Progression and long-term survival after simple enucleation for the elective treatment of renal cell carcinoma: experience in 107 patients

PURPOSE: We present our findings in a series of T1a renal cell carcinoma treated with elective simple enucleation, specifically reporting the incidence of local recurrence, and progression-free and disease specific survival rates. MATERIALS AND METHODS: A total of 107 patients who underwent elective nephron sparing surgery performed with simple enucleation from January 1989 to December 2000 were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free from distant metastases before surgery (M0). Patient status was last evaluated in July 2004. Mean (median, range) followup was 88.3 (84, 44 to 175) months. RESULTS: Pathological review according to the 2002 TNM classification showed that 95% (102 of 107) of tumors were pT1a, 4% (4 of 107) pT1b and 1% (1 of 107) pT3a. Mean (SD, median, range) tumor greatest dimension was 2.7 (0.93, 2.5, 0.6 to 5) cm. None of the patients died in the immediate postoperative period (within the first 30 days). There were no major complications such as bleeding and urinary leakage/urinoma requiring reoperation. The 5 and 10-year cancer specific survival was 99% and 97.8%, respectively. The 5 and 10-year progression-free survival was 98.1% and 94.7%, respectively. Overall 3 patients had disease progression (2.8%) of whom 2 (1.9%) were local recurrence, 1 alone and 1 associated with distant metastases diagnosed 12 months earlier. CONCLUSIONS: Simple tumor enucleation is a safe and acceptable approach for elective nephron sparing surgery. It provides excellent long-term progression-free and cancer specific survival rates, and is not associated with an increased risk of local recurrence compared with partial nephrectomy.     

A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials

PURPOSE: We developed a clinically useful scoring algorithm to predict cancer specific survival for patients with clear cell metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: We studied 727 patients treated with radical nephrectomy for clear cell RCC from 1970 to 2000 who had distant metastases at nephrectomy (285) or in whom metastases subsequently developed (442). A scoring algorithm to predict cancer specific survival was developed using the regression coefficients from a Cox proportional hazards model. RESULTS: There were 606 deaths from clear cell RCC at a median of 1.0 years (range 0 to 14) following metastatic RCC. Constitutional symptoms at nephrectomy (+2), metastases to the bone (+2) or liver (+4), metastases in multiple simultaneous sites (+2), metastases at nephrectomy (+1) or within 2 years of nephrectomy (+3), complete resection of all metastatic sites (-5), tumor thrombus level I to IV (+3), and the primary pathological features of nuclear grade 4 (+3) and histological tumor necrosis (+2) were significantly associated with death from RCC. All patients started with a score of 0 and points were added or subtracted as indicated in parentheses. Cancer specific survival rates at 1 year were 85.1%, 72.1%, 58.8%, 39.0%, and 25.1%, respectively, for patients with scores of -5 to -1, scores of 0 to 2, scores of 3 to 6, scores of 7 or 8, and scores of 9 or more. CONCLUSIONS: This scoring algorithm can be used to predict cancer specific survival for patients with metastatic clear cell RCC.     

SERUM CYFRA 21–1 IN PATIENTS WITH INVASIVE BLADDER CANCER AND ITS RELEVANCE AS A TUMOR MARKER DURING CHEMOTHERAPY

Purpose:

Previous studies have shown that serum levels of the degradation products of cytokeratins could be used as surrogate markers in the diagnosis and followup of patients with solid tumors, including tumors of the bladder.

Materials and Methods:

The soluble cytokeratin 19 fragment CYFRA 21-1 was measured by solid phase radioimmunoassay in the serum of 142 patients with invasive transitional cell cancer of the bladder. Of the patients 56 had clinical stage I to III locally confined disease (T1-4aN0M0) and 86 had stage IV metastatic disease with lymph node and/or distant metastases. A control group consisted of 33 healthy volunteers. In a subgroup of 49 patients with metastatic disease receiving combined platinum based chemotherapy serum CYFRA 21-1 was determined prior to the initiation of therapy and after the documentation of response.

