Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses

PURPOSE: We compared histological subtype, pathological features and outcome of patients with solid renal masses who were 18 to 40 years old vs patients who were 60 to 70 years old. MATERIALS AND METHODS: We conducted a retrospective review of the Mayo Clinic Nephrectomy Registry from 1970 to 2000, and identified 124 patients 18 to 40 years old and 1,067 patients 60 to 70 years old available for analysis. RESULTS: There was no significant difference in the incidence of benign solid renal masses between patients 18 to 40 years old and those 60 to 70 years old (13.7% vs 10.2%). Among patients with renal cell carcinoma (RCC), younger patients were more likely to have chromophobe RCC (13.1% vs 3.6%) and less likely to have clear cell RCC (70.1% vs 81.5%) than older patients. Among patients with clear cell RCC, younger patients were more likely to have stage pT2b or lower tumors (82.7% vs 69.9%) and a higher incidence of cystic clear cell RCC (10.7% vs 2.2%) than older patients. Younger patients had an improved cancer specific survival compared with older patients but this difference was not statistically significant (risk ratio 0.71, p =0.127). CONCLUSIONS: We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.     

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.     

Prognostic value of multifocality on progression and survival in localized renal cell carcinoma

OBJECTIVE: Incidence of multifocality in Renal Cell Carcinoma (RCC) is estimated at between 5 and 25%. Multifocality has been largely studied because of the growing interest in conservative surgery which is a risk of local recurrence. The aim of this study is to evaluate the relationship between multifocality and other prognostic parameters and whether it is an independent prognostic factor. MATERIAL AND METHODS: From 1980 to 1990, 255 patients (median age: 60.9 years) were treated by radical nephrectomy for pT1 to pT3b N0M0 RCC. The median follow-up time was 183 months. Multifocality was defined as the existence of at least one other tumoral localization, macroscopically and microscopically diagnosed as renal cell carcinoma, in the same kidney. Studied parameters were: age, sex, side, size, stage, Fuhrman's grade, capsular invasion, renal vein involvement and microvascular invasion. Survival was assessed with Kaplan-Meier and Cox models. RESULTS: 37 cases of multifocal RCC were diagnosed (14.5%). There was only a significant correlation with stage (p=0.002) and with capsular invasion (p=0.002). No other factor was correlated with multifocality. It had no influence on the risk of metastatic progression, overall or specific survival. CONCLUSION: There is a significant correlation between capsular invasion and multifocality that has to be considered before proposing conservative surgery for a localized RCC. Multifocality has no influence on survival or metastatic progression in case of radical nephrectomy.     

pT2 classification for renal cell carcinoma. Can its accuracy be improved?

PURPOSE: The 2002 tumor classification for renal cell carcinoma (RCC) classifies pT2 tumors as more than 7 cm in greatest dimension, limited to the kidney. In this study we determined whether a size cutoff point exists within pT2 tumors and whether such subclassification would further improve the accuracy of the current tumor classification. MATERIALS AND METHODS: We studied 544 patients with unilateral, sporadic pT2 RCC treated with radical nephrectomy or nephron sparing surgery between 1970 and 2000. The association of tumor size with death from RCC was examined using martingale residuals from a Cox proportional hazards regression model to determine the optimal size cutoff point. RESULTS: There were 204 deaths from RCC a median of 3.8 years following nephrectomy. Univariately tumor size was significantly associated with death from RCC (risk ratio 1.08, 95% CI 1.04 to 1.13, p <0.001). A scatterplot of tumor size vs expected risk of death per patient suggested that a cutoff point between 9 and 10 cm was appropriate. When adjusted for regional lymph node involvement and distant metastases, the 10 cm cutoff point performed better than the 9 cm point (risk ratio 1.42, 95% CI 1.07 to 1.90, p = 0.017 vs 1.22, 95% 0.86 to 1.72, p = 0.268). Therefore, we propose using a 10 cm cutoff point to subclassify patients into pT2a and pT2b. CONCLUSIONS: Our data suggest that the prognostic accuracy of the 2002 pT2 tumor classification can be further improved by subclassifying patients with tumors greater than 7 and less than 10 cm into a pT2a category, and those with tumors 10 cm or greater into a pT2b category.     

