The primary management of genitourologic malignant diseases has been tied to the use of radiation for more than 100 years. In 1895, 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 (Pasteau and Degrais, 1914). Radiotherapy became a mainstay of treatment for bladder and testicular cancers and later prostate cancer as supervoltage sources became available. Although chemotherapy and aggressive surgery have supplanted some of the uses of radiotherapy, radiation continues to play a major role in the management of carcinomas of the penis, urethra, prostate, and bladder. In this chapter, we review general principles and the indications for using radiation as a component in the primary management of urologic malignant diseases. The role of radiation as an agent of palliation has been well documented elsewhere and is excluded from this chapter.
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. Excited electron species generated in the presence of oxygen form peroxide radicals, which fix chemical lesions and result in the generation of either repairable or nonrepairable DNA double-strand breaks. High linear energy transfer radiation (including neutrons and heavy-charged particles) is associated with less repairable DNA damage. Classically, the expression of radiation damage is not seen until the target cells enter mitosis. Differentiated normal tissues with low mitotic activity, such as the heart and spinal cord, tend to express the effects of radiation much later than cells from more kinetically active tissues, such as the epithelial cells lining the rectum, bladder, or urethra. However, differentiated normal tissues with low mitotic activity are more sensitive to the use of high dose per fraction or high linear energy transfer radiotherapy. In organs in which the functional stromal cells are postmitotic, such as muscle cells and neurons, the damage is expressed by slowly dividing support cells such as endothelial cells.
In addition to the classic mechanism described earlier, radiation has been shown to induce programed cell death (apoptosis). Androgen-independent human prostate cancer cells activate a genetic program of apoptotic cell death in response to exposure to ionizing radiation, in a dose-dependent fashion (Sklar, 1993). Results from animal models suggest that it is better to achieve maximal androgen suppression before starting radiation treatment however, in humans this may be sequence and volume dependent as well (Roach M, 2012; Zietman, 2000).
Radiation Sensitivity and Tolerance
Radiation tolerance levels have been determined for nearby normal tissues that are likely to be affected during conventional fractionated radiotherapy treatment of tumors arising from the urinary tract. The term conventional fractionation generally refers to the delivery of a single daily dose of 180 cGy (1.8 Gy) to 200 cGy (2.0 Gy). When used alone, cumulative doses ...