Results:

Abnormal CYFRA 21-1 was observed in 7% of patients with locally invasive disease and in 66% of those with metastatic disease (p <0.0001). There was no correlation of CYFRA 21-1 with tumor differentiation. Patients with abnormal CYFRA 21-1 showed statistically significant worse median overall survival. Moreover, in the subgroup of patients with metastatic disease receiving chemotherapy CYFRA 21-1 levels correlated with the response to treatment.

Conclusions:

Patients with transitional cell cancer of the bladder with evidence of distant metastases showed a significant increase in serum CYFRA 21-1. During chemotherapy CYFRA 21-1 appears to be a potentially sensitive and useful indicator for monitoring treatment response.     

Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy

PURPOSE: Renal cell carcinoma (RCC) has traditionally been staged using a purely anatomical staging system. Although current staging systems provide good prognostic information, data published in the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors not currently included in traditional staging systems. This review highlights such controversies and provides an update on current staging modalities, prognostic factors and targeted molecular therapy for RCC. MATERIALS AND METHODS: A comprehensive review of the peer reviewed literature was performed on the topic of current staging modalities, validated prognostic factors, predictive nomograms, molecular markers and targeted molecular therapy for RCC. RESULTS: A staging system for malignant disease such as RCC uses various characteristics of tumors to stratify patients into clinically meaningful categories, which can be used to provide patients with counseling regarding prognosis, select treatment modalities and determine eligibility for clinical trials. The TNM staging system is currently the most extensively used one. However, it has undergone recent systematic revision due to rapidly emerging data from longer patient followup. The identification of various histological and symptomatic factors has led groups at many centers to develop more comprehensive staging systems that integrate these factors and include patients with metastatic and local disease. While integrated staging systems have improved RCC staging, the recent discovery of molecular tumor markers is expected to revolutionize RCC staging in the future and lead to the development of new therapies based on molecular targeting. CONCLUSIONS: Staging systems for RCC serve as a valuable prognostic tool. Several new patient and tumor characteristics have been reported to be important prognostic factors and they have been integrated into current staging systems. In addition, the field of RCC is rapidly undergoing a revolution led by molecular markers and targeted therapies. With this information urologists will be updated with the most current and comprehensive staging strategies, and be provided with a glimpse of the molecular and patient specific staging and treatment paradigms that will in our opinion transform the future management of this malignancy.     

Renal cell carcinoma with renal vein and inferior vena caval involvement: clinicopathological features, surgical techniques and outcomes

PURPOSE: We present a contemporary review of patients with renal cell carcinoma (RCC) in whom renal vein/inferior vena caval thrombus was treated with radical nephrectomy and thrombectomy. MATERIALS AND METHODS: A total of 220 patients underwent radical nephrectomy for RCC at our institution from 1998 to 2002. Of them 49 patients with renal vein/inferior vena caval involvement (T3b/c) were selected for review. We evaluated demographics, presenting symptoms, imaging modalities, clinical staging, pathological features, adjuvant treatment and clinical outcomes. We also evaluated surgical incisions, liver mobilization procedures, blood loss, transfusion requirements and perioperative mortality/morbidity. RESULTS: Gross hematuria was the most common presenting symptom, seen in 22 patients (45%), followed by constitutional symptoms in 8 (16%). Stage T3b/c was clinically diagnosed in 44 patients, while 2 had T2 and 2 had T4 disease. A subcostal incision was made in 30 patients, a chevron incision was made in 18, and a sternotomy and flank incision were made in 1. Liver mobilization was necessary in 13 patients and 2 required a Pringle maneuver. Cardiopulmonary bypass was performed in a single patient. Lymph node involvement was seen in 4 patients (8%) and distant metastases were present in 10 (20%). Median tumor size was 10 cm. Clear cell carcinoma was most common, as seen in 42 patients. Early (30-day) mortality in this series was 8%. At a median followup of 15 months 21 patients (43%) were without evidence of disease, 14 (29%) had disease, 8 (16%) had died of disease and 2 (4%) had died of other causes. None of the patients with lymph node involvement survived beyond 8 months after surgery. Tumor grade and T stage were found to be significant negative predictors of survival on univariate analysis. CONCLUSION: Most patients with RCC and tumor thrombus are symptomatic at presentation and metastatic disease at presentation is not uncommon. These results support the role of aggressive surgical treatment as the best initial management of these tumors. The majority of tumors can be approached and safely controlled without the need for a thoracoabdominal incision. While surgery provides modest disease-free survival, most patients should be offered immunotherapy, particularly those with advanced stage, grade, nodal involvement or metastases.     

