Jean B. de Kernion

International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy

PURPOSE We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Clinical management of foreign bodies of the genitourinary tract.

Purpose: The variety of foreign bodies inserted into or externally attached to the genitourinary tract defies imagination and includes all types of objects. The frequency of such cases renders these objects an important addition to the diseases of the urinary organs.Materials and Methods: We performed a computerized MEDLINE search followed by a manual bibliographic review of cross-references. These reports were analyzed and the important findings summarized.Results: Our review encompassed approximately 800 single case reports on foreign bodies in the English world literature published between 1755 and 1999. We structured the range of introduced objects, by referring to origin and material as well as the genitourinary organs involved. Furthermore, we noted symptomatology and diagnoses, including psychological involvement, as well as possible treatment options.Conclusions: The most common motive associated with foreign bodies of the genitourinary tract is sexual or erotic in nature. The most suitable method...

Is adrenalectomy a necessary component of radical nephrectomy? UCLA experience with 511 radical nephrectomies.

PURPOSE We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. MATERIALS AND METHODS The records of 511 patients undergoing radical nephrectomy with ipsilateral adrenalectomy for renal cell carcinoma at our medical center between 1986 and 1998 were reviewed. Mean patient age was 63.2 years (range 38 to 85), and 78% of the subjects were males and 22% were females. Patients were divided into subgroups of 164 with localized (stage T1-2 tumor, group 1) and 347 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. Staging of tumors was performed according to the 1997 TNM guidelines. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological findings to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. RESULTS Of the 511 patients 29 (5.7%) had adrenal involvement. Average size of the adrenal tumor was 3.86 cm. (standard deviation 1.89). Tumor stage correlated with probability of adrenal spread, with T4, T3 and T1-2 tumors accounting for 40%, 7.8% and 0.6% of cases, respectively. Upper pole intrarenal renal cell carcinoma most likely to spread was local extension to the adrenal glands, representing 58.6% of adrenal involvement. In contrast, multifocal, lower pole and mid region renal cell carcinoma tumors metastasized hematogenously, representing 32%, 7% and 4% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 8.9 cm., range 3 to 17) and adrenal involvement (independent of stage) was not statistically significant. Renal vein thrombus involvement was demonstrated in 8 of 12 cases (67%) with left and 2 of 9 (22%) with right adrenal involvement. Preoperative CT demonstrated 99.6% specificity, 99.4% negative predictive value, 89.6% sensitivity and 92.8% positive predictive value for adrenal involvement by renal cell carcinoma. CONCLUSIONS With a low incidence of 0.6%, adrenal involvement is not likely in patients with localized, early stage renal cell carcinoma and adrenalectomy is unnecessary, particularly when CT is negative. In contrast, the 8.1% incidence of adrenal involvement with advanced renal cell carcinoma supports the need for adrenalectomy. Careful review of preoperative imaging is required to determine the need for adrenalectomy in patients at increased risk with high stage lesions, renal vein thrombus and upper pole or multifocal intrarenal tumors. With a negative predictive value of 99.4%, negative CT should decrease the need for adrenalectomy. In contrast, positive findings are less reliable given the relatively lower positive predictive value of this imaging modality. Although such positive findings may raise suspicion of adrenal involvement, they may not necessarily indicate adrenalectomy given the low incidence, unless renal cell carcinoma with risk factors, such as high stage, upper pole location, multifocality and renal vein thrombus, is present.

Renal Cell Carcinoma With Tumor Thrombus: Is Cytoreductive Nephrectomy For Advanced Disease Associated With An Increased Complication Rate?