Multiple ipsilateral renal tumors discovered at planned nephron sparing surgery: importance of tumor histology and risk of metachronous recurrence

PURPOSE: Unrecognized sporadic multifocality at planned nephron sparing surgery (NSS) presents a surgical dilemma. We report a single institution experience with patients presenting with multiple ipsilateral renal tumors, of which at least 1 was renal cell carcinoma (RCC). We determined the outcome for patients treated with NSS or radical nephrectomy (RN). MATERIALS AND METHODS: A total of 118 patients underwent surgery between 1970 and 2000 for sporadic multiple ipsilateral renal tumors, of which at least 1 was RCC. The patients were treated with RN (102) and NSS (16). Clinical features recorded included age at surgery, sex, history of smoking, a preexisting solitary kidney and symptomatic disease at presentation. Pathological features included histological subtype, nuclear grade, tumor stage (2003 TNM) and tumor size. Cancer specific survival was estimated using the Kaplan-Meier method. RESULTS: A greater proportion of patients treated with NSS had a solitary kidney compared with patients treated with RN (6 or 38% versus 0, p <0.001). Of the 102 patients treated with RN for multiple tumors 12 died of RCC at a median time to death of 3.3 years (range 3 months to 9.5 years). Estimated cancer specific survival at 5 years was 90.1%. There was metachronous contralateral recurrence in 5 patients a median of 8.1 years following RN (range 3 months to 14 years). Two of the 16 patients treated with NSS died of RCC 6 and 11 years following NSS, respectively, for a cancer specific survival rate of 100% at 5 years. Two patients had local renal recurrence 1.7 and 2.8 years following NSS, respectively, and a metachronous contralateral renal tumor was found in 1 patient 7 months following NSS. Of the 102 patients treated with RN 63 (62%) and 9 of the 16 (56%) treated with NSS had at least 1 clear cell RCC. In 23 of the 102 patients (23%) treated with RN only 1 tumor was RCC, while the remainder were benign, suggesting that these patients were potential candidates for NSS. CONCLUSIONS: Patients undergoing RN or NSS for multiple ipsilateral renal tumors, of which at least 1 is RCC, have favorable cancer specific survival. The metachronous contralateral recurrence rate for patients with sporadic multifocal lesions is approximately 5%. Planned NSS may not be abandoned if satellite lesions are benign.     

Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States

Renal cell carcinoma (RCC) is a common malignancy following kidney transplantation. We describe RCC risk and examine RCC risk factors among US kidney recipients (1987–2010). The Transplant Cancer Match Study links the US transplant registry with 15 cancer registries. Standardized incidence ratios (SIRs) were used to compare RCC risk (overall and for clear cell [ccRCC] and papillary subtypes) to the general population. Associations with risk factors were assessed using Cox models. We identified 683 RCCs among 116 208 kidney recipients. RCC risk was substantially elevated compared with the general population (SIR 5.68, 95% confidence interval 5.27–6.13), especially for papillary RCC (SIR 13.3 versus 3.98 for ccRCC). Among kidney recipients, RCC risk was significantly elevated for blacks compared to whites (hazard ratio [HR] 1.50) and lower in females than males (HR 0.56). RCC risk increased with prolonged dialysis preceding transplantation (p‐trend < 0.0001). Risk was variably associated for RCC subtypes with some medical conditions that were indications for transplantation: ccRCC risk was reduced with polycystic kidney disease (HR 0.54), and papillary RCC was increased with hypertensive nephrosclerosis (HR 2.02) and vascular diseases (HR 1.86). In conclusion, kidney recipients experience substantially elevated risk of RCC, especially for papillary RCC, and multiple factors contribute to these cancers.     

