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Prostate Cancer: Combined Biopsy Strategy Makes for More Accurate Diagnosis

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Last year, nearly 175,000 American men were diagnosed with prostate cancer [1]. Most got the bad news after a blood test or physical exam raised concerns that warranted a biopsy of the prostate, a walnut-sized gland just below the bladder.

Traditional biopsies sample tissue from 12 systematically placed points within the prostate that are blind to tumor locations. Such procedures have helped to save many lives, but are prone to missing or misclassifying prostate cancers, which has led doctors both to over and under treat their patients.

Now, there may be a better approach. In a study of more than 2,000 men, NIH researchers and their colleagues recently found that combining the 12-point biopsy with magnetic resonance imaging (MRI)-targeted biopsy during the same session more accurately diagnoses prostate cancer than either technique alone [2].

The findings address a long-standing challenge in prostate cancer diagnostics: performing a thorough prostate biopsy to allow a pathologist to characterize as accurately as possible the behavior of a tumor. Some prostate tumors are small, slow growing, and can be monitored closely without treatment. Other tumors are aggressive and can grow rapidly, requiring immediate intervention with hormonal therapy, radiation, or surgery.

But performing a thorough prostate biopsy can run into technical difficulties. The 12-point biopsy blindly samples tissue from across the prostate gland, but it can miss a cancer by not probing in the right places.

Several years ago, researchers at the NIH Clinical Center, Bethesda, MD, envisioned a solution. They’d use specially designed MRI images of a man’s prostate to guide the biopsy needle to areas in the prostate that look suspicious and deserve a closer look under a microscope.

Through a cooperative research-and-development agreement, NIH and the now- Florida-based Philips Healthcare created an office-based, outpatient prostate biopsy device, called UroNav, that was later approved by the Food and Drug Administration. The UroNav system relies on software that overlays MRI images highlighting suspicious areas onto real-time ultrasound images of the prostate that are traditionally used to guide biopsy procedures.

The new technology led to a large clinical study led by Peter Pinto, a researcher with NIH’s National Cancer Institute. The study results, published in 2015, found that the MRI-targeted approach was indeed superior to the 12-point biopsy at detecting aggressive prostate cancers [3].

But some doctors had questions about how best to implement the UroNav system and whether it could replace the 12-point biopsy. The uncertainty led to a second clinical study to nail down more answers, and the results were just published in The New England Journal of Medicine.

The research team enrolled 2,103 men who had visible prostate abnormalities on an MRI. Once in the study, each man underwent both the 12-point blind biopsy and the MRI-targeted approach—all in a single office visit. Based on this two-step approach, 1,312 people were diagnosed with prostate cancer. Of that total, 404 men had evidence of aggressive cancer, and had their prostates surgically removed.

The researchers then compared the diagnoses from each approach alone versus the two combined. The data showed that the combined biopsy found 208 cancers that the standard 12-point biopsy alone would have missed. Adding the MRI-targeted biopsy also helped doctors find and sample the more aggressive cancers. This allowed them to upgrade the diagnosis of 458 cancers to aggressive and in need of more full treatment.

Combining the two approaches also led to more accurate diagnoses. By carefully analyzing the 404 removed prostates and comparing them to the biopsy results, the researchers found the 12-point biopsy missed the most aggressive cancers about 40 percent of the time. But the MRI-targeted approach alone missed it about 30 percent of the time. Combined, they did much better, underestimating the severity of less than 15 percent of the cancers.

Even better, the combined biopsy missed only 3.5 percent of the most aggressive tumors. That’s compared to misses of about 17 percent for the most-aggressive cancers for the 12-point biopsy alone and about 9 percent for MRI-targeted biopsy alone.

It may take time for doctors to change how they detect prostate cancer in their practices. But the findings show that combining both approaches will significantly improve the accuracy of diagnosing prostate cancer. This will, in turn, help to reduce risk of suboptimal treatment (too much or too little) by allowing doctors and patients to feel more confident in the biopsy results. That should come as good news now and in the future for the families and friends of men who will need an accurate prostate biopsy to make informed treatment decisions.

References:

[1] Cancer State Facts: Prostate Cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program.

[2] MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. Ahdoot M, Wilbur AR, Reese SE, Lebastchi AH, Mehralivand S, Gomella PT, Bloom J, Gurram S, Siddiqui M, Pinsky P, Parnes H, Linehan WM, Merino M, Choyke PL, Shih JH, Turkbey B, Wood BJ, Pinto PA. N Engl J Med. 2020 Mar 5;382(10):917-928.

[3] Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Siddiqui M, Rais-Bahrami, George AK, Rothwax J, Shakir N, Okoro C, Raskolnikov D, Parnes HL, Linehan WM, Merino MJ, Simon RM, Choyke PL, Wood BJ, and Pinto PA. JAMA. 2015 January 27;313(4):390-397.

Links:

Prostate Cancer (National Cancer Institute/NIH)

Video: MRI-Targeted Prostate Biopsy (YouTube)

Pinto Lab (National Cancer Institute/NIH)

NIH Support: National Cancer Institute; NIH Clinical Center


Different Cancers Can Share Genetic Signatures

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Cancer types floating over a cell with unraveling DNA

NIH-funded researchers analyzed the DNA of these cancers.

Cancer is a disease of the genome. It arises when genes involved in promoting or suppressing cell growth sustain mutations that disturb the normal stop and go signals.  There are more than 100 different types of cancer, most of which derive their names and current treatment based on their tissue of origin—breast, colon, or brain, for example. But because of advances in DNA sequencing and analysis, that soon may be about to change.

Using data generated through The Cancer Genome Atlas, NIH-funded researchers recently compared the genomic fingerprints of tumor samples from nearly 3,300 patients with 12 types of cancer: acute myeloid leukemia, bladder, brain (glioblastoma multiforme), breast, colon, endometrial, head and neck, kidney, lung (adenocarcinoma and squamous cell carcinoma), ovarian, and rectal. Confirming but greatly extending what smaller studies have shown, the researchers discovered that even when cancers originate from vastly different tissues, they can show similar features at the DNA level


Personalized Cancer Vaccine Enters Human Trials

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Photo of a researcher looking at a silver disc held by a curved hemostat

Caption: The new melanoma vaccine, which is implanted beneath the skin, is now being tested in human trials.
Credit: Wyss Institute and Amos Chan

This aspirin-sized disk is the first therapeutic cancer vaccine implanted beneath the skin [1]. We know it can eradicate melanoma in mice—the deadliest form of skin cancer—with impressive efficacy [2]. Now, it’s being tested in human trials.


New Understanding of a Common Kidney Cancer

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Purple stained kidney tissue

Caption: Histologic image of clear cell kidney cancer
Slide courtesy of W. Marston Linehan, National Cancer Institute, NIH

Understanding how cancer cells shift into high gear—what makes them become more aggressive and unresponsive to treatment—is a key concern of cancer researchers. A new study reveals how this escalation occurs in the most common form of kidney cancer: clear cell renal cell carcinoma (ccRCC). The study shows that ccRCC tumors acquire specific mutations that encourage uncontrollable growth and shifts in energy use and production [1].

Conducted by researchers in the NIH-led The Cancer Genome Atlas (TCGA) Research Network, the study compared more than 400 ccRCC tumors from individual patients with healthy tissue samples from the same patients. Researchers were looking for differences in the gene activity and proteins in healthy vs. tumor tissue.