Lack of association of prostate carcinoma nuclear grading with prostate specific antigen recurrence after radical prostatectomy

Purpose: Grading prostate cancer using the Gleason system relies only on ar chitectural tumor growth, in contrast to other systems, such as the WHO sys tem, which grade prostate carcinoma based on nuclear features as well as ar chitectural patterns. The prognostic significance of nuclear grading remain s controversial since most studies were performed before prostate specific antigen (PSA) screening became widely available. We evaluated the significa nce of nuclear grade for predicting PSA recurrence in a contemporary cohort of patients treated with radical prostatectomy for clinically localized pr ostate carcinoma. Materials and Methods: Nuclear grades 1 to 3 were determined in 141 consecu tive radical prostatectomies in 1995. Predominant and worst nuclear grade w as determined by a consensus of 3 pathologists. Statistical analysis compar ed nuclear grade with Gleason score using the chi-square test. The Cox prop ortional hazards analysis was performed to calculate the ability of nuclear grade, Gleason score and other variables to predict PSA recurrence. Results: We identified a significant association of Gleason score with wors t nuclear grade (p = 0.007). All 6 cases with a Gleason score of 8 or great er had a worst nuclear grade of 3, in contrast to 36 of 60 (60%) with a sco re 6 or less, in which the worst nuclear grade was 3. Of the 141 patients 3 1 (21.9%) had PSA recurrence at a median followup of 3.7 years. The univari ate Cox model revealed significant associations of PSA recurrence with Glea son score 8 or greater (hazards ratio 5.5, p = 0.005), extraprostatic exten sion (hazards ratio 3.4, p = 0.001), positive surgical margin (hazards rati o 2.6, p = 0.009), seminal vesicle involvement (hazards ratio 7.3, p <0.001 ), preoperative serum PSA (hazards ratio 1.03, p = 0.007), tumor stage (haz ards ratio 3.6, p = 0.001) and maximal tumor dimension (:hazards ratio 2.4, p <0.001). However, overall and worst nuclear grade did not predict PSA re currence (p = 0.89 and 0.13, respectively). Nuclear grade did not fit any m ultivariate model tested, which otherwise included Gleason score, log(PSA), surgical margin status, extraprostatic extension, seminal vesicle status, tumor size and pathological stage. By varying sample fixation time we also showed that benign prostate tissue in the same section as prostate carcinom a had grade 2 or 3 nuclear changes, that is moderate to marked anaplasia. Conclusions: High nuclear grade is associated with high Gleason score. Howe ver, prostate carcinoma with a Gleason score of 6 or less shows extreme var iability. Nuclear grade determined by light microscopy failed to predict PS A recurrence in a contemporary series of men with clinically localized pros tate cancer treated with radical prostatectomy. Nuclear morphology is subje ct to tissue fixation and processing artifact. Any nuclear morphometric stu dy must consider this artifact.