Local recurrence after cystectomy and survival of patients with bladder cancer: a population based study in greater amsterdam

PURPOSE: We determined retrospectively in a population based study the survival of patients with bladder cancer and the local recurrence rate (LRR) after cystectomy. MATERIALS AND METHODS: All patients with bladder cancer diagnosed between 1988 and 2001 (vital status updated until September 2003) were selected from the Amsterdam Cancer Registry, which covers a population of 2.84 million individuals. For all patients who underwent cystectomy between 1988 and 1997 at 18 participating hospitals information on local recurrence and vital status was collected from the medical records. RESULTS: Five-year relative survival in all 8,321 bladder cancer cases combined was 75%. For clinical stage 0-a this was 99%, decreasing to 85% for stage 0-is and 82% for stage I, and to 44%, 28% and 9% for stages II to IV, respectively. Five-year relative survival after cystectomy was 81%, 44% and 23% for stages II to IV, respectively. The LRR after cystectomy was 19% in all 566 cases and all institutions combined. The LRR increased with higher pT stage and it achieved 11%, 23% and 31% for stages II to IV, respectively. It was slightly lower at oncological centers than at community hospitals (18% vs 20%, not significant). CONCLUSIONS: Survival is higher than the European average but below the value in the United States. Only 1 of 3 stages II-III cases was treated with cystectomy. Relatively high stage specific survival is experienced after cystectomy despite local recurrence in 1 of 5 patients.     

Clinical and pathological characteristics of unstageable prostate cancer: analysis of the CaPSURE database

PURPOSE: The new and older clinical staging systems for prostate cancer overlook a group of patients in whom abnormal digital rectal examinations (DREs) do not correlate with prostate biopsy findings. These cases are clinically unstageable. We evaluated the prevalence and pathological characteristics of these patients and stratified them into the 1997 American Joint Committee on Cancer clinical staging categories. MATERIALS AND METHODS: Using the CaPSURE database, a longitudinal disease registry of patients with various stages of prostate cancer, the unstageable cohort was identified. The postoperative pathological stage distribution of the unstageable cohort was used to assign the appropriate preoperative clinical stages in retrograde fashion. Pearson product moment correlation was used to establish the best clinical stage for this unstageable group. RESULTS: A total of 5,543 patients with recorded DREs were evaluated, of whom 2,610 (47%) had an isolated unilateral abnormality on DRE. A total of 235 patients (9%) had prostate needle biopsies positive only on the contralateral side, yielding an unstageable prevalence of 4.2%. Of the cohort 102 patients (44%) underwent radical prostatectomy and 96 had adequate pathological staging data available for review and correlation. Pathological staging revealed pT2a cancers in 26%, pT2b in 53%, pT3a in 19%, pT3b and pT0 in 1% of patients. This distribution indicated that the unstageable cohort correlated most precisely with clinical stage T1c (r = 0.99). CONCLUSIONS: Thus, the prevalence of unstageable prostate cancer is low but significant and it can be accurately classified into clinical stage T1c.     

