After prostate cancer surgery, doctors often face a difficult decision. If tests suggest that cancer may return, should radiation treatment be used alone, or should hormone therapy be added as extra protection?
A large new analysis suggests that some familiar warning signs cannot answer that question as well as doctors might hope. The study, led by UCLA Health Jonsson Comprehensive Cancer Center researchers, was published in European Urology.
When the prostate is removed during cancer surgery, specialists carefully examine the tissue. They look for clues that show whether the tumor behaved aggressively or may have escaped beyond the prostate.
These clues are useful because prostate cancers are not all alike. Some remain limited to the prostate for years, while others can return after treatment and eventually spread to distant organs.
One important clue is the grade of the cancer. A high-grade tumor has cells that look very abnormal and generally behaves more aggressively than a lower-grade tumor.
Doctors also check whether cancer has grown outside the prostate or entered the seminal vesicles, small glands located behind the prostate. Another warning sign is a positive surgical margin, meaning cancer cells are present at the edge of tissue removed during surgery.
All of these findings can help estimate the chance of future problems. But predicting that a person is at high risk is different from knowing whether a particular additional treatment will improve that person’s outcome.
The new study focused on this difference. Researchers asked whether patients with a larger number of unfavorable findings would receive more benefit from adding hormone therapy to radiation after surgery.
Hormone therapy is used because many prostate cancers are driven by male hormones called androgens. Reducing these hormones or blocking their action can slow the growth of prostate cancer cells and make treatment more effective in some situations.
But suppressing hormones can affect the rest of the body as well. Patients may experience hot flashes, low energy, reduced sexual function, loss of muscle or bone, and changes that affect weight and metabolism.
For that reason, doctors would like a reliable way to identify the people for whom the extra treatment is truly worthwhile. Giving more treatment is not automatically better if the added therapy brings side effects without a meaningful improvement in survival.
The research team analyzed information from 4,781 patients enrolled in five phase 3 randomized trials. All had undergone prostate cancer surgery and later received radiation treatment, with trial participants receiving either radiation alone or radiation plus hormone therapy.
The researchers created a simple count based on four concerning findings: Grade Group 4 or 5 disease, spread into the seminal vesicles, growth outside the prostate and positive surgical margins. Each patient received a score between zero and four.
As expected, the score worked as a measure of prognosis. People with more adverse features had a greater risk of death and of their cancer spreading to distant parts of the body.
However, the score did not work as a guide to hormone therapy benefit. Patients with more warning signs did not receive a clearly larger survival advantage from hormone therapy than patients with fewer warning signs.
This remained true even for patients with several aggressive features. In other words, a cancer could look more dangerous under the microscope without being more sensitive to the added hormone treatment.
The researchers also examined patients whose PSA was no higher than 0.5 ng/mL before radiation. PSA, or prostate-specific antigen, is measured with a blood test and is commonly used to follow patients after prostate cancer treatment.
The findings in this lower-PSA group followed the same pattern. The number of adverse tissue features still did not clearly identify who gained more from adding hormone therapy.
Dr. Amar Kishan, who led the research, said the results highlight the difference between a marker that predicts a patient’s future risk and one that predicts response to treatment. That distinction is central to the growing goal of personalized cancer care.
A risk marker answers a question such as, “How likely is this cancer to return or spread?” A treatment-response marker must answer a different question: “Is this particular therapy more likely to help this patient?”
Traditional pathology appears to do the first job better than the second in this setting. Researchers therefore believe molecular information from the tumor may be needed to guide treatment more precisely.
Future biomarkers might measure genes, proteins or other biological features that reveal what drives an individual tumor. If validated in strong clinical studies, such tests could help doctors separate patients who need additional treatment from those who can safely avoid it.
The current study is strengthened by its use of patient-level information from five randomized clinical trials and by its large sample. These data provide a strong foundation for examining whether the effect of treatment changes across groups with different pathological risks.
Still, the analysis does not establish that pathology has no role in treatment decisions, nor does it say that hormone therapy should be avoided. Pathology remains important for understanding cancer risk, and treatment must be chosen using the full clinical picture.
The study also cannot by itself tell doctors which new molecular test should replace or supplement existing information. Biomarkers will need independent testing and evidence that using them to guide treatment actually improves patient care.
The main lesson is therefore subtle but important. A person who has more aggressive cancer features is at greater risk, but greater risk does not automatically mean that the person receives greater benefit from every additional treatment.
That finding could eventually help make prostate cancer care more selective. If researchers can identify biological markers that truly predict hormone therapy response, patients may receive treatment based not only on how threatening their cancer appears, but also on how likely that cancer is to respond.
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Source: UCLA Health.
