Radiation has played an important role in the primary management of genitourologic malignancies for more than 100 years. In 1895, Wilhelm Roentgen described x-rays; by 1899, a patient with skin cancer was cured with radiation; and within 10 years, radiation was used to treat prostate cancer. Radiotherapy has become a mainstay of treatment for cancers arising from the bladder and testes and prostate and to a lesser degree of penile, urethral, and kidney cancers as megavoltage sources became available, despite advances in chemotherapy and aggressive surgery. Moreover, the advent of dose-escalated, short-course radiation therapy such as stereotactic body radiation (SBRT), has opened new avenues for the use of radiation in the treatment of genitourinary malignancies (Gonzalez-Motta and Roach, 2017; Kishan et al, 2019a; Morgan et al, 2018). In this chapter, we review general principles and the indications for using radiation as a component in the primary management of urologic malignant diseases. Although radiation also plays a major role as an agent of palliation, this information has been well documented elsewhere and is excluded from this chapter (Hansen and Roach, 2018; Bourgeois 3rd et al, 2011; Carl et al, 2019).
GENERAL PRINCIPLES OF RADIOTHERAPY
Mechanisms of Cytotoxicity
The effects of radiation on tumor and surrounding normal tissues are thought to be mediated primarily through the induction of unrepaired double-strand breaks in DNA (McMahon and Prise, 2019; Tang et al, 2019). This can be attributed to the direct impact to the DNA strand but more frequently may be due to the secondary effect of excited electron species generated in the presence of oxygen from peroxide radicals. These unstable scavenger molecules then interact with nucleotide bases, and the consequent damage to the DNA may lead to the generation of either repairable or nonrepairable DNA double-strand breaks during mitotic division. High-linear-energy-transfer radiation (including neutrons, protons, carbon, and other heavy-charge particles) is associated with greater biological effect because of its ability to induce direct, physical double-strand breaks. However, as the vast majority of DNA in a cell is not being actively transcribed, the cytotoxic impact of radiation may not be observed until the radiated cells enter mitosis. Postmitotic normal tissues with low mitotic activity, such as the heart, brain, and spinal cord, tend to express the effects of radiation much later than do cells from actively dividing tissues, such as the epithelial cells lining the rectum, bladder, or urethra. This process leads to apoptosis of cells with irreparable DNA damage and enables tissue regeneration by mitosis. However, cells in postmitotic normal tissues with low mitotic activity are more sensitive to the use of high-dose-per-fraction or high-linear-energy-transfer radiotherapy because fewer cells turn over, and therefore accumulated DNA damage may not result in cell death and elimination of cells that then would have abnormal genetic material (Allen et al, 2015). In organs in which the functional stromal cells are postmitotic, such as muscle cells and ...