The role of volume‐weighted mean nuclear volume in predicting tumour biology and clinical behaviour in patients with prostate cancer undergoing watchful waiting

OBJECTIVE: To investigate whether the volume-weighted mean nuclear volume (MNV, the only means by which unbiased estimates of three-dimensional variables can be obtained from a two-dimensional section by stereological methods) at diagnosis correlates with tumour biology and clinical behaviour in patients with prostate cancer treated by watchful waiting. PATIENTS AND METHODS: In a prognostic study, 64 patients with clinically localized prostate cancer were followed prospectively with initial expectant management. The median (mean, range) follow-up was 22 (27, 6.0-68) months. The prostate specific antigen (PSA) doubling time (PSADT) was calculated by linear regression. The MNV was estimated using biopsy specimens, based on a stereological method, and compared with PSADT and traditional clinicopathological variables. RESULTS: PSADT was significantly associated with MNV, but not with other clinicopathological variables. The PSA 'rapid-riser' subset (PSADT<median value) had significantly larger MNVs than did the PSA 'slow-riser' (PSADT>or=median value) and PSA-stable subsets (P = 0.0017 and 0.004, respectively). On multivariate analysis using a stepwise Cox proportional hazards regression, only MNV remained independently significant as a predictor of clinical progression among the clinicopathological variables (P < 0.001). CONCLUSIONS: These findings suggest that cancer cell nuclear volume is significantly associated with tumour biology and behaviour in patients with prostate cancer. Although further study with a larger patient population is needed to confirm the findings, estimates of MNV may be an important prognostic indicator in men treated with watchful waiting.