“The new system should make treatment options clearer to physicians and patients,” says Jonathan I. Epstein, M.D., a professor of pathology, oncology and urology at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center. While the Gleason system has 25 potential scores, the novel method he and his team developed has just five grades, with “1” indicating the least aggressive cancer and “5” meaning the cancer with the worst prognosis. A report on the work appears in an upcoming issue of the journal European Urology.
The novel five-tiered grading system has already been accepted by the World Health Organization and the International Society of Urological Pathology. The Johns Hopkins investigators plan to promote its use worldwide and in parallel with the Gleason Scale for at least a while to both further test it and ease the transition to what they say is a far simpler grading method.
Epstein and his team first proposed the five-grade system, which was based on an analysis of data from more than 7,000 prostate cancer patients at The Johns Hopkins Hospital, in 2013. To verify the accuracy of the new stratification, researchers analyzed data obtained from tissues of more than 20,000 men whose prostates had been surgically removed between 2005 and 2014 at five medical institutions, including The Johns Hopkins Hospital. They also included data from biopsies of more than 5,000 men treated with radiotherapy at two medical centers during the same period of time.
Gleason grading is composed of a combination of scores that reflects the potentially aggressive characteristics of cancer tissues in the prostate, such as the shape and patterns of tumor cell growth. In the new study, researchers analyzed and compared cancer recurrence rates for the commonly used combinations of Gleason scores and the new five-grade system for both surgery and radiotherapy patients.
The results suggested that the prognostic discrimination for the new grading system was higher than the most commonly used combinations of the Gleason scores. For example, the original Gleason system typically considers Gleason score 7 as requiring radiation therapy. However, the new system broke up Gleason 7 into Grade Group 2 and Grade Group 3, in which 3’s prognosis is twice as bad as 2’s. The difference in Grade Groups is especially critical for selecting a therapy — Grade Group 3 is treated with hormonal therapy in addition to radiation, which carries significant side effects, whereas Grade Group 2 is treated only with radiation. Similarly, the Gleason scores 8–10 are typically considered one grade, yet in the new grading system, these grades can be split into Grade Group 4 and Grade Group 5, where again the latter is twice as aggressive. Forty percent of the men in the study fell into either Grade Group 2 or 3 and would be affected by distinguishing between the two, and 10 percent of the men fell into either Grade Groups 4 or 5. Thus, using the new system, 50 percent of the men in the study potentially received a more appropriate treatment than they would have had their doctors used the most common combinations of the Gleason score.
Epstein says the Gleason grading is confusing for physicians who have to deal with several potential scores that stem from the analysis of the most dominant tissue patterns of the prostate tumor. The sum of scores provides a final result that ranges on a scale of 2 to 10, which is confusing for patients and contributes to their fear. When patients are told they have cancer scored 6 in the Gleason scale, for example, they tend to assume their cancer is more aggressive than it may be and that it undoubtedly needs treatment, Epstein says. Patients’ emotions often fuel overtreatment of low-risk prostate tumors that are less likely to spread or kill them.
“The prostate cancer that we see today is not the same that we used to see four decades ago,” Epstein says, “because diagnoses and treatments have evolved and prognoses have improved.” In the new system, the Gleason score 6 corresponds to the Grade Group 1, in which these are typically tumors that haven’t grown beyond the prostate. In this case, treatments, such as radical prostatectomy or radiotherapy, are not necessary for most men because prostate cancer grows slowly.
“An older man with Grade Group 1 cancer will mainly need active surveillance of the tumor and probably won’t require radiotherapy or surgery, which sometimes have significant side effects, such as impotence or incontinence,” Epstein says. Meanwhile, a younger man will need close follow-ups to evaluate pertinent treatments, Epstein explains, because he may be prone to develop more aggressive cancer during his life.
Except for nonmelanoma skin cancer, prostate cancer is the most common cancer among men in the United States, researchers say, and accurately grading the disease is crucial for providing the appropriate treatment. Prostate cancer is also common in northern European men and is becoming more prevalent among Asian men. “This new system will benefit patients globally,” Epstein adds.
In 2014, more than 230,000 men were diagnosed with prostate cancer and nearly 30,000 died from the disease, according to data from the American Cancer Society.
Other researchers involved in the study include Misop Han of Johns Hopkins; Michael J. Zelefsky, Daniel D. Sjoberg, Andrew J. Vickers, Victor E. Reuter, Samson W. Fine and James A. Eastham of the Memorial Sloan Kettering Cancer Center; Joel B. Nelson and Anil V. Parwani of University of Pittsburgh Medical Center; Lars Egevad, Peter Wiklund and Tommy Nyberg of Karolinska Intstitute; and Cristina Magi-Galluzzi, Chandana A. Reddy, Jay P. Ciezki and Eric A. Klein of Cleveland Clinic.
No external funding was received for the analysis.
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