An implant releasing the gonadotropin hormone-releasing hormone agonist histrelin maintains medical castration for up to 30 months in metastatic prostate cancer

PURPOSE: The administration of gonadotropin hormone-releasing hormone agonists is well established for treating metastatic prostate cancer. In an ongoing study we evaluated the effect of a long acting implant that releases the gonadotropin hormone-releasing hormone agonist histrelin ([ImBzl]D-His6,Pro9-Net) in 15 patients with disseminated prostate cancer. MATERIALS AND METHODS: The 2.6 cm. implant releasing 60 microg. histrelin daily is inserted subcutaneously into the upper arm using local anesthesia. Of the patients 8 received 1 and the remainder received 2 implants. Treatment with the antiandrogen flutamide or cyproterone acetate began 2 weeks before implant insertion and continued for up to 12 weeks. Testosterone, luteinizing hormone (LH) and prostate specific antigen were determined monthly, and a metastatic evaluation was performed every 6 months. RESULTS: LH and testosterone increased after flutamide administration and decreased after implant insertion. By day 28 LH and testosterone were completely suppressed. LH and testosterone decreased immediately after cyproterone acetate administration. Prostate specific antigen began to decrease during antiandrogen therapy and decreased further after implant insertion. One patient requested implant removal after 1 year for personal reasons and 1 died of an unrelated cause 18 months after insertion. Escape was demonstrated in 4 cases at 5, 10, 12 and 19 months, although LH and testosterone remained suppressed. Duration of treatment in the remaining 9 patients was between 21 and 30 months. LH and testosterone remained completely suppressed and prostate specific antigen levels were in the normal range. The clinical and biochemical response was identical in those who received 1 or 2 implants. At 12 months 8 patients were challenged at intermittent intervals for up to 24 months with a bolus of 100 microg. gonadotropin hormone-releasing hormone followed by 2 weeks of flutamide. The response was compared with that in untreated controls recently diagnosed with prostate cancer. Unlike controls there was complete LH suppression in the 8 challenged patients. CONCLUSIONS: A histrelin implant suppresses LH and testosterone in prostate cancer for up to 30 months. This finding represents a significant improvement over existing preparations, which must be administered at 1 to 3-month intervals.     

Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy

PURPOSE: Computerized tomography (CT) of the abdomen and pelvis is often routine in the preoperative staging assessment of invasive transitional cell carcinoma of the bladder. We determine the accuracy of staging CT findings, usefulness before planned extirpative surgery and impact on surgical management of this disease. MATERIALS AND METHODS: We retrospectively reviewed the medical records, including radiographic, operative and pathological reports, of 82 consecutive cases. All patients presented with muscle invasive bladder tumors, were considered candidates for radical cystectomy and underwent preoperative staging CT of the abdomen and pelvis between July 1994 and June 1998. The ability of CT to provide additional staging information in terms of depth of tumor invasion, local extent of tumor, pelvic lymph node involvement and distant metastases was examined. We determined whether CT findings altered surgical management for individual patients. RESULTS: CT was able to discriminate depth of invasion in only 1 patient (1.2%) and correctly identified extravesical tumor spread in 4 (4.9%). Lymph node and distant metastases were accurately determined in 4 (4.9%) and 2 (2.4%) cases, respectively. The overall accuracy of CT was 54. 9%, with an under staging and over staging rate of 39.0% and 6.1%, respectively. CT provided accurate, additional staging information in only 8 cases (9.8%). Surgical management was altered in 3 cases (3.7%) and only 1 (1.2%) avoided an unnecessary operation as a result of CT findings. CONCLUSIONS: Staging CT of the abdomen and pelvis in patients with invasive bladder carcinoma has limited accuracy, mainly because of its inability to detect microscopic or small volume extravesical tumor extension and lymph node metastases. CT tends to under stage advanced disease and failed to alter surgical management in nearly all of our cases.     

The role of radical surgery for renal cell carcinoma with extension into the vena cava

