CD105-assessed microvessel density and recurrence and progression in non-muscle- invasive bladder cancer: a retrospective cohort study
This retrospective cohort study of 157 patients with non-muscle-invasive bladder cancer concludes that CD105-assessed microvessel density does not predict recurrence and offers no incremental value over clinical risk factors, while its association with progression appears indistinguishable from tumor grade due to limited event numbers.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
Bladder cancer often begins as a growth that stays on the inner lining of the bladder, a stage doctors call non-muscle-invasive. While these early tumors can be removed with a scope, they have a stubborn habit of returning, and in some cases, they grow deeper and become more dangerous. To manage this, doctors rely on standard clues found in the tissue under a microscope, such as how fast the cells are dividing or how many separate tumors are present. However, these clues are not perfect, and researchers have long searched for a more reliable way to predict which patients will face a recurrence or a worsening of their disease. One promising avenue has been the study of angiogenesis, the process by which tumors build their own network of tiny blood vessels to feed themselves. A specific protein called CD105, found on the surface of cells that are actively building these new vessels, has been proposed as a marker to measure this activity. If a tumor has a high density of these active vessels, it might be a sign that the cancer is aggressive and likely to return or spread.
A team of researchers set out to test this idea in a large group of patients who had just undergone surgery to remove their early-stage bladder tumors. They gathered tissue samples from 157 consecutive patients treated between 2007 and 2011. The scientists focused specifically on the initial surgery specimens, looking for the presence of CD105 to count how many active blood vessels were present in the hottest spots of the tumor. They then followed these patients for an average of two years to see who experienced a return of the cancer and who saw their disease advance to a more serious stage. The goal was to see if the number of these active vessels could act as an early warning system, telling doctors which patients needed closer monitoring or more aggressive treatment.
The results offered a clear, if somewhat disappointing, answer regarding the return of the cancer. The researchers found that the number of active blood vessels had no connection to whether a patient's cancer would come back. Whether a patient had a low count of these vessels or a very high count, the likelihood of the tumor reappearing remained the same. The data showed that the standard factors doctors already use, such as the number of tumors and the type of treatment given, were far better at predicting recurrence than the blood vessel count. In fact, the study was large enough to be quite certain that this specific marker does not help in forecasting a return of the disease.
The story was slightly different when looking at the progression of the cancer, which means the tumor growing deeper into the bladder wall. Here, the researchers did find a pattern: patients whose tumors had a high number of active blood vessels were more likely to see their disease worsen. Specifically, no patient with a low count of these vessels experienced progression. However, when the researchers adjusted their analysis to account for the grade of the tumor—essentially how abnormal and aggressive the cells looked under a microscope—the power of the blood vessel count disappeared. It turned out that the tumors with the most active blood vessels were simply the ones that were already known to be high-grade and dangerous. The blood vessel count was not providing new information; it was just reflecting what the doctors could already see by looking at the cells themselves.
Ultimately, this study suggests that measuring the density of these specific blood vessels in the initial surgery specimen is not a useful tool for predicting which early bladder cancers will return. While the count of active vessels rises with the severity of the tumor, it does not offer an independent advantage over the standard grading of the cells. The findings indicate that the biological process of building new blood vessels is a downstream effect of the tumor becoming more aggressive, rather than a separate driver that can be measured to predict the future. For now, the search for a better predictor continues, but this particular marker appears to be a reflection of the disease's current state rather than a crystal ball for its future.
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