Philipp Mandel

Impact of Histologic Subtype on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus

BACKGROUND Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

External Validation of the CAPRA-S Score to Predict Biochemical Recurrence, Metastasis and Mortality after Radical Prostatectomy in a European Cohort

PURPOSE The CAPRA-S score predicts prostate cancer recurrence based on pathological information from radical prostatectomy. To our knowledge CAPRA-S has never been externally validated in a European cohort. We independently validated CAPRA-S in a single institution European database. MATERIALS AND METHODS The study cohort comprised 14,532 patients treated with radical prostatectomy between January 1992 and August 2012. Prediction of biochemical recurrence, metastasis and cancer specific mortality by CAPRA-S was assessed by Kaplan-Meier analysis and the c-index. CAPRA-S performance to predict biochemical recurrence was evaluated by calibration plot and decision curve analysis. RESULTS Median followup was 50.8 months (IQR 25.0-96.0). Biochemical recurrence developed in 20.3% of men at a median of 21.2 months (IQR 7.7-44.9). When stratifying patients by CAPRA-S risk group, estimated 5-year biochemical recurrence-free survival was 91.4%, 70.4% and 29.3% in the low, intermediate and high risk groups, respectively. The CAPRA-S c-index to predict biochemical recurrence, metastasis and cancer specific mortality was 0.80, 0.85 and 0.88, respectively. Metastasis developed in 417 men and 196 men died of prostate cancer. CONCLUSIONS The CAPRA-S score was accurate when applied in a European study cohort. It predicted biochemical recurrence, metastasis and cancer specific mortality after radical prostatectomy with a c-index of greater than 0.80. The score can be valuable in regard to decision making for adjuvant therapy.

Nerve-sparing Surgery Technique, Not the Preservation of the Neurovascular Bundles, Leads to Improved Long-term Continence Rates After Radical Prostatectomy

BACKGROUND The effect of preservation of neurovascular bundles (NVBs) during radical prostatectomy (RP) on continence remains controversial. OBJECTIVE To analyze if the differing surgical techniques of nerve-sparing (NS) versus non-nerve-sparing (NNS) RP and not the preservation of the NVB itself may be responsible for differences in continence rates. DESIGN, SETTING, AND PARTICIPANTS A total of 18 427 men who underwent RP from 2002 to 2014 in a single high-volume center were analyzed retrospectively. Patients with bilateral NS RP, with primary NNS RP, and with bilateral secondary resection of the NVBs for positive frozen-section results after an initial bilateral nerve sparing (secNNS) RP were studied. INTERVENTION NS, NNS, or secNNS RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable and propensity score matched analyses adjusting for age, prostate volume, and year of surgery were performed to assess differences in continence rates after RP. Continence was defined as the use of no or one safety pad per day. RESULTS AND LIMITATIONS Post-RP urinary continence rates at 1 wk, 3 mo, and 12 mo were 59.8%, 76.2%, 85.4% in the NS group, 39.5%, 59.5%, and 87.0% in the secNNS group, and 29.1%, 52.8%, and 70.5% in the NNS group. Continence rates at 12 mo after surgery did not differ significantly between patients who had bilateral NS and patients who had resection of both NVBs after an initial nerve-sparing technique (secNNS). In contrast, when comparing the NNS study groups with initial NNS versus secNNS, the latter group had significantly higher continence rates after 12 mo. CONCLUSIONS Our results indicate that the meticulous apical dissection associated with the NS RP technique rather than the preservation of the NVBs itself may have a positive impact on long-term urinary continence rates. PATIENT SUMMARY We looked at continence rates after nerve-sparing (NS) versus non-NS radical prostatectomy (RP). NS surgery technique but not the preservation of the neurovascular bundles led to improved long-term continence rates after RP.

Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer after Radical Prostatectomy

PURPOSE We analyzed the impact of salvage lymph node dissection on the prognosis in patients with biochemical recurrence and positive lymph nodes on positron emission tomography/computerized tomography after radical prostatectomy. MATERIALS AND METHODS We retrospectively analyzed the records of 58 patients who underwent pelvic and/or retroperitoneal salvage lymph node dissection from June 2005 to February 2012. Biochemical response was defined as prostate specific antigen less than 0.2 ng/ml 40 days after salvage treatment. Biochemical recurrence in those with a biochemical response was defined as prostate specific antigen greater than 0.2 ng/ml and increasing. Kaplan-Meier curves were used to assess time to biochemical recurrence, clinical recurrence and cancer specific survival. Cox and binary logistic regressions were used to determine factors influencing clinical recurrence and biochemical response. RESULTS Median followup after salvage lymph node dissection was 39 months. A total of 13 patients (22.4%) achieved a biochemical response. Only 1 patient remained free of biochemical recurrence during followup. Clinical recurrence developed in 25 patients (48.1%) after salvage treatment. Six patients (10.3%) died of disease, including 4 with indeterminate extralymphatic findings on positron emission tomography/computerized tomography before salvage therapy. The 5-year cancer specific survival rate was 71.1%. Patients with a complete biochemical response showed a trend toward a longer time to clinical recurrence (p = 0.20). Biochemical response did not influence cancer specific survival. CONCLUSIONS Salvage lymph node dissection in patients with biochemical recurrence and positive lymph nodes on positron emission tomography/computerized tomography led to a biochemical response in a certain proportion. Most patients progressed to biochemical recurrence after salvage treatment but almost half showed no further clinical recurrence. Cancer specific mortality occurred predominantly in patients with prior suspicion of extralymphatic lesions. Salvage lymph node dissection may delay androgen deprivation therapy and clinical recurrence in select patients.