PURPOSE We examined whether cytoreductive nephrectomy in patients with venous tumor thrombus and metastatic disease is associated with more complications than in those with thrombus without metastatic disease. MATERIALS AND METHODS Between 1989 and 2000, 74 patients with renal vein extension, 87 with inferior vena caval extension and 491 without tumor thrombus underwent nephrectomy at our institution. Metastatic and nonmetastatic renal vein extension in 51 and 23 cases, inferior vena caval extension in 54 and 33, and nontumor thrombus in 171 and 320, respectively, were compared for symptoms at presentation, surgical data, mortality and complications. RESULTS For nonmetastatic and metastatic inferior vena caval extension presenting symptoms, hospital stay, surgical time and the number of patients undergoing thoraco-abdominal incision, lymph node dissection, venacavotomy alone for thrombus and adrenal sparing surgery were similar. Five patients with thrombus died intraoperatively or postoperatively, including 3.1% with and 0.8% without thrombus (p = 0.03), while 3 had metastatic (2.3%) and 2 (2.6%) had nonmetastatic disease. The rate of postoperative complications was higher in thrombus cases overall but there was no difference in nonmetastatic and metastatic disease with thrombus. On multivariate analysis inferior vena caval thrombus (odds ratio 10.5), adjacent organ resection due to locally advanced tumor (odds ratio 6), partial nephrectomy (odds ratio 3.8), regional lymph node involvement (odds ratio 1.7) and lower preoperative hemoglobin (odds ratio 1.6) were independent variables predicting bleeding requiring transfusion. Inferior vena caval thrombus (odds ratio 1.7) and adjacent organ resection (odds ratio 2) were also associated with nonhemorrhagic complications. Systemic metastasis was not an independent risk factor in either analysis. CONCLUSIONS To our knowledge there are no published data comparing surgical complications in patients with metastatic and nonmetastatic renal cell carcinoma who have gross tumor thrombus. Cytoreductive surgery in patients with thrombus and metastasis is not associated with an increase in the extent of surgery, morbidity or mortality compared with their counterparts with nonmetastatic disease.

Antibody-Based Profiling of the Phosphoinositide 3-Kinase Pathway in Clinical Prostate Cancer

Purpose: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. Experimental Design: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Results and Conclusions: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.

Blood loss and the need for transfusion in patients who undergo partial or radical nephrectomy for renal cell carcinoma.

PURPOSE We assessed blood loss and subsequent transfusion associated with nephrectomy performed for suspected renal cell carcinoma to establish guidelines for preoperative autologous blood donation and identify a subgroup of patients that may benefit from erythropoietin administration. MATERIALS AND METHODS We retrospectively reviewed the charts of 211 patients who underwent partial (73%) or radical (23%) nephrectomy for presumed renal cell carcinoma at our institution between 1990 and 1999. Patients were divided into groups 1-44.5% treated with radical nephrectomy for localized disease, 2-21.3% radical nephrectomy for metastatic lesions invading the renal vasculature or inferior vena cava, 3-8% radical nephrectomy for metastatic disease with locally extensive lesions and 4-26.5% partial nephrectomy for localized lesions. Patient charts were evaluated for preoperative and postoperative hematocrit, estimated blood loss, transfusions received, surgical complications and underlying disease. RESULTS Median estimated blood loss was 200, 400, 250 and 555 cc in groups 1 to 4, respectively. However, patients in groups 2 and 3 had a substantially greater range of blood loss than those in groups 1 and 4, respectively. The incidence of those with a blood loss of greater than 1 l. was 7%, 36%, 24% and 11% in groups 1, to 4, respectively. The incidence of those requiring transfusion was significantly lower in group 1 than in groups 2 to 4 (18% versus 44%, 24% and 30%, respectively, p <0.009). Mean transfusion requirement plus or minus standard deviation was significantly greater in groups 2 and 3 than in 1 and 4 (2.3 +/- 1.08, 5.5 +/- 4.4, 11.3 +/- 9.6 and 2.3 +/- 1.7 units, respectively, p <0.05). No significant difference was noted in the change in hematocrit as a result of surgery in the 4 groups (p >0.05). Similarly underlying disease and operative complications did not have a significant effect on blood loss or transfusion (p >0. 05). CONCLUSIONS Radical or partial nephrectomy for localized renal cell carcinoma leads to consistent and well tolerated operative blood loss that rarely results in the need for substantial transfusion. In contrast, nephrectomy for advanced disease may cause a risk of greater blood loss and subsequent need for the transfusion of multiple units of blood. While preoperative autologous blood donation may have limited value in this regard due to the high cost and number of units needed, preoperative erythropoietin administration may be a viable option. Prospective randomized studies are currently planned.