212 CHAPTER 6 Urological neoplasia
Prostate cancer grading
Adenocarcinoma of the prostate is graded using the Gleason system (see Fig. 6.4). Microscopically, adenocarcinoma is graded as a pattern 1 to 5 according to its gland-forming differentiation at relatively low magnification. Cytological features play no part in this grading system.
Since most are multifocal, an allowance is made by adding the two dominant grades to give a sum score between 2 and 10. If only one pattern is observed, the grade is simply doubled. The system is used with needle biopsies, TURP, and radical prostatectomy specimens.
Tertiary Gleason score is sometimes reported on radical prostatectomy specimens and represents the third-most prevalent grade present on the entire surgical specimen and may have prognostic significance if high grade.
Gleason scores 2–4 are considered well differentiated; 5–7 are moderately differentiated; and 8–10 are poorly differentiated. In practice, over 80% of PCs are graded 6 or 7, and, fortunately, only 15% are graded 8–10. Gleason score of less than 6 are uncommon in modern series.
Among expert pathologists, there is good interobserver reproducibility with Gleason scoring. However, scores assigned to needle biopsies are lower than those assigned to the subsequent radical prostatectomy specimen in 30% of cases, while overgrading on needle biopsy is less commonly seen.
The importance of the Gleason score is that it correlates well with prognosis, stage for stage, however the patient is managed. For example, a Gleason 4+4 = 8 adenocarcinoma carries a worse prognosis than a 3+3 = 6 cancer of equivalent stage. Moreover, cancers of the same Gleason score have a worse prognosis if the predominant grade is higher (for example, 4+3 = 7 is worse than 3+4 = 7).
Some men with low-grade tumors develop high-grade tumors after several years. This is most likely due to clonal expansion of high-grade cells rather than to dedifferentiation of low-grade tumor cells. In general, largevolume tumors are more likely to be high-grade than low-volume tumors, but occasionally exceptions are seen.
Finally, caution must be taken when Gleason-scoring prostate tissue that has been subjected to certain interventions, such a hormonal or radiation therapy. It is well recognized that prostate cancer treated with androgen ablation exhibits changes very similar to those seen in Gleason scores 8–10.
It is possible that even treatment of BPH with 5A-reductase inhibitors could adversely affect the Gleason score of cancer present in the gland. Pathologists should be informed of these important aspects of the patient history to provide the most accurate Gleason scores.
PROSTATE CANCER GRADING 213
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Figure 6.4 A diagrammatic representation of the Gleason grading system for prostate cancer. The grade depends on the structure of the prostatic glands and their relationship to the stromal smooth muscle.
214 CHAPTER 6 Urological neoplasia
Risk stratification in management of prostate cancer
Prostate cancer treatment options have varying levels of success. A challenge is to choose the most appropriate therapy based on the risk of disease progression with a given treatment and based on an individual’s cancer characteristics. It is often useful to assign a relative risk to an individual.
The risk groups were established from literature and are based on known prognostic factors: PSA biopsy Gleason score, and AJCC TNM stage. One typical system described by D’Amico1 is described below.
This is risk of PSA progression post-therapy and not overall or disease specific-survival.
•Low risk: stages T1c and T2a, PSA level of 10 ng/mL or less, and biopsy Gleason score of 6 or less (<25% PSA progression at 5 years posttherapy)
•Intermediate risk: PSA levels 10–20 ng/mL or lower, biopsy Gleason score of 7, or clinical stage T2b (25–50% PSA progression at 5 years post-therapy)
•High risk: T2c disease or a PSA level >20 ng/mL or a biopsy Gleason score of 8 or more (>50% PSA progression at 5 years post-therapy)
1 D’Amico, et al. (1998). Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 280 (11): 969–974.
MANAGEMENT OF LOCALIZED PROSTATE CANCER 215
General principles of management of localized prostate cancer
When considering treatment options for the man with localized prostate cancer, the following factors should be considered in the discussion:
•Patient’s life expectancy and overall health status
•Tumor characteristics, including Gleason score, tumor stage, PSA levels, PSA velocity and PSA doubling times
•Risk stratification
•Outcome tools such as nomograms1 and Partin tables (p. 208) that give specific likelihood of final pathological stage or specific
outcomes based on tumor characteristics and individual treatments (e.g., brachytherapy, radical prostatectomy, etc.)
1 http://www.mskcc.org/mskcc/html/10088.cfm