Risk stratification for positive lymph nodes in prostate cancer
ABSTRACT To evaluate the risk of positive lymph nodes using preoperative clinical parameters.
We reviewed our prospectively collected database for all patients who received RRP and PLND between January 1993 and November 2005 as primary therapy for prostate cancer. We excluded patients who had hormonal ablation or radiation therapy prior to surgery and patients with missing PSA, clinical stage, or biopsy Gleason score. We evaluated risk for nodal disease using the following definitions: low risk: PSA <or=10 ng/mL, clinical stage <or=T(2a), and Gleason score <or=6; intermediate risk: PSA 10 to 20 ng/mL, clinical stage >or=T(2b), or Gleason score of 7; and high risk: PSA >or=20 ng/mL, or clinical stage >or=T(2c), or Gleason score >or=8. Logistic regression was used to determine the association between the risk groups and pathologic lymph node involvement, and a receiver operating characteristics (ROC) curve was constructed to evaluate the performance of the stratification scheme in detecting nodal disease.
A total of 760 patients with 43 (5.7%) patients with node-positive disease were available for analysis. Risk classification was significantly associated with positive nodes (P<0.001), even after controlling for year of surgery and age. The area under the ROC curve was 0.77 (95% CI: 0.69, 0.83). Omitting PLND in the low-risk group would have spared 368 (49.2%) of the entire cohort with a false-negative rate of 5/369 (1.3%) for the low-risk group, and 5/760 (0.7%) for the entire cohort. Sensitivity was 88.4%, and negative predictive value was 98.7%.
Patients can be risk stratified for node-positive disease and potentially excluded from lymphadenectomy with minimal risk.
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ABSTRACT: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases.PLoS ONE 08/2010; 5(8):e12262. DOI:10.1371/journal.pone.0012262 · 3.53 Impact Factor
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ABSTRACT: • To determine the incidence and significance of lymph nodes in the anterior prostatovesicular lymphofatty tissue. • One hundred and twenty patients with clinically localized prostate cancer underwent robot-assisted laparoscopic radical prostatectomy with excision of anterior prostatovesicular tissue at a single institution over a 6-month period. • Tissue was sent for pathological analysis. • Separate pelvic lymph node dissection was carried out in moderate-risk and high-risk patients. • A total of 20 out of 120 patients (16.7%) had lymph nodes in the anterior lymphofatty tissue. • Average lymph node number when present was 1.5 (one to three). • Pathological assessment of the lymph nodes revealed metastatic prostate cancer in 3 out of 120 (2.5%) patients, each of whom had adverse pathological features. • Patients with metastatic lymph nodes in the anterior tissue did not have cancer involvement of the pelvic lymph nodes. • Patients with lymph nodes found in the anterior lymphofatty tissue were slightly younger but were otherwise similar with respect to other demographics, prostate-specific antigen, biopsy Gleason score, clinical stage, pathological stage, pathological Gleason score, seminal vesicle invasion, and margin status. • Anterior lymphofatty tissue overlying the prostate occasionally contains lymph nodes that can harbour malignant disease and routine excision may eradicate regional tumour burden. • Of patients with nodes, 15% were found to have malignant involvement. • The long-term impact on progression-free and overall survival requires further study.BJU International 08/2011; 109(4):603-7. DOI:10.1111/j.1464-410X.2011.10336.x · 3.13 Impact Factor