Survival advantage of partial over radical nephrectomy in patients presenting with localized renal cell carcinoma.

BACKGROUND: Partial nephrectomy (PN) preserves renal function and has become the standard approach for T1a renal cell carcinoma (RCC). However, there is still an ongoing debate as to which patients will actually derive greater benefit from partial than from radical nephrectomy (RN). The aim of this study was to retrospectively evaluate the impact of the type of surgery on overall survival (OS) in patients with localized RCC. METHODS: Renal surgery was performed in 4326 patients with localized RCC (pT ≤ 3a N/M0) at six German tertiary care centers from 1980 to 2010: RN in 2955 cases (68.3%), elective (ePN) in 1108 (25.6%), and imperative partial nephrectomy (iPN) in 263 (6.1%) cases. The median follow-up for all patients was 63 months. Kaplan-Meier and Cox regression analyses were carried out to identify prognosticators for OS. RESULTS: PN was performed significantly more often than RN in patients presenting with lower tumor stages, higher RCC differentiation, and non-clear cell histology. Accordingly, the calculated 5 (10)-year OS rates were 90.0 (74.6)% for ePN, 83.9 (57.5)% for iPN, and 81.2 (64.7)% for RN (p < 0.001). However, multivariate analysis including age, sex, tumor diameter and differentiation, histological subtype, and the year of surgery showed that ePN compared to RN still qualified as an independent factor for improved OS (HR 0.79, 95% CI 0.66-0.94, p = 0.008). CONCLUSION: Even allowing for the weaknesses of this retrospective analysis, our multicenter study indicates that in patients with localized RCC, PN appears to be associated with better OS than RN irrespective of age or tumor size.

Long-term results of a prospective randomized trial evaluating G-CSF priming in intensive induction chemotherapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia.

Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy. CR rates with G-CSF priming and G-CSF post-chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS) probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD and NPM mutations and did not improve outcome in patients with adverse cytogenetics. In a landmark analysis, late consolidation with autologous stem cell transplantation or a second consolidation cycle significantly improved RFS compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future studies on G-CSF priming should be restricted to NK AML and used only in post-remission therapy.

Age--an independent prognostic factor of clinical outcome in renal malignancies: results of a large study over two decades.

PURPOSE: Age has been linked to outcome in renal cancer patients, but mainly in North American cohorts. In this study, we hypothesized that age is correlated with metastasis and cancer-specific survival in a German cohort regardless of types of treatments. METHODS: A total of 1,538 patients treated for renal malignancies between 1991 and 2010 were evaluated. Mean age and median age are 61.9 ± 11.6 and 62.6 years. Clinicopathologic [tumor type, size, grade, stage and treatment (surgery, chemotherapy, radiation, immunotherapy)] and outcome parameters (metastasis and survival) were examined for an association with age using logistic regression and Cox proportional hazard model, and Kaplan-Meier plots. RESULTS: Age was associated with stage, metastasis, treatment, cancer-specific and overall mortality (p < 0.01). The metastasis-free and cancer-free survival rates for patients >63 years were lower than those for patients ≤63 years (p < 0.0001). In a multivariate analysis, age was an independent prognostic factor of metastasis, cancer-specific and overall mortality (p < 0.0001) even when data were stratified in different decades and treatment was included as one of the parameters. Patients >63 years of age had 29-35% higher risk of metastasis and cancer-specific mortality than younger patients. Median metastasis-free and cancer-specific survival for patients >63 years of age (months: 84.4; 70.3) was ~50% shorter than in patients ≤63 years (months: 151; 144.6). CONCLUSIONS: This large study shows that, despite advances in surgical and non-surgical treatment modalities over the two decades, age is an independent prognostic indicator of metastasis and cancer-specific mortality in renal cancer patients. Patients >63 years have ~30% increased risk for metastasis and ~50% shorter cancer-specific survival.

Preoperative serum C- reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma.

