When Is Prostate Cancer Really Cancer?

DM Berman, JI Epstein

Prostate cancerRecent studies have established that pure Gleason score 3+3=6 cancers are unable to metastasize or kill. A less alarming proposed term for Gleason score 3+3=6 cancer to help prevent over-treatment of indolent prostate cancers is IDLE (indolent lesions of epithelial origin) tumor. Our article provides the molecular, histopathological, and clinical rationale as to why “cancer” should be retained for Gleason 3+3=6 tumor.
From an urologist’s standpoint, there are significant problems using the term IDLE tumor on biopsy. In 20% of cases with Gleason 3+3=6 on biopsy, there is unsampled Gleason pattern 4. For example, the designation IDLE tumor for a case with eight cores positive for Gleason 6 cancer in a 50-year-old man with PSA >10 ng/mL and palpable disease makes no sense, given the very high risk that there is more aggressive unsampled cancer that needs definitive therapy. IDLE tumors would potentially not be followed carefully, with the risk of missing unsampled higher-grade cancer or progression of cancer grade. 
One problematic aspect of the current Gleason grading system is that Gleason scores effectively range from 6 to 10. That men are told that their Gleason grade is 6 out of a possible 10 can lead to the misunderstanding that these tumors are more aggressive. To better reflect risk of harm from prostate cancer, we have proposed five prognostic grade grouping consisting of: Gleason <6; 3+4; 4+3; 8; 9–10. Patients need to be educated that most Gleason score 6 cancers can be followed with active surveillance. They can be told that they have a very good type of cancer that, in general, does not cause harm. However, there is a risk that there may be more aggressive cancer that was missed or that the cancer could change over time so that there is a need to follow them closely. 

Jonathan Epstein

ABSTRACT

KEY POINTS

  • Managing low-grade prostate cancers is a significant challenge, brought on by widespread adoption of prostate-specific antigen screening.
  • Physicians who diagnose this disease and discuss treatment options with patients may move toward correctly titrating management to fit low-risk patients by shifting the classification of low-risk prostate cancers into another diagnostic category, such as a benign tumor or a tumor of low malignant potential.
  • This shift is problematic in a biological sense, because low-grade prostate cancers clearly fulfill well-established definitions of cancer, and it would also be problematic in a practical sense, because risk classification by Gleason grading is often inaccurate and low-grade cancers may progress to high-grade cancers.
  • In the proposed system, indolent cancers currently scored as Gleason 6 out of 10 would be assigned a score of 1 out of 5.
  • The more accurate risk assessment provided by the new scoring system would be the start of a discussion between patients and physicians on how best to manage a cancer that is likely harmless

(Published with permission from Berman DM, Epstein JI Urol Clin N Am (2014) 41:339-346)
 

Several investigators have challenged the idea that low-grade cancers are a cause for concern, suggesting that the term cancer should not be applied to these tumors. This article reviews the defining features of cancer, and the diagnostic and prognostic classification systems currently used for prostate cancer. Logical, morphologic, and molecular evidence is presented to show that low-grade prostate cancers are correctly classified as cancer. The authors suggest, however, that 6 out of 10 on an aggressiveness scale is inappropriate for indolent cancer, and that a proposed reinterpretation of Gleason grading categories is a more logical way to address overtreatment.

DM Berman, JI Epstein
When Is Prostate Cancer Really Cancer?
Urol. Clin. North Am 2014 May 01;41(2)339-346