In an exciting breakthrough, researchers at the UCLA Health Jonsson Comprehensive Cancer Center have successfully validated a groundbreaking test that can identify which prostate cancer patients are at risk of developing prolonged urinary side effects following radiation therapy.

The newly developed test, named PROSTOX, stands as the first of its kind to utilize microRNAs for determining the potential toxicity of cancer treatments. This innovation holds the promise of alleviating the long-term complications associated with radiation therapy by pinpointing high-risk patients before they initiate treatment.

In a recent study published in the esteemed journal Clinical Cancer Research, the UCLA team confirmed PROSTOX's capability to predict enduring urinary side effects. These side effects can manifest as urinary tract pain, blood in the urine, frequent urges to urinate, and issues such as leakage. The findings also revealed that varying genetic factors could be tied to specific types of side effects, underscoring the necessity for a more tailored approach in cancer treatment.

Dr. Joanne Weidhaas, a key researcher and professor at the David Geffen School of Medicine at UCLA, emphasized the significance of this test, stating, "We’ve always known that some men experience life-altering side effects post-treatment, but until now, we had no means to predict who would suffer from them. PROSTOX uniquely examines a patient’s genetics to assess their individual risk of radiation-induced side effects, which aids in guiding treatment decisions to minimize toxic effects."

For many men diagnosed with early-stage prostate cancer, treatment typically involves stereotactic body radiotherapy (SBRT), a highly accurate radiation therapy delivered over five sessions rather than the traditional weeks-long regime. While effective, SBRT is not without side effects. Though major complications are rare, some patients can experience moderate toxicity that seriously impacts their quality of life—leading to a pressing need for preventive measures.

Patients often face disruptive urinary side effects post-radiation, presenting itself in various forms: acute toxicity appears soon after treatment, while chronic toxicity can endure long after, impacting daily routines. This unpredictability has made it challenging for healthcare providers to prepare patients for potential difficulties.

In earlier research, Dr. Weidhaas and her team found that specific inherited genetic variations, particularly in relation to microRNAs that govern gene expression, could forecast the likelihood of experiencing these side effects. Working in tandem with MiraDx, they crafted the PROSTOX test, highlighting 32 unique mirSNPs associated with radiation-related complications. Their research indicated that individuals categorized as high-risk are approximately 10 to 12 times more likely to confront serious long-term urinary problems.

The recent study involved a rigorous validation of PROSTOX on a cohort of 148 prostate cancer patients undergoing MRI- or CT-guided SBRT as part of the MIRAGE phase III clinical trial. Remarkably, the test proved its efficacy in predicting significant long-term urinary toxicity, irrespective of the imaging technique used. It was also found to be unaffected by age or radiation dose, highlighting its role as an independent measure of genetic susceptibility to toxicity.

Moreover, the study differentiated between chronic and late toxicity related to radiation, uncovering distinct genetic signatures for each type. Late toxicity was linked to immune system dysfunction and prolonged inflammation, while chronic toxicity may be mitigated through advancements in radiation technology, suggesting that improved techniques could alleviate these side effects.

Dr. Amar Kishan, who led the study, pointed out the complexities in comparing radiation toxicity across different treatment eras, but confidently stated, "This research affirms PROSTOX as a reliable predictive biomarker for toxicity, independent of the advancements made in radiation therapy. It identifies the safest treatment pathways for patients, aiming to reduce toxicity."

Looking ahead, the research team stresses the vital need to integrate genetic testing with modern radiation therapies to further tailor treatments for prostate cancer patients, thereby diminishing the risks associated with serious genitourinary (GU) side effects.

Co-author Dr. Michael Steinberg stated, "This type of genetic testing, when aligned with advanced radiation therapies, allows for a customized treatment approach, equipping patients and doctors alike with crucial insights for making the safest possible treatment choices."

The team plans to extend the validation of PROSTOX across larger patient populations and are investigating similar genetic biomarkers that could predict side effects in various cancers treated with radiation or immunotherapy.

In closing, Dr. Weidhaas shared her aspirations: "With continued research, we aim to implement these genetic findings throughout cancer care. Our ultimate goal is for patients to not only survive cancer but also thrive following treatment."

This pioneering study, supported by grants from the National Cancer Institute, heralds a new era in personalized cancer treatment, placing the power of precision in the hands of patients and doctors.