STHLM3 test may be superior to PSA for detection of aggressive prostate cancer

A novel prostate cancer testing method can identify aggressive forms of the cancer earlier than PSA testing, according to results of a prospective population-based study.

The Stockholm 3 (STHLM3) blood test also reduced the number of false positives, thereby minimizing unnecessary biopsies.

“PSA can’t distinguish between aggressive and benign cancer,” Henrik Grönberg, MD, PhD, professor of cancer epidemiology at Karolinska Institutet in Stockholm, said in a press release. “Today, men who don’t have cancer or who have a form of cancer that doesn’t need treating must go through an unnecessary, painful and sometimes dangerous course of treatment. On top of this, PSA misses many aggressive cancers. We, therefore, decided to develop a more precise test that could potentially replace PSA.”

STHLM3 analyzes six protein markers, more than 200 genetic markers, and other variables such as age, family history and previous biopsies of the prostate. Additionally, a digital rectal exam and prostate volume test are performed.

Grönberg and colleagues used the Swedish Population Register to identify men aged 50 to 69 with prostate cancer and invited them to participate in the trial. Each study participant received both PSA and STHLM3 testing.

The training cohort included 11,130 men enrolled between May 2012 and May 2013. A validation cohort included 47,688 men enrolled between August 2013 and December 2014.

The researchers found that the STHLM3 performed better than PSA for detection of cancers with a Gleason score of 7 or higher (P < .0001; PSA area under the curve [AUC] = 0.56; 95% CI, 0.55-0.6; STHLM3 AUC = 0.74; 95% CI, 0.72-0.75).

Results of a multiple logistic regression model showed all variables used in the STHLM3 model were significantly associated with prostate cancers of Gleason 7 or higher (P < .05).

Using the PSA sensitivity cutoff of 3 ng/mL or greater to diagnose high-risk prostate cancer, the researchers determined use of STHLM3 could reduce the number of biopsies by 32% (95% CI, 24-39) and could avoid 44% (95% CI, 35-54) of all benign biopsies.

“These are indeed promising results,” Grönberg said in the release. “If we can introduce a more accurate way of testing for prostate cancer, we’ll spare patients the unnecessary suffering and save resources for society.”

The researchers acknowledged several limitations. The performance of STHLM3 in a retesting situation could not be assessed because the study only called for it to be administered to each patient once. Additionally, because this was a diagnostic trial, long-term outcomes such as mortality could not be addressed. Also, at the time of study initiation, Gleason 7 was determined to be the primary outcome, although what score determines clinically significant prostate cancer remains debated.

STHLM3 will be available in Sweden as of March. Grönberg and his team plan to validate its use in other countries, as well as various ethnic groups. – by Anthony SanFilippo

Disclosure: Grönberg and another researcher have patents pending or are part of patent applications licensed to Thermo Fischer Scientific, a company that provided the protein and genetic marker assays for this study and a company with which Karolinska Institutet collaborates to develop the technology for the STHLM3. The other researchers report no relevant financial disclosures.