BACKGROUND: To analyse the prognostic significance of preoperative C-reactive protein (CRP) serum level in patients with upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We evaluated 158 UUT-UC patients who had undergone surgery in the University Hospital of Hannover (MHH). 143 (89.4%) suffered from cancer in the renal pelvis, 13 (8.1%) patients presented with tumour located in the ureter. A preoperative CRP value was available for 115 patients. The mean (median) follow-up for these patients was 28.3 (15.1) months. RESULTS: The median (mean) CRP value of all evaluable patients was 10.0 (40.7) mg/l. The CRP-level, stratified into two subgroups (CRP ≤5 vs. >5 mg/l), correlated significantly with muscle invasive tumour stage (36.4 vs. 78.9%; p<0.001), the risk of presenting nodal disease (4.5 vs. 26.8%; p=0.002) and distant metastasis (2.3 vs. 16.9%; p<0.016). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 54.2 and 26.4% for patients with preoperative CRP levels ≤ and >5 mg/l, respectively (p<0.006). Next to age and the presence of metastasis, multivariate analysis also identified CRP as a continuous variable as an independent prognosticator for CSS. CONCLUSIONS: A high preoperative serum CRP level is associated with locally advanced and metastatic disease in patients with UUT-UC. Its routine use could allow better risk stratification and risk-adjusted follow-up of UUT-UC patients.

High CRP values predict poor survival in patients with penile cancer.

BACKGROUND: High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis. METHODS: This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months. RESULTS: A significantly elevated CRP level (>15 vs. ≤ 15 mg/l) was found more often in patients with an advanced tumor stage (≥pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (≥pT2; HR 8.8, p=0.041) and an elevated CRP value (>15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer. CONCLUSIONS: A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis.

Elevated C-reactive protein values predict nodal metastasis in patients with penile cancer.

BACKGROUND: The nodal status is a strong predictor for cancer specific death in patients with penile carcinoma, and the C-reactive protein (CRP) level at diagnosis has recently been shown to be associated with poor clinical outcome in various solid malignancies. Therefore, this retrospective study was performed to evaluate the association between preoperative CRP levels and the incidence of nodal metastasis in patients with squamous cell carcinoma (SCC) of the penis. METHODS: The analysis included 51 penile cancer patients who underwent either radical or partial penectomy for pT1-4 penile cancer between 1990 and 2010. The nodal status was correlated with patient and tumor specific characteristics. RESULTS: Sixteen (31%) patients had lymph node metastasis at the time of penile cancer surgery. Nodal status was associated with tumor stage but did not correlate significantly with tumor grade. In contrast, high presurgical CRP levels were significantly associated with the diagnosis of nodal involvement (p = 0.04). The optimal CRP cut-off value to predict lymph node metastasis was set at 20 mg/l based on ROC analysis. CONCLUSIONS: Since a high preoperative serum CRP level was closely correlated with nodal disease, it could be used as an additional marker to help identify patients with penile cancer who may benefit from inguinal lymph node dissection.

Does overweight influence the prognosis of renal cell carcinoma? Results of a multicenter study.

OBJECTIVES: To assess the impact of overweight on prognosis of renal cell carcinoma patients. PATIENTS AND METHODS: A total of 2030 patients who underwent surgery for renal cell carcinoma from 1990 to 2011 in three University Medical Centers were included in this retrospective analysis. For all patients, height and weight measurements at the time of diagnosis were available for review. The median (mean) follow up was 56.6 months (66.0 months). RESULTS: A low body mass index was significantly associated with poor tumor differentiation, histology, microscopic vascular invasion and metastatic disease at the time of diagnosis. A lower-than-average body surface area - stratified according to the European average for men (1.98 m(2)) and women (1.74 m(2)) - was significantly related to older age, poor tumor differentiation, the histological subtype and microscopic vascular invasion. In addition, a low visceral fat area calculated in a subgroup of 133 evaluable patients was associated with a higher risk of advanced disease (pT3-4 and/or N/M+) at diagnosis. The tumor-specific 5-year survival rate was 71.3, 78.7 and 80.1%, for patients with a body mass index of, <25, 25-30 and ≥30. Multivariate analysis confirmed body mass index as an independent prognostic factor. CONCLUSION: Our findings suggest that overweight represents an independent prognostic factor in renal cell carcinoma patients. Further research should address the question of why obese people have a higher incidence of renal cell carcinoma, but at the same time a significantly better prognosis than other patients, particularly in the case of localized disease.

Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients.

BACKGROUND: To evaluate the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC). METHODS: We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months. RESULTS: The CRP-level, stratified to three subgroups (CRP ≤ 4, 4-10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4-10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP ≤4 mg/l, respectively. CONCLUSIONS: A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients.

Epidemiological trends in incidence and mortality of hepatobiliary cancers in Germany.

OBJECTIVE: While marked changes in the frequency of hepatobiliary malignancies, most notably hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), have been observed in different populations, no such data have been reported for Germany. We aimed to provide epidemiological data on recent trends in liver-related mortality, specifically mortality from hepatobiliary malignancies, in Germany. MATERIAL AND METHODS: We used incidence and mortality data to determine changes in the frequency of malignant and non-malignant liver disease in Germany over the past 30 years. RESULTS: While overall liver disease mortality has slightly declined in Germany, deaths from hepatobiliary malignancies have declined in women, but remained constant in men. Among hepatobiliary malignancies, ICC stands out, because mortality has more than tripled both in men and women between 1998 and 2008. This is mirrored by a marked increase in new cases reported to local cancer registries, that is, incidence. Over the same time period, HCC and extrahepatic cholangiocarcinoma (ECC) have remained largely constant while gall bladder cancers (GBC) have declined twofold. The rapid rise in ICC is in line with finding from different regions worldwide, but in contrast to recent data from Denmark and France, two of Germany's direct neighbors. CONCLUSIONS: The incidence of and mortality from ICC are rising markedly in Germany. The risk factors underlying this trend are as yet unclear.

Does male sex influence the prognosis of patients with renal cancer?

BACKGROUND: The aim of this study was to investigate the influence of sex on stage, grade, subtype, and prognosis of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: This study included 1,810 patients treated by surgery for RCC at the University Hospitals of Hannover and Marburg between 1990 and 2005. The median follow-up was 54 months. RESULTS: Of all the patients, 1,167 (64.5%) were men and 643 (35.5%) were women. Men were significantly younger (mean, 61.4 vs. 63.5 years; p < 0.001), and suffered more frequently from advanced tumor stages (45.2 vs. 37.6%; p = 0.002) and higher tumor grades (14.1 vs. 11.1%; p = 0.003). Kaplan Meier curves revealed a significant difference in cancer-specific survival between men and women (5-year survival 64.7 vs. 74.0%; p = 0.002). However, unlike tumor stage, grade, and N/M status, sex could not be retained as a significant independent prognostic marker in multivariate analysis. CONCLUSIONS: RCC in men is characterized by higher tumor stages and more frequent metastasis at diagnosis along with inferior tumor-specific survival. However, as sex failed to qualify as an independent prognostic marker for cancer-specific survival, delayed diagnosis due to insufficient or neglected (routine) medical check-up and/or more aggressive tumor biology could be concurrently causative for the higher incidence of RCC in men.

Obesity is associated with improved survival in patients with organ-confined clear-cell kidney cancer.

OBJECTIVES: Obesity increases the risk of developing renal cell carcinoma (RCC); however, it remains unclear whether obesity is associated with RCC aggressiveness and survival. We assessed whether different body mass index (BMI) levels at the time of surgery had an effect on long-term prognosis of RCC patients. METHODS: We evaluated 1,338 clear-cell RCC patients with complete information about their BMI, who had undergone surgery for renal cell cancer at the University Hospitals in Hannover and Marburg between 1991 and 2005. The mean follow-up was 5.1 years. RESULTS: Underweight, normal weight, pre-obesity, and obesity were diagnosed in 14 (1.0%), 444 (33.2%), 593 (44.3%), and 287 (21.4%) RCC patients, respectively. A lower BMI was significantly associated with higher age, tumor grade, and the rate of metastasis at diagnosis. Overweight patients had a significantly lower risk of cancer-related death; their median 5-year tumor-specific survival rate was 70.9% (pre-obese), 74.0% (obese grad I), and 85.6% (obese grad ≥II) as opposed to 63.8% for patients with a BMI below 25 (p < 0.001). Interestingly, subgroup analysis revealed that the positive association between overweight and survival was found in organ-confined RCC only. CONCLUSION: We identified overweight as an independent prognostic marker of improved cancer specific survival in patients with organ-confined but not advanced RCC. Basic research is required to resolve the dilemma of why, if a higher BMI predisposes to RCC, it concurrently prolongs survival after patients have undergone (partial) nephrectomy.