High Chance of Late Recovery of Urinary and Erectile Function Beyond 12 Months After Radical Prostatectomy

Urinary incontinence (UI) and erectile dysfunction (ED) after radical prostatectomy (RP) can impose a strong burden. While most studies focus on certain time points after RP when analyzing functional outcome, there is paucity of evidence on late functional recovery in patients with UI or ED at 12 mo after RP. Using longitudinal patient data from a large European single-center, we show that the chance of regaining continence among patients (n=974) with UI (≥1 pad/24h) at 12 mo after RP was 38.6% after 24 mo and 49.7% after 36 mo. The corresponding rates for patients (n=1115) with ED (defined as International Index of Erectile Function-5 score <18) at 12 mo after RP were 30.8% at 24 mo and 36.5% at 36 mo after RP. Patients with postoperative UI or ED 12 mo after RP should be counseled about their good chance of achieving continence or potency in the course of time. PATIENT SUMMARY We analyzed the probability of functional recovery among patients with urinary incontinence (UI) and erectile dysfunction (ED) 12 mo after radical prostatectomy. We found that up to 49.7% (36.5%) of patients with UI (ED) regain function within the next 24 mo and should be informed about these encouraging numbers.

Impact of Synchronous Metastasis Distribution on Cancer Specific Survival in Renal Cell Carcinoma after Radical Nephrectomy with Tumor Thrombectomy

PURPOSE Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Does Cytoreductive Prostatectomy Really Have an Impact on Prognosis in Prostate Cancer Patients with Low-volume Bone Metastasis? Results from a Prospective Case-Control Study

The impact of cytoreductive radical prostatectomy (CRP) on oncological outcomes in patients with prostate cancer (PCa) and distant metastases has been demonstrated by retrospective data with their potential selection bias. Using prospective institutional data, we compared the outcomes between 43 PCa patients with low-volume bone metastases (1-3 lesions) undergoing CRP (median follow-up 32.7 mo) and 40 patients receiving best systemic therapy (BST; median follow-up 82.2 mo). The inclusion criteria for both cohorts were identical. So far, no significant difference in castration resistant-free survival (p=0.92) or overall survival (p=0.25) has been detected. Compared to recent reports, the outcomes for our control group are more favorable, indicating a potential selection bias in the previous retrospective studies. Therefore, the unclear oncological effect has to be weighed against the potential risks of CRP. However, patients benefit from a significant reduction in locoregional complications (7.0% vs 35%; p<0.01) when undergoing CRP. PATIENT SUMMARY In this study we analyzed the impact of surgery in patients with prostate cancer and bone metastases. Using prospective data, we could not show a significant benefit of surgery on survival, but the rate of locoregional complications was lower. Therefore, patients should be treated within prospective trials evaluating the role of cytoreductive prostatectomy in low-volume, bone metastatic prostate cancer.

Adjuvant radiation therapy is associated with better oncological outcome compared with salvage radiation therapy in patients with pN1 prostate cancer treated with radical prostatectomy

To analyse the comparative effectiveness of no treatment (NT) or salvage radiation therapy (sRT) at biochemical recurrence (BCR) vs adjuvant radiation therapy (aRT) in patients with lymph node (LN)‐positive prostate cancer (PCa) after radical prostatectomy (RP).

Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy: Multi-Institutional Analysis

PURPOSE The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.

Extent of lymph node dissection and recurrence-free survival after radical cystectomy: A meta-analysis

INTRODUCTION Lymph node dissection (LND) at the time of radical cystectomy (RC) is the standard of care in the treatment of muscle-invasive bladder cancer. However, no final consensus about its optimal extent has been reached. METHODS We conducted a meta-analysis to determine the effect of the extent of LND on 5-year recurrence-free survival and its complication rates in patients undergoing RC. A systematic search of MEDLINE, PubMed, and EMBASE has been performed. All studies published until June 2013 and providing information on 5-year recurrence-free survival were included in the analysis. RESULTS We analyzed the recurrence-free survival data of 11 studies on standard or extended LND or both in patients undergoing RC. The extended (above the bifurcation of iliac vessels) LND showed a significant trend toward a higher proportion of lymph node-positive patients (odds ratio = 1.39; 95% CI: 0.96-2.00; P = 0.08). Including all studies that compare extended with standard LND, the overall odds ratio for the 5-year recurrence-free survival is 1.63 (95% CI: 1.28-2.07, P<0.001), showing a strong and statistical significant survival benefit for the group of patients who underwent extended LND. Moreover, the weighted average 5-year recurrence-free survival rate of all existing studies on standard LND is significantly different from the ones reporting extended LND rates. No differences in perioperative mortality or complication rates were reported. CONCLUSION The present meta-analysis provides evidence to the positive effect of extended LND on recurrence-free survival and its diagnostic benefit in patients undergoing RC. Patients who underwent extended LND did not suffer from higher complication rates or perioperative mortality.