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

Background: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was preformed to assess the accuracy of pre-and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions.Materials and methods: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand.Results: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard.Conclusions: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.CommentaryLocal tumor recurrence following nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) may be due to incomplete resection of the primary tumor, occult multicentric disease or the development of a new primary or metastatic focus of RCC in the renal remnant. The risk of multicentric disease in RCC has been evaluated and debated extensively in the literature. RCC generally occurs as a discrete focal lesion rather than an infiltrative process which is seen in carcinoma of the prostate. At issue is whether the molecular events that give rise to malignant transformation affect a discrete segment of the kidney or a broader segment of the renal tubular epithelium. A high incidence of multicentric RCC has been reported in patients with germ line mutations such as those that exist in von Hippel Lindau disease and other forms of hereditary RCC suggesting a global predisposition to malignant degeneration throughout the entire renal parenchyma.The incidence of multicentricity in sporadic RCC has been less clear. Emerging cytogenetic and molecular data suggest that satellite lesions may occasionally arise from the same malignant clone as their corresponding primary lesion and may therefore represent biologically significant intra-renal metastasises. A recent review of published studies comprising over 1100 cases of sporadic RCC indicated an aggregate incidence of 15.2% of tumor multifocality (range 6.5%–28%)[1]. It is important to remember that these studies represent a diverse group of patients and that RCC is in fact a heterogenous group of tumors. The risk of multicentricity is not equal in all patients and appears to be related to other prognostic variables such as tumor histology, stage and grade. For example, papillary RCC is known to be associated with a higher incidence of multifocality than the more common clear cell variant. The risk of multifocal disease also increases with larger tumors, particularly those that extend beyond the renal capsule (pT3+). Finally, some microfocal tumors are of unknown biological significance such as the finding of satellite adenomas. Of importance when considering relative indications for elective NSS is the incidence of multifocality when the primary or index tumor is ⩽ 4 cm. A recent review of the literature indicated that the incidence of multifocality in this setting is approximately 5%.The most worrisome implication of multifocal RCC is that this will predispose to an increased risk of local tumor recurrence following NSS. Although this potential risk must be considered, the relationship between multifocality and local recurrence is neither linear or predictable as suggested by the low overall local recurrence rates reported following NSS in several large series. In nearly 1800 cases of NSS reported in the literature to date, the risk of local tumor recurrence has ranged from 0–10% and is clearly lowest among patients undergoing elective NSS for small (⩽ 4 cm) low stage lesions [1]. The true biologic significance of multicentric renal tumors and their implication for NSS therefore remain to be fully elucidated.[1] Uzzo RG, Novick AC. Nephron-sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18.Andrew C. Novick, M.D.     

Matched comparison of radical nephrectomy vs. nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney.

