Emerging Modalities in Radiation Therapy for Prostate Cancer

Introduction

Radiation therapy techniques and their combination with other modalities have developed rapidly over the past two decades in radiation oncology. This continues today at an ever increasing pace offering considerable hope to the patients with both localized and metastatic disease. This chapter will attempt to highlight the following areas in the treatment of prostate cancer. The areas are better methods for the stratification of patients who would truly benefit from treatment, improved target definition using both anatomical and biological techniques, accelerated and more cost-effective treatments with greater accuracy, better combinatorial treatments involving systemic and surgical approaches, adaptive radiation therapy, and expansion of new types of external beam irradiation.

Identification of patients for radiation therapy

The role of radiation therapy in the treatment of prostate cancer is still evolving. One of the most important issues still is the identification of the patients that would most benefit from radiation therapy. By definition radiation therapy is used for local control. Several new tests have been designed to determine whether patients have systemic disease. Curative intent would only be in patients who have no evidence of distant metastatic disease. Multiple predictive tools have been developed to, first, determine patients’ risk for distant disease; second, reduce risks in cancer recurrence after prostatectomy and third, to increase the survival benefit. One of the predictive tools is the Cancer of the Prostate Risk Assessment Postsurgical Score (CAPRA-S). Recently, CAPRA-S was validated in a multi-institutional review to be able to predict disease recurrence and mortality after radical prostatectomy.

There are several new strategies being employed with magnetic resonance imaging (MRI) scans. Increasing data are supporting MRI and MR spectroscopic imaging (MRSI) as being superior to the trans-rectal ultrasound (TRUS) procedure in locating prostate tumors. In one study the accuracy of dynamic contrast enhanced MRI with three-dimensional MRSI was compared with trans-rectal ultrasound in localizing prostate tumors. In this study, 73.6% of the patients had nonpalpable disease (T1c) and 68.64% of the patients had organ-confined disease (pT2). MRI was significantly better at detecting malignancies in the midgland (52% vs. 41.1%, P = 0.0015) and in the transitional zone (40.1% vs. 24.3%, P < 0.0001). MRI had a higher sensitivity in larger (≥50 g) than smaller prostates (50.3% vs. 42.2%, P = 0.0017). A genomic test using the 3T multiparametric MRI – Blue Laser ^TM – could be used in identifying prostate cancer at its early stages. This genomic test works at the DNA level to identify Colton early stage prostate carcinoma. It identifies an epigenetic field or “halo” associated with malignancy at the DNA level in cells adjacent to the cancer foci. This test is still not commonly used but may help detect prostate cancer at the early stages when local treatment may be more effective.

Tests that measure multiple markers can help determine the risk for developing metastatic disease. One such test is the “Decipher” (developed by GenomeDx Biosciences) that measures 22 markers associated with aggressive prostate cancer. In one study, addition of “Decipher” test to the CAPRA-S and Stephenson nomogram, improved the accuracy of predicting metastatic disease within 5 years after surgery in an independent cohort of men with adverse pathologic features after radical prostatectomy. Decipher was independently validated as a genomic metastasis signature for predicting metastatic disease within 5 years after surgery in a cohort of high-risk men treated with radical prostatectomy without adjuvant therapy.

Another area with great promise is the biomarker discovery, which has been extensively investigated in recent years. We can hope for the availability of genomic, proteomic, as well as metabolomic biomarkers in the near future, which may be helpful in the stratification of patients who will or will not be benefited from a given radiation treatment.