PURPOSE: New operative technologies, such as the bypass procedures that have become established in the last decade, have led to improved prognosis in patients with renal cell carcinoma and vena caval thrombi. We report the outcome of stage dependent surgical strategies in patients with renal cell carcinoma extending into the vena cava. MATERIALS AND METHODS: From January 1987 to August 1998, 93 patients with renal cell carcinoma invading the inferior vena cava were seen at our institution. Of the patients 79 underwent radical nephrectomy, phlebotomy and thrombus extraction, including 74 who underwent surgical treatment with cardiopulmonary bypass and deep hypothermic circulatory arrest. In 2 patients with retrohepatic thrombi we placed a pump driven femoro-axillary shunt during surgical resection of the retrohepatic tumor portion. RESULTS: Distant metastases and lymph node involvement proved to be highly significant prognostic factors for survival, while the cranial extent of the tumor thrombi had no prognostic impact. Patients without distant metastases had a 5-year survival rate of 34%, which improved to 39% if regional lymph nodes were not involved. There were 5 perioperative deaths (6.3%) and the highest perioperative mortality rate (40%) was seen in patients with supradiaphragmatic thrombi. CONCLUSIONS: Radical surgery for renal cell carcinoma extending to the vena cava is justified when the tumor thrombus does not extend beyond the level of the diaphragm in the cranial direction. In view of the high perioperative mortality decisions about radical surgery must be made individually in patients with level IV thrombi, even if long-term survival is possible.     

Model to predict if a vasoepididymostomy will be required for vasectomy reversal

PURPOSE: We devised a model to predict, preoperatively, the need for a vasoepididymostomy (VE) when performing a vasectomy reversal. Urologists could use it to identify those patients who need a referral to an experienced VE surgeon. MATERIALS AND METHODS: We performed a retrospective review of 483 patients who underwent vasectomy reversal by a single surgeon (AJT) including 393 vasovasostomies and 90 vasoepididymostomies. Selection was based on chart availability. Established criteria were used in deciding the type of reversal (eg gross appearance and microscopic examination of vasal fluid). Type of reversal, patient age and time since vasectomy were recorded. Univariate analysis revealed that patient age (p <0.001) and time since vasectomy (p <0.001) were significant predictors of reversal type. On multivariate logistic regression analysis, time since vasectomy (p <0.001) was the only significant independent predictor. We designed a linear regression algorithm based on time since vasectomy and patient age to predict if a VE would be performed. The model was designed using 433 patients and then tested on a separate randomly selected 50 patient group. The model was designed to be 100% sensitive in detecting patients requiring VE. RESULTS: In the test group the model was 100% sensitive in predicting VE with a specificity of 58.8%. The area under the ROC curves for the design and test groups was 0.8. Palm (PalmSource Inc., Sunnyvale, California) and Windows (Microsoft Corporation, Redmond, Washington) versions are available as free shareware from www.uroengineering.com. CONCLUSIONS: The model is 100% sensitivity in detecting those patients who may require a VE during vasectomy reversal (specificity of 58.8%). It may allow urologists to preoperatively identify these patients.     

Independent validation of the 2002 American Joint Committee on cancer primary tumor classification for renal cell carcinoma using a large, single institution cohort

PURPOSE: The primary tumor classification for renal cell carcinoma (RCC) was updated by the American Joint Committee on Cancer in 2002. To date the new classification has not been validated using an independent group of patients and, therefore, its accuracy for predicting patient outcome is unknown. In the current study we evaluated the 2002 primary tumor classification and compared its predictive ability with that of the 1997 classification. MATERIALS AND METHODS: We studied 2,746 patients treated with radical nephrectomy or nephron sparing surgery for unilateral, sporadic RCC between 1970 and 2000. Cancer specific survival was estimated using the Kaplan-Meier method. The predictive abilities of the 1997 and 2002 classifications were compared using the concordance index. RESULTS: There were 812 deaths from RCC a mean of 3.3 years following nephrectomy. Median followup in patients still alive at last followup was 9 years. Estimated 5-year cancer specific survival rates by the 2002 tumor classification were 97%, 87%, 71%, 53%, 44%, 37% and 20% in patients with pT1a, pT1b, pT2, pT3a, pT3b, pT3c and pT4 RCC, respectively. The concordance index for the association between the 2002 classification and death from RCC was 0.752 compared with 0.737 for the 1997 classification, indicating that the 2002 version contained more predictive ability. CONCLUSIONS: Our data suggest that the 2002 primary tumor classification with pT1 cancers subclassified into pT1a and pT1b provides excellent stratification of patients according to cancer specific survival and it has a predictive ability that is superior to that of the 1997 classification.