Objective: To report the long-term follow-up of a matched comparison of radical nephrectomy (RN) and nephron-sparing surgery (NSS) in patients with single unilateral renal cell carcinoma (RCC) and a normal contralateral kidney.Patients and Methods: Between August 1966 and March 1999, 1492 and 189 patients with unilateral RCC and a normal contralateral kidney underwent RN and NSS, respectively. Patients with renal impairment, previous nephrectomy, bilateral or multiple RCCs, metastasis, and familial cancer syndromes were excluded. A total 164 patients in each cohort were matched according to pathological grade, pathological T stage, size of tumor, age, sex, and year of surgery. The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate and compare overall, cancer-specific, local recurrence-free, and metastasis-free survival and survival free of chronic renal insufficiency. The 2 groups were evaluated for early (⩽30 days) complications and proteinuria at last follow-up.Results: At last follow-up, 126 RN patients (77%) and 130 NSS patients (79%) were alive with no evidence of disease. There was no significant difference observed between patients who had RN and those who had NSS with respect to overall survival (risk ratio, 0.96; 95% confidence interval [CI], 0.52–1.74; P = .88) or cancer-specific survival (risk ratio, 1.33; 95% CI, 0.30–5.95; P = .71). At 10 years, similar rates of contralateral recurrence (0.9% for RN vs 1% for NSS) and metastasis (4.9% for RN vs 4.3% for NSS) were seen in each group, whereas the rate of ipsilateral local recurrence for patients who underwent RN and NSS was 0.8% and 5.4%, respectively (P = .18). There was no significant difference in the early complications between the RN and NSS groups. However, patients who underwent RN had a significantly higher risk for proteinuria as defined by a protein/osmolality ratio of 0.12 or higher (55.2% vs 34.5%; P = .01). At 10 years, the cumulative incidence of chronic renal insufficiency (creatinine > 2.0 mg/dL at least 30 days after surgery) was 22.4% and 11.6%, respectively, for the RN and NSS groups (risk ratio, 3.7; 95% CI, 1.2–11.2; P = .01).Conclusions: This retrospective study of patients with unilateral RCC and a normal contralateral kidney suggests that NSS is as effective as RN for the treatment of RCC on long-term follow-up. The increased risk of chronic renal insufficiency and proteinuria after RN supports use of NSS.CommentaryData from several studies have shown that nephron-sparing surgery (NSS) and radical nephrectomy provide equally effective curative treatment for patients with a single, small (⩽ 4 cm), unilateral, localized renal cell carcinoma (RCC) and a normal opposite kidney 1, 2. A recent study from Memorial Sloan Kettering reported a 10-year cancer free survival rate of 97% following elective partial nephrectomy in 70 such patients [3]. Other studies have further shown that the cost of NSS is equivalent to that of radical nephrectomy [4] and that quality of life is improved following NSS in this setting [5].Notwithstanding the above data, there has been controversy concerning the renal functional advantage of performing NSS when the contralateral kidney is anatomically and functionally normal. Long-term follow-up after live donor nephrectomy operations has failed to demonstrate any significant adverse sequela in terms of proteinuria, hypertension or renal failure. However, patients undergoing surgical treatment for localized RCC represent a different population who are generally older and often have co-morbid medical conditions. This is the likely explanation for the findings in this important study from the Mayo Clinic which suggest an increased risk of chronic renal insufficiency and proteinuria after radical nephrectomy (compared to NSS) in patients with a normal contralateral kidney. A similar observation was recently reported in a study from Memorial Sloan Kettering presented at the 2001 annual AUA meeting. These emerging beneficial renal functional data enhance the argument in favor of elective NSS in patients with a solitary small (⩽ 4 cm) RCC and a normal contralateral kidney.Andrew C. Novick, M.D.     

Urethral tumor recurrence following cystectomy and urinary diversion: clinical and pathological characteristics in 768 male patients

PURPOSE: We evaluated the incidence and risks of urethral recurrence following radical cystectomy and urinary diversion in men with transitional cell carcinoma of the bladder. MATERIAL AND METHODS: Clinical and pathological results were evaluated in 768 consecutive male patients undergoing radical cystectomy with intent to cure for bladder cancer with a median followup 13 years, including 397 (51%) who underwent orthotopic urinary diversion with a median followup of 10 years and 371 (49%) who underwent cutaneous urinary diversion with a median followup of 19 years. Demographically and clinically these 2 groups were well matched with the only exception being longer median followup in the cutaneous group (p <0.001). Urethral recurrence was analyzed by univariate and multivariable analysis according to carcinoma in situ, tumor multifocality, pathological characteristics (tumor grade, stage and subgroup), the presence and extent of prostate tumor involvement (superficial vs stromal invasion) and the form of urinary diversion (cutaneous vs orthotopic). RESULTS: A total of 45 patients (6%) had urethral recurrence at a median of 2 years (range 0.2 to 13.6), including 16 (4%) with an orthotopic and 29 (8%) with a cutaneous form of urinary diversion. Carcinoma in situ and tumor multifocality were not significantly associated with an increased risk of urethral recurrence (p = 0.07 and 0.06, respectively). The presence of any (superficial and/or stromal invasion) prostatic tumor involvement was identified in 129 patients (17%). Prostate tumor involvement was associated with a significantly increased risk of urethral recurrence (p = 0.01). The estimated 5-year chance of urethral recurrence was 5% without any prostate involvement, increasing to 12% and 18% with superficial and invasive prostate involvement, respectively. Patients undergoing orthotopic diversion demonstrated a significantly lower risk of urethral recurrence compared with those undergoing cutaneous urinary diversion (p = 0.02). Patients without any prostate tumor involvement and orthotopic diversion (lowest risk group) demonstrated an estimated 4% year chance of urethral recurrence compared with a 24% chance in those with invasive prostate involvement undergoing cutaneous diversion (highest risk group). On multivariate analysis any prostate involvement (superficial and/or invasive) and urinary diversion form remained independent and significant predictors of urethral recurrence (p = 0.035 and 0.01, respectively). CONCLUSIONS: At long-term followup urethral tumor recurrence occurs in approximately 7% of men following cystectomy for bladder transitional cell carcinoma. Involvement of the prostate with tumor and the form of urinary diversion were significant and independent risk factors for urethral tumor recurrence. Patients undergoing orthotopic diversion have a lower incidence of urethral recurrence compared with those undergoing cutaneous diversion. Although prostate tumor involvement is a risk factor for urethral recurrence, it should not preclude orthotopic diversion, provided that intraoperative frozen section analysis of the urethral margin is without evidence of tumor.     

Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system

PURPOSE: We created an evidence based postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma (RCC) based on a risk group stratification system. MATERIALS AND METHODS: 559 patients undergoing surgery for localized and ocally advanced RCC were stratified into low risk (LR), intermediate risk (IR) and high risk (HR) groups based on the University of California-Los Angeles Integrated Staging System (UISS). Tumor recurrences were identified and categorized according to time and location. RESULTS: Patients with localized disease had a lower 5-year recurrence rate than patients with locally advanced (nodal) disease (27.6% vs 64%, p <0.0001). Patients in the LR, IR, and HR groups following nephrectomy demonstrated 5-year recurrence-free rates of 90.4%, 61.8%, and 41.9%, respectively (p <0.0001), and median times to recurrence of 28.9, 17.8 and 9.5 months, respectively (p <0.0001). Chest and abdomen recurrences comprised of 75% and 37.5%, 77.4% and 58.1%, and 45.2% and 67.7% of recurrences in the LR, IR and HR groups, respectively. In patients with node positive disease, chest and abdomen comprised of 58.8% and 76.5% of recurrences, respectively. Patients undergoing partial nephrectomy did not demonstrate a greater rate of local or distant recurrence compared with patients undergoing radical nephrectomy. CONCLUSIONS: Significant differences in incidence and time to recurrence following surgical resection for RCC mandates unique surveillance protocols for patients in each of the UISS risk groups. LR group patients should be followed for at least 5 years, whereas IR and HR group patients require longer surveillance. HR group patients require more stringent abdominal surveillance, whereas LR group patients should emphasize the chest. Patients with nodal disease also require stringent followup. Patients undergoing partial nephrectomy for localized disease can be followed according to the same UISS risk group based protocol.     

p53 is an independent predictor of tumor recurrence and progression after nephrectomy in patients with localized renal cell carcinoma

PURPOSE: We determined which clinical and molecular variables can predict cancer recurrence in patients following surgical management for localized renal cell carcinoma (RCC). MATERIALS AND METHODS: From a custom kidney cancer tissue microarray containing tumors specimens from 350 patients 193 undergoing nephrectomy for localized RCC at our institution between 1989 and 2000 were identified. The array was then analyzed by immunohistochemistry for certain molecular markers, namely CA9, CA12, Ki67, gelsolin, p53, EpCAM, pTEN and vimentin. The medical records of these patients were then reviewed for age, sex, TNM stage, tumor size, nuclear grade, Eastern Cooperative Oncology Group (ECOG) performance status, recurrence status and, when applicable, time to recurrence. Cox regression analyses were done to determine clinical and molecular predictors of time to tumor recurrence. RESULTS: Of the patients 15% demonstrated evidence of tumor recurrence following nephrectomy (29 of 193). Univariate Cox regression demonstrated that tumor size, T stage, grade, ECOG performance status, Ki67, EpCAM and p53 were significantly associated with recurrence (p <0.05). A multivariate Cox regression model showed that T stage (p = 0.018), ECOG (p = 0.004) and p53 (p = 0.003) were the 3 most significant predictors. p53 expression correlated significantly with nuclear grade (Pearson correlation 0.22, p = 0.023) but not with any other clinical factors. Patients with localized tumors demonstrating mean p53 staining values above and below 20% of cells had recurrence rates of 37.7% and 14.4%, respectively (RR = 3.28, p = 0.018). CONCLUSIONS: p53 is a significant molecular predictor of tumor recurrence, as identified in patients undergoing treatment for localized RCC.     