Urinary collecting system invasion is no independent prognostic factor in renal cell carcinoma.

OBJECTIVES: To assess the specific impact of urinary collecting system (UCS) invasion on the long-term prognosis of patients with renal cell carcinoma (RCC). METHODS: We evaluated 1,678 patients with complete information about UCS invasion of their primary RCC who had undergone renal surgery between 1990 and 2005 in two high volume centers (MH Hannover and Marburg, Germany); the mean follow-up was 5.4 years. RESULTS: Hundred and forty-nine (8.9%) patients demonstrated collecting system invasion. These patients incurred a significant increase in the likelihood of cancer-related death (HR 1.7, 95% CI: 1.4-2.0; P < 0.001), their median 5-year tumor-specific survival rate was 45% as opposed to 73% for patients without UCS invasion (P < 0.001). UCS invasion was significantly associated with tumor stage, grade, lymph node, and visceral metastasis at diagnosis but not with age, gender, histologic subtype, or body mass index. However, using multivariate analysis, UCS invasion disqualified as individual prognostic factor for RCC, neither for localized nor for advanced disease. CONCLUSION: Facing the results of this large trial, we do not support the inclusion of UCS invasion into upcoming TNM staging systems. In contrast, future research should focus on novel molecular markers expressed by the tumor and/or specific immunological characteristics of patients with RCC which could improve prediction of RCC-associated prognosis.

Definitive conformal radiotherapy for localized high-risk prostate cancer: a long-term follow-up study with PSA course.

BACKGROUND: The present study investigated the long-term outcome of patients with localized high-risk prostate cancer after definitive conformal radiotherapy. PATIENTS AND METHODS: Ninety-one consecutive patients with stage T1-T4 prostatic carcinoma were treated from 1996 through 2000. Each patient had at least one of the following risk factors: stage > T2b (UICC 1997; 55 patients), Gleason score > 7 (24 patients), or pre-treatment PSA > 20 ng/mL (40 patients). All patients received a conformal radiotherapy of the prostate (median dose, 70 Gy), eighty-three patients (91%) combined with temporary androgen deprivation (median duration, 4 months). All patients were followed continuously during a median of 5.2 years (range, 0.9 to 8.8 years). Biochemical failure after irradiation was defined as a PSA greater than 0.4 ng/mL and three consecutive serum PSA elevations. RESULTS: The 5- and 7-year overall survival rates were 86% and 74%, respectively. The 5- and 7-year biochemical disease-free survival (bDFS) rates were 78% and 66% respectively. The most important predictors of bDFS were Gleason score and central axis dose of 70 Gy or higher. PSA nadir (median, 0.1 ng/mL) was not predictive of subsequent biochemical disease-free survival. CONCLUSION: Our study confirms the findings of others and encourages us to proceed with this treatment policy for T1-T4 high-risk prostate cancer modified by using higher doses and long-term androgen deprivation.

Impact of Time Factors on Outcome in Patients with Head and Neck Cancer Treated with Definitive Radio(Chemo)Therapy.

AIM: To evaluate treatment-related factors such as overall treatment time (OTT) and radiation treatment time (RTT) in head-and-neck cancer. PATIENTS AND METHODS: A total of 216 patients with locoregionally advanced inoperable head and neck cancer were treated with definitive radio(chemo)therapy. Mean follow-up was 37 months. RESULTS: Median time from diagnosis to start of radiotherapy (total waiting time) was 34 days, and comprised of referral waiting time and time for preparatory work. Median RTT was 40 days, and median OTT was 91 days. At 6, 12 and 24 months local recurrence-free survival (LRFS) was 75%, 65% and 60%; metastasis-free survival (MFS) was 84%, 77% and 70%; overall survival (OS) was 72%, 58% and 40%. Tumor stage, boost and chemotherapy were significant for OS, waiting time for preparatory work and RTT were significant for MFS, and referral waiting time and total radiotherapy dose for LRFS. CONCLUSION: RTT ≤40 days was a prognostic factor for better MFS. Prolonged waiting time had a converse effect for radiotherapy with better outcome on MFS and LRFS.

Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?

Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63 % versus 72.2 and 61.9 %; p = 0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6 % versus 80.1 and 75.7 %; p = 0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p = 0.99 and p = 0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted.

The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma.

The prognostic value of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma (chRCC) because this subtype frequently displays nuclear and nucleolar pleomorphism. The present study reevaluates this grading system in a series of patients with nonsarcomatoid chRCC. We identified 176 patients (3.6%) with nonsarcomatoid chRCC in a total of 4897 patients who underwent surgery for renal cell carcinoma at 5 centers in Germany between 1990 and 2010. The mean follow-up was 51.1 months. The 3 groups (G1 versus G2 versus G3/4) were comparable in terms of age, sex, tumor diameter, and lymph node metastasis. They only differed significantly in tumor stage (P = .01) and the incidence of synchronous visceral metastasis (P = .04). The 5-year cancer-specific survival rates were 84.4% for G1 (n = 32), 84.3% for G2 (n = 108), and 74.1% for G3/4 tumors (n = 33) (P = .58). Accordingly, multivariate analysis including age, sex, tumor stage, and metastatic disease did not identify Fuhrman grading as an independent predictor of cancer-specific survival in patients with chRCC (P = .4). We were able to demonstrate in a large multicenter cohort that the Fuhrman grading system does not qualify as a prognostic tool in patients with chRCC.

Small renal cell carcinomas--how dangerous are they really? Results of a large multicenter study.

AIM OF THE STUDY: Modern diagnostic ultrasound and cross-sectional imaging has enabled the detection of increasing numbers of renal tumours. The aim of this study was to investigate the tumour- and patient-specific characteristics and prognosis of small renal cell carcinomas (RCCs) after surgical resection. METHODS: The study included 2197 patients who underwent surgical resection of histologically confirmed RCC ⩽ 4 cm between 1990 and 2011. Median (mean) follow-up was 56.2 (65.5) months. RESULTS: At the time of surgery, tumours were staged as pT ⩾ 3a in 175 (8.0%) cases, 134 (6.2%) were poorly differentiated and 75 (3.5%) were metastasised. The larger the tumour size, the higher was the risk of presenting with stage pT ⩾ 3a (p<0.001), poor tumour differentiation (p = 0.004), microscopic vascular involvement (p = 0.001) and collecting system invasion (p = 0.03). The 5-year cancer-specific survival (CSS) rate was 93.8% for stage pT1a versus 79.4% for stage pT ⩾ 3a (p<0.001), and it was 93.7% for G1-2 versus 76.8% for G3-4 differentiation (p<0.001). Multivariate analysis identified age in years (hazard ratio (HR) 1.04, p<0.001), metastatic disease (HR 12.5, p < 0.001), tumour differentiation (HR 2.8, p<0.001) and non-clear cell histology (HR 0.51, p = 0.02) as independent prognosticators for CSS in patients with small RCC. Interestingly, the 5-year cancer-specific mortality rate for pT1a N/M0 patients was 5.8%. CONCLUSIONS: This large multicenter study has clearly shown that, though most small RCC have a low pathological stage and a good prognosis, there is also a small but significant subgroup of these tumours that are already locally advanced or poorly differentiated.

Clinical behavior of chromophobe renal cell carcinoma is less aggressive than that of clear cell renal cell carcinoma, independent of Fuhrman grade or tumor size.

