Pathologic evaluation of radical cystectomy specimens

Radical cystectomy and bilateral pelvic lymphadenectomy is the standard surgical treatment of muscle-invasive bladder carcinoma. Pathologic stage of the primary tumor and regional lymph nodes is the most important predictor of outcome.1, 2 The most recent 1997 Tumor-Node-Metastasis (TNM) staging system classifies the primary invasive tumor as confined to the bladder (Stage T2) or extravesical disease (Stage T3). The T3 category is subdivided into T3a (microscopic involvement of perivesical fat) and T3b (macroscopic extravesical mass) because T3b represents more advanced local disease and confers a worse prognosis than T3a tumor.1 Nodal status is classified simply as the presence or absence of nodal metastases. Positive nodes are subdivided into three general N catagories on the basis of nodal size (< 2 to > 5 cm) and number (single or multiple) of positive nodes.3 Tumors confined to the bladder and negative nodes have a favorable outcome, whereas tumors that have grossly spread beyond the bladder with positive nodes usually recur after radical cystectomy.1, 2 The total number of nodes retrieved in the specimen,4 the number of positive nodes,1, 4 and the margins of tumor involving fat5 may also have a substantial impact on prognosis. Adjuvant chemotherapy of bladder carcinoma is advised for patients with positive lymph nodes or gross tumor extension through the bladder wall. Thus, determining which patients have positive nodes (and identifying patients who are truly node negative) and the margins of local tumor extension could have a major impact on the management of individual patients and could markedly influence the outcome of clinical trials designed to assess the value of adjuvant therapy. Careful dissection of the fat surrounding the bladder and of the lymphatic tissue submitted either en bloc or separate from the bladder, searching the specimen for tumor and nodes. Individually submitted nodal packets are preferred because they are easier for the pathologist to dissect and they yield a greater number of nodes than en bloc specimens.8 Visual enhancement techniques, such as fat clearing, are probably not necessary, practical, or cost effective. Further, isolated microscopic nodal metastases identified using specialized techniques are of doubtful significance relative to the outcome of many cancers (i.e., breast, stomach, colon). Measurement of the margin of fat overlying palpable or gross tumor to determine margin status and distance of tumor from the margin. Submission of all lymph nodes, whether grossly negative, positive, or suspicious, in their entirety for microscopic examination. Examine both halves of each node if the first half is negative for tumor. Reporting of the total number of nodes examined and the total number of nodes involved with metastatic disease as well as the size of each positive node. (Some pathologists also note whether the tumor is confined to the subcapsular sinus, replaces the node entirely, or exhibits capsule perforation, since these pathologic nodal findings may discriminate different outcomes).9 Examination of at least 9, and preferably 14 or more, nodes to determine that a patient is truly node-negative.4, 10 Report if no nodes are found. Definition of primary tumor size, location, number, configuration (nodular or papillary), histologic type, grade, vascular invasion, and whether the tumor is confined or not confined to the bladder. Evaluation of the prostate gland for urothelial carcinoma. Assign a P category for tumor involvement of the prostate separate from that in the bladder, stratified by in situ (urethra, ducts, or glands) versus stroma invasion, and determine the margin status of invasive tumor relative to the prostate capsule.11 Evidence suggests that the pathologic stage of the primary bladder tumor correlates best with prognosis rather than the stage of tumor within the prostate. Accurate assessment of the extent of the tumor in cystectomy specimens is a combination of the aggressiveness of the surgeon in resecting widely around the bladder and in removing lymph nodes and the diligence of the pathologist in searching the specimen for tumor in fat and lymph nodes. Neither radical cystectomy nor pathologic evaluation of cystectomy specimens is standardized, and the quality of both varies widely. More uniformity of both surgical technique and pathologic assessment is needed. Improving the quality of medical care in both of these areas could have a major impact on overall outcome and may even prove to be as important as likely improvements in adjuvant chemotherapy.