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Re: Do Adenocarcinomas of the Prostate with Gleason Score (GS) ≤6 Have the Potential to Metastasize to Lymph Nodes?

By: Kyle Richards and Scott Eggenerlowast

European Urology, Volume 63 Issue 5, May 2013

Published online: 01 May 2013

Abstract Full Text Full Text PDF (69 KB)

Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JIAm J Surg Pathol 2012;36:1346–52Experts’ summary:The investigators hypothesize that when using the 2005 International Society of Urologic Pathology classification system, Gleason ≤6 prostate cancer (PCa) cannot metastasize to pelvic lymph nodes. Four large radical prostatectomy databases identified >14 000 cases of Gleason ≤6, with 22 (0.15%) having LN metastasis, of which 19 were available for review. On contemporary re-review, all 19 contained Gleason 4 elements. Therefore, the authors conclude contemporary Gleason 6 cannot metastasize to lymph nodes.Experts’ comments:The implications of this manuscript are profound. Using a histologic definition, Gleason 6 is undeniably cancer. However, if truly not capable of metastasizing, what are the implications for patient care? More provocatively, because the clinical definition of cancer implies some quantifiable risk of lethal potential, should Gleason 6 be called cancer?

A recent review concluded Gleason 6 does not meet any of the six classic hallmarks of cancer [1]. In a series of 9557 patients with organ-confined Gleason ≤6 (without contemporary re-review) that underwent radical prostatectomy, only three died from PCa [2]. This finding was corroborated in the Physicians Health Study, in which no patient died of Gleason ≤6 following prostatectomy after >2600 person-years of follow-up [3]. Of course, surgery alters the natural history, and longer follow-up is mandatory; nevertheless, the available data suggest true Gleason 6 has an exceedingly low, perhaps infinitesimally small, risk of leading to death from PCa.

Does this pathologic and clinical data warrant rethinking our nomenclature? Modifications to the Gleason system are not unprecedented. Gleason patterns 1–2, described in 1966, are now considered normal variants. Perhaps a time will come when Gleason 6 is considered a risk factor for harboring higher-grade cancers that require diagnosis and treatment.

However, there are several potential pitfalls with regard to relabeling Gleason 6: understaging, missed opportunity for cure, and medical liability [4]. Currently, the diagnosis of localized PCa can lead to a wide range of treatment-related outcomes, from life-saving to life-altering. Management decisions would be easier if the prostate was on a man's elbow.

We believe the holy grail is the elusive pathologic, radiographic, or serologic tool to definitively determine the prostate does not contain higher-grade cancers. In that setting, it would be difficult to substantiate immediate treatment of Gleason 6 cancer. In contrast, definitive identification of higher-grade cancers would warrant treatment in a large proportion of men with a reasonable life expectancy.

Conflicts of interest

S. Eggener: Myriad Genetics: research support, consultant; Genomic Health: consultant. K. Richards has nothing to disclose.

References

  • [1] H.U. Ahmed, M. Arya, A. Freeman, et al. Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy?. Lancet Oncol. 2012;13:e509-e517 Crossref.
  • [2] S.E. Eggener, P.T. Scardino, P.C. Walsh, et al. Predicting 15-year prostate cancer specific mortality after radical prostatectomy. J Urol. 2011;185:869-875 Crossref.
  • [3] J.R. Stark, S. Perner, M.J. Stampfer, et al. Gleason score and lethal prostate cancer: does 3+4=4+3?. J Clin Oncol. 2009;27:3459-3464 Crossref.
  • [4] H.B. Carter, A.W. Partin, P.C. Walsh, et al. Gleason score 6 adenocarcinoma: should it be labeled as cancer?. J Clin Oncol. 2012;30:4294-4296 Crossref.

Footnotes

University of Chicago, Chicago, IL, USA

lowast Corresponding author.

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