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC, after clear cell (ccRCC) and papillary RCC. Its lower incidence and frequent exclusion from clinical trials might be why chRCC characteristics have not been extensively studied. The aim of our study was to examine tumor characteristics and long-term prognosis of chRCC compared to ccRCC. We collected 4,210 evaluable patients subjected to surgery for chRCC (n = 176) or ccRCC (n = 4,034) at five centers in Germany (University Hospitals of Hannover, Homburg/Saar, Mainz, Ulm, and Marburg) between 1990 and 2010. Patients with chRCC were significantly younger (mean, 60.1 vs. 62.1 years) and tended to be more frequently female (43.8 vs. 36.5 %). Although Fuhrman grade and median tumor diameter were not significantly different, significantly fewer patients with chRCC than with ccRCC presented with high tumor stage or metastasis at diagnosis (18.5 vs. 43.8 %). Moreover, significantly more chRCC patients were treated with partial nephrectomy (41.5 vs. 26.2 %). Accordingly, 5-year cancer-specific survival (CSS) rates were 83.2 % for chRCC against 75.8 % for ccRCC patients (p = 0.014, log rank). However, in multivariate analysis, chromophobe subtype was not confirmed as a significant positive prognostic factor for RCC (HR 0.88, 95 % CI 0.63-1.24; p = 0.48 Cox regression). This is one of the largest studies to date showing that chRCC is associated with a significantly lower risk of locally invasive tumor growth and metastatic disease than ccRCC. We conclude that the clinical behavior of chRCC is less aggressive than that of ccRCC, independent of Fuhrman grade or tumor size.

Incidence of synchronous and metachronous adrenal metastases following tumor nephrectomy in renal cell cancer patients: a retrospective bi-center analysis.

INTRODUCTION: Synchronous adrenalectomy has become dispensable since retrospective studies have demonstrated no survival benefit when preoperative imaging was normal. The aim of this large bi-institutional study was to determine the appearance of synchronous and metachronous metastases to the adrenal gland as detected by computed tomography and positron emission tomography or magnetic resonance imaging with consecutive surgical removal of suspicious lesions. MATERIALS AND METHODS: We retrospectively reviewed the clinico-pathological records of 2720 patients from two urological centers who underwent radical or partial nephrectomy due to kidney cancer disease. Synchronous adrenalectomy was carried out in 548 of all cases (20.2%). Metachronous adrenalectomy was performed in 24 cases due to suspicious imaging in follow-up. RESULTS: Metastatic spread in patients with synchronous adrenalectomy was found in 29/548 cases (5.3%), as suspected. In metachronous procedures positive pathological results were found in 24 of 24 cases. Among them 54% of all tumor recurrences were detected in the contralateral adrenal gland. CONCLUSIONS: In case of preoperative suspicious imaging an intraoperative frozen section should be performed. Radiological investigations are of high diagnostic value for detecting metachronous tumor growth into the adrenal gland. Surgery in this scenario should be recommended due to the high malignancy rate reported here.

Serum C-reactive protein: a prognostic factor in metastatic urothelial cancer of the bladder.

Until today, there is no reliable prognostic or predictive parameter for the prognosis of patients with metastatic urothelial cancer of the bladder prior to chemotherapy. Recently, serum C-reactive protein (CRP) level has been shown to be associated with survival of patients with various malignancies including localized and metastatic renal cell carcinoma, upper urinary tract as well as penile cancer. The aim of this study was to evaluate the prognostic impact of the pretreatment CRP serum level in patients with metastatic urothelial cancer of the bladder. We retrospectively evaluated 34 patients with metastatic urothelial cancer of the bladder and information about the CRP level prior to chemotherapy. The CRP level was correlated with patient- and tumor-specific characteristics. Kaplan-Meier and log-rank analyses were employed to calculate progression-free (PFS) and overall survival (OS). Receiver operating characteristics (ROC) analysis was used to determine an optimal prognostic CRP cutoff value to predict cancer-specific death. The median PFS to first-line chemotherapy and the OS for the whole cohort were 3.3 and 24.3 months, respectively. Serum CRP in mg/l was significantly associated with patients' survival (HR 1.02, p < 0.001, univariate Cox-regression). ROC analysis identified a CRP value of 80 mg/l to be the optimal cutoff. The median PFS was 4.5 and 3.0 months (p = 0.08; Mann-Whitney test), and the calculated 1-year OS was 82.6 and 22.2 % for patients with a CRP <80 and ≥80 mg/l, respectively (log-rank, p < 0.001). In contrast, neither T-stage, tumor grade, sex, age nor the body mass index was related to the CRP level or associated with overall survival. This is the first analysis revealing that the CRP value prior to systemic treatment might be of prognostic significance and could enable better risk stratification for patients with metastatic urothelial cancer of the bladder.