Predicting Occult Multifocality of Renal Cell Carcinoma

Background

Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up.

Objective

Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC.

Design, setting, and participants

We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties.

Interventions

All patients underwent radical nephrectomy.

Measurements

Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms.

Results and limitations

The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively.

Conclusions

Our data suggest that occult multifocal RCC is more frequently associated with small (2–4 cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables.     

Sarcomatoid renal cell carcinoma: an examination of underlying histologic subtype and an analysis of associations with patient outcome

A sarcomatoid component can occur in all histologic subtypes of renal cell carcinoma (RCC) and indicates an aggressive tumor. We studied 2381 patients treated with radical nephrectomy for RCC between 1970 and 2000. A urologic pathologist reviewed the microscopic slides from all tumor specimens for the presence of a sarcomatoid component, defined as a RCC with any malignant spindle cell component. All tumors with a sarcomatoid component were classified as nuclear grade 4. A total of 120 (5.0%) patients had RCC with a sarcomatoid component, including 94 who died of RCC at a mean of 1.4 years following nephrectomy (median 8 months; range 44 days to 10 years). Cancer-specific survival rates at 2 and 5 years following nephrectomy were 33.3% and 14.5%, respectively. The presence of distant metastases at the radical nephrectomy and histologic tumor necrosis were significantly associated with death from RCC among patients with sarcomatoid RCC. Patients with clear cell (conventional) RCC and chromophobe RCC were more likely to have tumors with a sarcomatoid component (5.2% and 8.7%, respectively) compared with patients with papillary RCC (1.9%). The presence of a sarcomatoid component was significantly associated with death from RCC for all three subtypes (P < 0.001). Even among patients with grade 4 clear cell RCC, the presence of a sarcomatoid component was significantly associated with outcome, both univariately (risk ratio 1.59; P = 0.010) and after adjusting for TNM stage, tumor size, and histologic tumor necrosis (risk ratio 1.46; P = 0.037).     

Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma

Our objective was to compare cancer-specific survival and to examine associations with outcome among the histologic subtypes of renal cell carcinoma (RCC). We studied 2385 patients whose first surgery between 1970 and 2000 was a radical nephrectomy for sporadic, unilateral RCC. All RCC tumors were classified following the 1997 Union Internationale Contre le Cancer and American Joint Committee on Cancer guidelines. There were 1985 (83.2%) patients with clear cell, 270 (11.3%) with papillary, 102 (4.3%) with chromophobe, 6 (0.3%) with collecting duct, 5 (0.3%) with purely sarcomatoid RCC and no underlying histologic subtype, and 17 (0.7%) with RCC, not otherwise specified. Cancer-specific survival rates at 5 years for patients with clear cell, papillary, and chromophobe RCC were 68.9%, 87.4%, and 86.7%, respectively. Patients with clear cell RCC had a poorer prognosis compared with patients with papillary and chromophobe RCC (p <0.001). This difference in outcome was observed even after stratifying by 1997 tumor stage and nuclear grade. There was no significant difference in cancer-specific survival between patients with papillary and chromophobe RCC (p = 0.918). The 1997 TNM stage, tumor size, presence of a sarcomatoid component, and nuclear grade were significantly associated with death from clear cell, papillary, and chromophobe RCC. Histologic tumor necrosis was significantly associated with death from clear cell and chromophobe RCC, but not with death from papillary RCC. Our results demonstrate that there are significant differences in outcome and associations with outcome for the different histologic subtypes of RCC, highlighting the need for accurate subtyping.     

