Association between very small tumor size and increased cancer-specific mortality following radical prostatectomy in node-positive prostate cancer

OBJECTIVE - To determine whether very small prostate cancers present in patients who also have lymph node (LN) metastases represent a particularly aggressive disease variant compared to larger node-positive tumors.

SUBJECTS/PATIENTS AND METHODS - We identified 37,501 patients diagnosed with prostate cancer between 1988 and 2001 treated with radical prostatectomy within the Surveillance, Epidemiology, and End Results database. The primary study variables were tumor size by largest dimension (stratified into: (1) microscopic focus only or 1 mm; (2) 2-15 mm; (3) 16-30 mm; (4) greater than 30 mm), regional LN involvement, and the corresponding interaction term. We evaluated the risk of 10-year prostate cancer-specific mortality (PCSM) using the Fine-Gray model for competing risks after controlling for race, tumor grade, T stage, receipt of radiation, number of dissected LNs, number of positive LNs, year of diagnosis, and age at diagnosis.

RESULTS - Median follow-up was 11.8 years. There was a significant interaction between tumor size and LN involvement (P-interaction < 0.001). In the absence of LN involvement (N=36,561), the risk of 10-year PCSM increased monotonically with increasing tumor size. Among patients with LN involvement (N=940), those with the smallest tumors had increased 10-year PCSM compared to patients with tumors sized 2-15 mm (24.7% vs. 11.8%; adjusted hazard ratio [AHR] = 2.84; 95% confidence interval [CI], 1.21 to 6.71; P = 0.017) or 16-30 mm (24.7% vs. 15.5%; AHR = 3.12; 95% CI, 1.51 to 6.49; P = 0.002) and similar 10-year PCSM compared to those with tumors greater than 30 mm (24.7% vs. 24.9%; P = 0.156).

CONCLUSIONS - In prostate cancer patients with LN involvement, very small tumor size may predict for higher PCSM compared with some larger tumors, even after controlling for other prognostic variables. These tumors might be particularly aggressive, beyond what is captured by pathological assessment of tumor grade and stage. This article is protected by copyright. All rights reserved.

BJU Int. 2015 Aug 1. doi: 10.1111/bju.13248. [Epub ahead of print]

Muralidhar V1, Mahal BA2, Nezolosky MD3, Beard CJ3, Feng FY4, Martin NE3, Efstathiou JA5, Choueiri TK6, Pomerantz MM6, Sweeney CJ6, Trinh QD7, Vander Heiden MG8, Nguyen PL3.

1 Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, 02115.
2 Harvard Medical School, Boston, MA, 02115.
3 Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, 02115.
4 Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109.
5 Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 02114.
6 Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
7 Department of Urology, Brigham and Women's Hospital, Boston, MA, 02115.
8 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139.