Optimal Prostate Cancer Radiation Dosage

Layth Alkhani
March 20, 2024

Submitted as coursework for PH241, Stanford University, Winter 2024

Fig. 1: Prostate cancer recurrence rates versus radiation dose, from Table 1. [2] (Image Source: L. Alkhani)

The management of prostate cancer through radiation therapy has evolved significantly, leveraging technological advancements to enhance treatment precision and patient outcomes. The dosage of radiation plays a crucial role in the efficacy and safety of the treatment, with studies emphasizing the importance of optimizing radiation doses to balance tumor control with the minimization of side effects.

One example of the technological advancements comes in the form of High-Dose Intensity-Modulated Radiation Therapy (IMRT) has emerged as a significant innovation. IMRT represents a sophisticated advancement in the precise delivery of radiation therapy, especially for complex cases like prostate cancer. Unlike traditional radiation therapy that emits uniform beams, IMRT uses advanced computer algorithms to modulate or vary the intensity of each radiation beam. [1] This modulation allows for the creation of radiation doses that are tailored to the three-dimensional shape of the tumor, achieving high precision in targeting cancerous cells. [1] The technology enables the delivery of radiation in a way that closely conforms to the shape of the tumor, minimizing exposure and damage to surrounding healthy tissues. [1] This precision is achieved through the use of computer-generated images to map the location and shape of the prostate tumor, allowing for targeted treatment. [1]

The physics of X-ray radiation plays a critical role in how IMRT is delivered. X-rays are penetrating by nature, meaning they can pass through various types of tissues before reaching the target tumor. When a beam of X-rays with a round cross-sectional profile is directed at the body, it creates an imaginary cylinder of irradiated tissue. [1] By irradiating from multiple directions and adjusting the intensity of each beam, IMRT ensures that these "cylinders" of radiation overlap precisely at the tumor location, delivering a higher dose to the tumor while sparing the surrounding healthy tissues. [1]

A study involving 772 patients treated with IMRT reported a dose range of 81.0 Gy in 90% of the patients and 86.4 Gy in 10% of the patients. [1] When discussing radiation doses, such as 81.0 Gy and 86.4 Gy, it's crucial to specify that these doses are localized to the tumor region within the prostate, not administered to the whole body. Radiation doses are measured in Gray (Gy), where one Gray represents the absorption of one joule of radiation energy per kilogram of tissue. The mentioned doses far exceed what would be safe if distributed throughout the entire body; instead, they are precisely targeted to maximize treatment efficacy while minimizing risk. This approach has demonstrated a reduction in both acute and late toxicities compared to conventional techniques, with early toxicity and biochemical outcomes appearing favorable. Specifically, the study reported minimal Grade 2 rectal toxicity and a low incidence of urinary symptoms, illustrating the potential of high-dose IMRT to improve patient quality of life through reduced treatment-related complications. [1]

Radiation Dose (Gy) Infield Recurrence Rate (%)
Stage B Stage C
< 60 24 25
60 - 65 13 28
65 - 70 13 23
> 70 14 17
Table 1: Prostate cancer recurrence rater versus radiation dosage for Stage B and Stage C patients. [2]

Analysis

The question of optimal dosage is further explored in Patterns of Care studies, which have analyzed outcomes across a broad spectrum of radiation doses. [2] These studies have indicated significant dose effects on local control of prostate cancer, particularly highlighting the need for dose optimization based on tumor stage. [2] For instance, Stage B cancers exhibit improved local control with doses ranging between 60 Gy and 70 Gy, suggesting that doses below 60 Gy increase the likelihood of local failure without demonstrating improvements in control for doses above 70 Gy. [2] Conversely, patients with Stage C cancer may require doses equal to or greater than 70 Gy for optimal local control, justifying potential increases in morbidity associated with these higher doses. [2]

This can be seen looking at Table 1 which shows recurrence versus radiation dose. [2] The recurrence rate shown in this table is a total of all infield recurrence rates taken for patients treated at a particular dosage within 7 years. For example, for stage C, < 60 out of the 69 patients treated at that particular dosage 17 had infield recurrence. [2] To understand the trend in outcomes, understanding the meaning of Stage and Infield Recurrence Rate is essentia. The "stage" of prostate cancer describes the extent of the disease, with higher stages indicating more advanced cancer (i.e. C is higher than B). "Infield recurrence rate" refers to the percentage of patients whose cancer returns within the area that was initially treated with radiation. This metric is crucial for assessing the effectiveness of the therapy.

This body of evidence underscores the nuanced approach required in determining the appropriate radiation dosage for treating prostate cancer. It reveals a complex interplay between the need to achieve effective tumor control and the imperative to minimize treatment-related side effects. High-dose IMRT emerges as a promising strategy that leverages advanced technology to target cancer cells more precisely, thereby offering a favorable risk-benefit ratio. As the field continues to evolve, further research will be crucial in refining these approaches, with the ultimate goal of personalizing treatment to achieve the best possible outcomes for patients with prostate cancer.

© Layth Alkhani. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.

References

[1] D. E. Spratt et al.,"Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer," Int. J. Radiat. Oncol. Biol. Phys. 85, 686 (2013).

[2] J. Zelefsky et al., "High Dose Radiation Delivered By Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer," J. Urol. 166, 876 (2001).