Predicting postoperative renal insufficiency in patients undergoing nephrectomy for renal malignancy: assessment by renal scintigraphy using 99mtechnetium-mercaptoacetyltriglycine

PURPOSE: We performed Tc-mercaptoacetyltriglycine (MAG3) renal scintigraphy in patients with renal malignancy to evaluate the function of each renal unit before and after nephrectomy to see if postoperative functional deterioration could be predicted based on scintigraphy results and creatinine clearance. MATERIALS AND METHODS: A total of 22 men and 13 women with renal malignancy, including 32 with renal cell carcinoma and 3 with urothelial cancer, were prospectively enrolled in this study. Average patient age was 64.3 years (median 65, range 43 to 88). All patients underwent MAG3 renal scintigraphy before and after unilateral nephrectomy. At the same time serum creatinine and endogenous creatinine clearance were determined. RESULTS: Mean serum creatinine was 0.93 mg/dl before and 1.31 after nephrectomy (p <0.0001). Preoperative endogenous creatinine clearance was 70.8 ml per minute per 1.73 m, which decreased to 49.0 ml per minute per 1.73 m after nephrectomy (p <0.0001). Mean MAG3 clearance of the remaining kidney increased 35.1% above baseline from 156.5 to 211.5 ml per minute per 1.73 m following nephrectomy. Spearman rank core analysis revealed that preoperative MAG3 clearance of the remaining kidney significantly correlated with postoperative creatinine clearance (r = 0.596, p = 0.0005). Preoperative MAG3 clearance of the remaining kidney more than 130 ml per minute per 1.73 m coincided with postoperative creatinine clearance above 40 ml per minute per 1.73 m. CONCLUSIONS: MAG3 renal scintigraphy may be useful for predicting renal insufficiency after nephrectomy. The findings in this study suggest that preoperative MAG3 clearance of the remaining kidney less than 130 ml per minute per 1.73 m is a risk factor for postoperative renal insufficiency.     

Incidental renal cell carcinoma and nephron sparing surgery

The role of nephron sparing surgery in patients with a solitary kidney, bilateral kidney tumors or an impaired renal function has been widely accepted. Partial nephrectomy in patients with a normal contralateral kidney is still under discussion. Nevertheless, more and more surgeons perform nephron sparing surgery in these patients with good results. From historical comparisons there seems to be no statistically significant difference in five-year survival between radical nephrectomy and nephron sparing surgery when the tumor diameter is four centimeters or less. The most common problem is the risk of tumor recurrence due to the multifocality. However, multifocality is more frequent than kidney recurrence, questioning the spontaneous evolution of satellite lesions. Further investigations are necessary to optimize patient selection. Therefore, a randomized prospective multicenter study with long-term follow-up might add to the excellent results published by several authors during the last two years in order to confirm that nephron sparing surgery is an excellent alternative to radical nephrectomy in small asymptomatic renal cell carcinoma.     

Assessment of surgical margins in renal cell carcinoma after nephron sparing: a comparative study: laparoscopy vs open surgery

PURPOSE: We compared the status of the peritumoral parenchyma after open and laparoscopic nephron sparing surgery for renal cell carcinoma. MATERIALS AND METHODS: The records of 64 consecutive patients who underwent nephron sparing surgery for renal cell carcinoma of 4 cm or less were reviewed retrospectively. Patients in group 1 underwent open retroperitoneal surgery (1998 to 2000) and patients in group 2 underwent laparoscopic (transperitoneal or retro peritoneal) surgery (2001 to March 2004). A single pathologist was employed to analyze the specimens, and comparative analysis included examination of tumor size, weight, histological cell type, intraoperative histological biopsies and margin status. RESULTS: The 2 groups were comparable in terms of clinical data, and mean lesion size was 31.4 mm in group 1 and 32 mm in group 2. Positive margins were found in 1 of 30 patients in group 1 and in 1 of 34 in group 2 (p = 0.9). An analysis of margins was performed by taking measurements at the minimum and maximum points of the section. The minimum mean measurement was 2 mm in group 1 and 2.08 mm in group 2 (p = 0.75). The maximum mean measurement was 4.56 mm in group 1 and 5.2 mm in group 2 (p = 0.09). The difference between minimum and maximum margin thickness was 2.56 mm in group 1 and 3.16 mm in group 2 (p = 0.04). Mean followup for group 1 was 50 months (range 30 to 72) and 16 months (range 2 to 35) for group 2. One local recurrence was recorded in group 1 and treated with radical nephrectomy, while no recurrence was recorded in group 2. CONCLUSIONS: In this study we further confirmed the efficiency of resectioning lesions using laparoscopy. In our experience there is no difference between the 2 procedures in terms of efficient surgical margins. However, despite these encouraging results it is necessary to obtain more extensive followup data, which will allow us to be more specific in reporting on laparoscopic margin quality.     

