PCa) patients treated with radiotherapy, and assess whether radiation technique influences SPC. A systematic review of the literature was performed to identify studies examining SPC in irradiated PCa patients. This identified 19 registry publications, 21 institutional series and 7 other studies. There is marked heterogeneity in published studies. An increased risk of radiation-induced SPC has been identified in several studies, particularly those with longer durations of follow-up. The risk of radiation-induced SPC appears small, in the range of 1 in 220 to 1 in 290 over all durations of follow-up, and may increase to 1 in 70 for patients followed up for more than 10 years, based on studies which include patients treated with older radiation techniques (i.e. non-conformal, large field). To date there are insufficient clinical data to draw firm conclusions about the impact of more modern techniques such as IMRT and brachytherapy on SPC risk, although limited evidence is encouraging. In conclusion, despite heterogeneity between studies, an increased risk of SPC following radiation for PCa has been identified in several studies, and this risk appears to increase over time. This must be borne in mind when considering which patients to irradiate and which techniques to employ.

Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute risks are very low, large relative risks become less meaningful. A calculated relative radiation-induced second cancer risk benefit from SABR and FFF techniques was theoretically predicted, although absolute radiation-induced second cancer risks were low for all techniques, and absolute differences between techniques were small.

Stereotactic Body Radiation Therapy (SBRT) is an emerging effective treatment for hepatocellular carcinoma (HCC) associated with acceptable rates of toxicity in appropriately selected patients. Despite often being reserved for patients unsuitable for other local treatments, prospective and retrospective studies have demonstrated excellent long-term control. SBRT may be used as a stand-alone treatment, or as an adjunct to other HCC therapies. Based on available data, SBRT appears to complement existing local liver therapies. Randomized and nonrandomized comparative studies are required to better determine the optimal role of SBRT in HCC treatment.