Doctors can learn a great deal about prostate cancer by examining the prostate after surgery.
A new study, however, shows that signs of an aggressive tumor may not tell doctors which patients will gain the most from adding hormone therapy to radiation treatment.
The research was led by investigators at the UCLA Health Jonsson Comprehensive Cancer Center. The findings were published in European Urology.
Prostate cancer is one of the most common cancers in men. Many tumors grow slowly, but others are more aggressive and have a greater chance of returning or spreading to other parts of the body.
For some patients, surgery is used to remove the prostate. Doctors then examine the removed tissue under a microscope to learn more about the cancer and estimate the risk that some cancer cells may remain.
Radiation therapy may be recommended after surgery when there is concern that the cancer could return. Radiation uses high-energy beams to damage cancer cells that may still be present around the area where the prostate was removed.
Doctors sometimes add hormone therapy to this radiation. Prostate cancer cells often depend on male hormones, especially testosterone, to grow, so hormone treatment lowers these hormones or blocks their effects.
This combination can improve outcomes for some patients, but hormone therapy has drawbacks. It can cause hot flashes, tiredness, sexual problems, loss of bone strength and changes in metabolism, among other side effects.
That creates an important treatment question. Doctors want to give hormone therapy to patients who are likely to benefit while avoiding unnecessary treatment in people who are unlikely to gain much from it.
Traditionally, doctors have used features seen in the removed prostate tissue to judge how dangerous a cancer may be. The UCLA-led team wanted to know whether those same features could also predict who benefits most from hormone therapy.
The researchers combined individual patient information from five phase 3 randomized clinical trials. These types of trials are considered especially valuable because patients are assigned to different treatment approaches so researchers can compare outcomes.
The analysis included 4,781 people who had prostate cancer surgery and later received radiation. Some received radiation alone, while others received radiation together with hormone therapy.
The researchers focused on four unfavorable findings in the surgical tissue. These included very high-grade cancer, cancer that had reached the seminal vesicles, cancer that had grown outside the prostate and cancer cells found at the edge of the removed tissue.
Rather than considering each sign separately, the team gave patients a score from zero to four according to how many of these features were present. A higher number therefore represented a greater collection of traditional warning signs.
The results confirmed something doctors already expected. Patients with more unfavorable features generally had poorer outcomes, including a higher risk of dying or having their cancer spread elsewhere in the body.
But the second finding was more surprising. Having more of these high-risk features did not mean that a patient received a larger benefit from adding hormone therapy to radiation.
Even people whose tumors had several concerning features did not show a clearly greater improvement in overall survival or survival without distant cancer spread from hormone therapy than people with fewer such features.
The same general pattern was seen among patients whose PSA level was 0.5 ng/mL or lower before radiation. PSA is a protein made by prostate cells, and doctors commonly measure it in the blood to help monitor prostate cancer.
Lead author Dr. Amar Kishan of UCLA said the findings show an important difference between estimating risk and predicting treatment response. A feature can tell doctors that a cancer is dangerous without necessarily revealing which treatment will work best against it.
This distinction matters because medical decisions have often relied heavily on clinical and pathological risk. The new analysis suggests that simply adding together traditional warning signs may not be precise enough to decide who should receive additional hormone treatment.
The researchers argue that better biological markers are needed. Such markers could include measurable molecular features of a tumor that reveal how its cancer cells work and how likely they are to respond to a particular treatment.
The study has important strengths, including its large number of patients and the use of data from five randomized phase 3 trials. Combining individual patient data also allowed the researchers to examine treatment effects more carefully than would be possible from a small single study.
However, the findings do not mean hormone therapy is useless after prostate cancer surgery. The analysis asks a narrower question: whether the number of these four traditional pathological warning signs can identify people who receive greater benefit from adding hormone therapy.
Treatment decisions still depend on many factors, including PSA levels, timing of radiation, a person’s general health, cancer characteristics and the expected advantages and side effects of treatment. Patients should not use the study to change therapy without discussing their individual situation with their cancer team.
Overall, the study challenges the idea that the most aggressive-looking cancers automatically gain the most from extra hormone treatment. Pathology remains valuable for estimating prognosis, but a different type of information may be needed to predict treatment benefit.
The next step is to find and validate biomarkers that can make that distinction. If researchers succeed, doctors may eventually be able to offer hormone therapy more selectively, protecting patients who need it while sparing others from side effects that bring little additional benefit.
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