PROMIS to Compare mp-MRI With TRUS-Guided Biopsy

Becky McCall

March 15, 2012

March 15, 2012 (Paris, France) — It soon might be possible to detect clinically significant prostate cancer and rule out insignificant prostate cancer using multiparametric (mp) magnetic resonance imaging (MRI). The Prostate MR Imaging Study (PROMIS) will compare results from mp-MRI with those from transrectal ultrasound (TRUS)-guided biopsy and template prostate mapping (TPM).

Hashim Ahmed, MD, Medical Research Council clinician scientist in urology at University College London, United Kingdom, described the PROMIS study design and objectives here at the European Association of Urology (EAU) 27th Annual Congress.

PROMIS is a multicenter, prospective, validation, paired cohort study designed to compare the detection rate of clinically significant prostate cancer between the mp-MRI-based diagnostic pathway and TRUS-guided biopsy plus TPM, which biopsies the prostate every 5 mm. In addition, PROMIS will evaluate whether mp-MRI can identify men with no cancer or clinically insignificant disease.

Dr. Ahmed explained that the overdiagnosis of prostate cancer is currently a major problem. When men are found to have an elevated prostate-specific antigen (PSA) level, they undergo a 12-core biopsy of the prostate. "This biopsy is blind to the location of the cancer and is conducted in the hope that you will hit the cancer," he said.

Every year, about a million TRUS-guided biopsies in Europe and a million in the United States are performed. According to Dr. Ahmed, there is a significant sepsis rate (2% to 4%, although recent data have shown it to be as high as 6%) associated with TRUS-guided biopsy.

Dr. Ahmed and his colleagues plan to recruit approximately 700 men with an elevated PSA level to undergo mp-MRI, followed by a combination of TRUS-guided biopsy and TPM. TPM will be used as a reference test to determine the value of mp-MRI in prostate cancer diagnosis.

"Most men who have had a previous biopsy prefer template biopsies, which go through the skin rather than the contaminated rectum. In the few hundred cases that we've done, there has been no sepsis, so it's a clean procedure," Dr. Ahmed noted. "It's also very accurate. It allows us to detect and rule out clinically significant disease with about 95% negative predictive value and 90% to 95% sensitivity."

To prevent bias, patients and investigators will be blind to the results until each of the 3 tests have been assessed independently and recorded.

The researchers will also examine biomarkers in the blood and urine of study participants, Dr. Ahmed explained. He hopes that PROMIS will validate existing and discover new biomarkers. "We may find a blood or urine test that is more cost effective than mp-MRI."

PROMIS received approval based in part on a recent smaller study, also conducted by Dr. Ahmed and colleagues and also presented at the EAU meeting.

In that pilot study, mp-MRI was found to have a negative predictive value of 95% for clinically important disease, defined as a Gleason score of at least 4 and/or a cancer core length of at least 6 mm. Dr. Ahmed explained that mp-MRI is negative or normal in about 1 of 4 men with an elevated PSA level.

This finding means that if 1000 men with an elevated PSA level have an mp-MRI before biopsy, biopsy can be avoided in 250, said Dr. Ahmed. "Of these 250 men, 238 would have no cancer or no clinically significant cancer."

In the pilot study, the researchers recruited 64 men with no cancer or with low- to intermediate-risk prostate cancer diagnosed using TRUS-guided biopsy. Mean age was 62 years, mean PSA level was 8.2 ug/L, and 50% of biopsy sectors showed cancer (67% with a Gleason score of 3 or less).

All subjects received mp-MRI followed by TPM. When the mp-MRI and TPM results were compared, "consistent negative predictive values for clinically significant cancer" were found. In other words, if the mp-MRI was negative, it was unlikely the patient had clinically important disease in the prostate, Dr. Ahmed explained.

From this pilot study, the researchers concluded that mp-MRI seems to have the ideal attributes of a triage diagnostic test for identifying men who can avoid a prostate biopsy. These findings led to the PROMIS study.

"We think this [technique] has promise; the key challenge now is reproducibility.... We need to make sure everyone is trained to the same standard and that the MRIs are conducted to the same standard. This is a key part of PROMIS."

In an interview with Medscape Medical News, Arnauld Villiers, MD, from the urology service at Hôpital Claude Huriez in Lille, France, said the study is ambitious but feasible.

The current TRUS-guided approach to diagnosis, in which men are judged to be at risk on the basis of elevated PSA levels and other risk factors, results in unwanted outcomes. "Most biopsies are negative, but are accompanied by discomfort and significant rates of side effects, particularly urosepsis." Dr. Villiers explained.

He added that there is a pressing need for new methods of diagnosis. "About half of patients are diagnosed with clinically insignificant disease. About 25% of these patients harbor higher-risk disease that is missed or poorly sampled on the original biopsy. It is therefore urgent to consider the role of MRI before biopsy."

The hope of PROMIS is that, in a patient with an elevated PSA level, mp-MRI will identify whether there is a significant tumor, where it is located, and how aggressive it is. "Also, it will prove that with a negative MRI, there is no significant cancer," said Jelle Barentsz, MD, professor of radiology at Radboud University, Nijmegen Medical Centre, the Netherlands.

"Promotion of the importance of PROMIS is essential for its success. I am afraid that patient recruitment will be low because of the invasiveness of the methodology," Dr. Barentsz said. Patients will undergo template saturation biopsy (more than 48 cores) under anesthesia.

This study received funding the National Institute for Health Research health technology assessment program, the Prostate Cancer Charity, and the Medical Research Council. Dr. Ahmed and Dr. Villiers have disclosed no relevant financial relationships. Dr. Barentsz reports receiving support from Galil Medical.

European Association of Urology (EAU) 27th Annual Congress: Abstracts 824 and 795. Presented February 27, 2012.

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