Second primary cancers after radiation for prostate cancer: A systematic review of the clinical data and impact of treatment technique

Abstract

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.

Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis

“…13 Historically, this has been defined as five years. 13 21-23 There were differences in the use and application of the length of the lag period from the time of treatment to diagnosis of secondary cancer among included studies.…”

“…9 10 One previous review concluded a negligible risk of secondary malignancies after radiotherapy, 11 whereas other reviews concluded that this is an important risk for both patients and physicians to consider. [12][13][14] A previous meta-analysis lacked data from several important recent publications. 15 While direct radiation carcinogenesis has long been accepted, 16 there is evidence that irradiation of the prostate might contribute to carcinogenesis outside the irradiated area through radiation scatter and radiation induced genetic alterations without direct exposure because of increased reactive oxygen species [17][18][19] and…”

Risk of second cancer following radiotherapy for prostate cancer: a population-based analysis

“…Radiation induced second cancers (RISC) are rare but relevant late effects of radiation therapy (RT) [1, 2]. In principle most of the knowledge regarding RISC is derived from epidemiological data of atomic bomb survivors, nuclear accidents and database analyses [3].…”

Risk of Second Cancers According to Radiation Therapy Technique and Modality in Prostate Cancer Survivors

“…Subsequent malignancies are an uncommon but serious and debilitating consequence of radiation therapy for the treatment of cancer (1). Among men who elect treatment for prostate cancer, nearly two-thirds of those who are older than 65 years of age receive some form of radiation therapy (RT), and one-third undergo surgery (2).…”