Cancer Volume of Lymph Node Metastasis Predicts Progression in Prostate Cancer

Abstract

Clinical outcome is variable in prostate cancer patients with regional lymph node metastasis. We studied 269 patients who had regional lymph node metastasis at the time of radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between January 1987 and December 1992. Two hundred fifty-three (94%) patients received androgen deprivation therapy within 90 days of radical prostatectomy. Patients ranged in age from 47 to 79 years (median, 67 years). Median follow-up was 6.1 years (range, 0.3-10.5 years). Nodal cancer volume (size) was measured by the grid-counting method. Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on systemic progression-free survival. Systemic progression was defined as the presence of distant metastasis documented by biopsies or radiographic examinations (abdominal computerized tomography, plain radiographs, or bone scan). Five-year progression-free survival was 90%. In predicting systemic progression using Cox multivariate analysis, only nodal cancer volume added significantly to the model containing the primary cancer variables (Gleason score, cancer volume, and DNA ploidy). The relative hazard rate for a doubling in nodal cancer volume was 1.6 (95% confidence interval, 1.3 to 2.0; p < 0.0001). Spearman rank analysis showed a correlation between nodal cancer volume and Gleason score of the primary cancer, the number of positive nodes, the aggregate length of metastases, and the largest nodal cancer diameter (correlation efficient = 0.37, 0.63, 0.96, and 0.95, respectively). Our data indicate that nodal cancer volume was the most significant nodal determinant of progression to distant metastasis in lymph node-positive prostate cancer patients. We recommend that the diameter of the largest metastasis be evaluated in patients with metastases, because this is a more powerful predictor of patient outcome than current methods, which recommend mere counting of the number of positive nodes.

Extranodal Extension in Lymph Node–Positive Prostate Cancer

“…Follow-up examinations after surgery included physical examination, serum prostate-specific antigen (PSA) measurements, chest radiography, and computerized tomography of the abdomen and pelvis, as clinically indicated (8,9). Radionuclide bone scanning was performed at least annually or as clinically indicated.…”

“…The radical prostatectomy and bilateral pelvic lymphadenectomy specimens were examined by frozen section at operation and subsequently by permanent sections, as previously described (8). Briefly, the apex and base of the prostate were amputated or submitted as en face (shave) margins, and the prostate was serially sectioned perpendicular to the long axis of the gland from the apex to the tip of the seminal vesicles.…”

“…The number of cancer sections submitted for frozen examinations from the radical prostatectomy specimens varied from 8 to 20 in this series, depending on cancer volume, prostate volume, and the preference of the pathologist. Approximately 14 prostate blocks were examined per case, and the method of sampling remained constant during the study period (8). All histologic evaluations were performed without knowledge of the clinical outcome.…”

“…ENE is a frequent histologic finding in lymph nodes with prostate cancer, but its prognostic significance has not been established. We previously demonstrated that nodal cancer volume is the single most important predictor of systemic progression-free survival in patients who are node positive and treated by radical retropubic prostatectomy, bilateral pelvic lymphadenectomy, and androgen deprivation (8). In this study, we evaluated the impact of ENE on survival and its association with other clinical and pathologic characteristics in a large number of patients who were node positive.…”

“…Although treatment may not cure such patients, regional lymph node metastasis may be the only manifestation of cancer progression in some patients (8,9). Identification of those who are at greatest risk for developing distant metastasis and mortality from prostate cancer will help stratify patients into prognostically distinct groups.…”