Surgical management of renal tumors 4 cm. or less in a contemporary cohort

PURPOSE: We evaluated a patient cohort with renal tumors 4 cm. or less treated with partial or radical nephrectomy. We compared patient and tumor characteristics, and survival in these 2 groups. MATERIALS AND METHODS: We retrospectively analyzed the records of 670 patients with a median age of 63 years treated surgically for renal cell carcinoma between July 31, 1989 and July 31, 1997. Renal tumors 4.0 cm. or less were noted in 252 patients (38%) who underwent a total of 262 procedures, including 183 radical (70%) and 79 partial (30%) nephrectomies. Ten patients required 2 operations each because of bilateral renal cell carcinoma. Median followup was 40 months. We compared clinicopathological parameters in the partial and radical nephrectomy groups using chi-square or Wilcoxon analysis as appropriate. Survival analysis was determined by the log rank test and Cox regression model. RESULTS: The partial and radical nephrectomy groups were comparable with respect to gender ratio, tumor presentation, histological classification, pathological stage and complication rate. Median tumor size was 2.5 and 3.0 cm. in the partial and radical nephrectomy groups, respectively (p = 0.0001). Resection was incomplete in 1 patient (1.3%) in the partial and none in the radical nephrectomy group. There was no local recurrence after either procedure, and no significant difference in disease specific, disease-free and overall survival (p = 0.98, 0.23 and 0.20, respectively). CONCLUSIONS: Patients with a small renal tumor have similar perioperative morbidity, pathological stage and outcome regardless of treatment with partial or radical nephrectomy. Therefore, partial nephrectomy remains a safe alternative for tumors of this size.     

Unusual presentation of late recurrence renal malignancy

Introduction

Late recurrence of renal cell carcinoma is rare and mostly of clear cell histology. The objective of our study was to report our case of late recurrence of papillary RCC.

IS FROZEN SECTION ANALYSIS IN NEPHRON SPARING SURGERY NECESSARY? A CLINICOPATHOLOGICAL STUDY OF 301 CASES

PURPOSE: One of the basic principles of nephron sparing surgery for renal cell carcinoma is resection of the tumor with normal tissue margins verified by frozen section analysis. In cases of positive tumor margins the surgeon is committed to complete the local resection or to perform radical nephrectomy. In this study we retrospectively evaluated the yield of frozen section analysis performed during nephron sparing surgeries, especially concerning compatibility with the final histological report and the long-term oncological outcome. MATERIALS AND METHODS: Between 1988 and 2003, 172 men and 129 women with a mean age of 59 years (range 16 to 83) underwent nephron sparing surgery due to suspected renal tumors. Mean tumor size was 3.56 cm (range 1 to 12.5). Frozen section analysis was routinely performed during surgery. RESULTS: Positive tumor margins in frozen section analysis were found in 2 cases (0.7%). In both cases the tumor was centrally located. Those 2 patients underwent immediate radical nephrectomy but no residual tumor was subsequently found in the radical nephrectomy specimens. Paraffin sections disclosed positive tumor margins in 4 other cases (1.3%) in whom the frozen section analysis had shown tumor negative margins. Of the 4 patients 1 underwent radical nephrectomy for tumor recurrence after 9 months. The other 3 patients showed no evidence of disease recurrence after 26, 59 and 120 months of followup. CONCLUSIONS: Our results suggest that frozen section analysis during nephron sparing surgery has minimal clinical significance and hence routine incorporation in urological practice should be reconsidered.