Maxine Sun

Updated Nomogram Predicting Lymph Node Invasion in Patients with Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection: The Essential Importance of Percentage of Positive Cores

BACKGROUND Few predictive models aimed at predicting the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) are available to date. OBJECTIVE Update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS The study included 588 patients with clinically localised PCa treated between September 2006 and October 2010 at a single tertiary referral centre. INTERVENTION All patients underwent RP and ePLND invariably including removal of obturator, external iliac, and hypogastric nodes. MEASUREMENTS Prostate-specific antigen, clinical stage, and primary and secondary biopsy Gleason grade as well as percentage of positive cores were included in univariable (UVA) and multivariable (MVA) logistic regression models predicting LNI and formed the basis for the regression coefficient-based nomogram. The area under the curve (AUC) method was used to quantify the predictive accuracy (PA) of the model. RESULTS AND LIMITATIONS The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p<0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p≤0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively. The relatively low number of patients included as well as the lack of an external validation represent the main limitations of our study. CONCLUSIONS We report the first update of a nomogram predicting the presence of LNI in patients treated with ePLND. The nomogram maintained high accuracy, even in more contemporary patients (87.6%). Because percentage of positive cores represents the foremost predictor of LNI, its inclusion should be mandatory in any LNI prediction model. Based on our model, those patients with a LNI risk<5% might be safely spared ePLND.

Perioperative Outcomes of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy: Results From the Nationwide Inpatient Sample

BACKGROUND Prior to the introduction and dissemination of robot-assisted radical prostatectomy (RARP), population-based studies comparing open radical prostatectomy (ORP) and minimally invasive radical prostatectomy (MIRP) found no clinically significant difference in perioperative complication rates. OBJECTIVE Assess the rate of RARP utilization and reexamine the difference in perioperative complication rates between RARP and ORP in light of RARPs supplanting laparoscopic radical prostatectomy (LRP) as the most common MIRP technique. DESIGN, SETTING, AND PARTICIPANTS As of October 2008, a robot-assisted modifier was introduced to denote robot-assisted procedures. Relying on the Nationwide Inpatient Sample between October 2008 and December 2009, patients treated with radical prostatectomy (RP) were identified. The robot-assisted modifier (17.4x) was used to identify RARP (n=11 889). Patients with the minimally invasive modifier code (54.21) without the robot-assisted modifier were classified as having undergone LRP and were removed from further analyses. The remainder were classified as ORP patients (n=7389). INTERVENTION All patients underwent RARP or ORP. MEASUREMENTS We compared the rates of blood transfusions, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Multivariable logistic regression analyses of propensity score-matched populations, fitted with general estimation equations for clustering among hospitals, further adjusted for confounding factors. RESULTS AND LIMITATIONS Of 19 462 RPs, 61.1% were RARPs, 38.0% were ORPs, and 0.9% were LRPs. In multivariable analyses of propensity score-matched populations, patients undergoing RARP were less likely to receive a blood transfusion (odds ratio [OR]: 0.34; 95% confidence interval [CI], 0.28-0.40), to experience an intraoperative complication (OR: 0.47; 95% CI, 0.31-0.71) or a postoperative complication (OR: 0.86; 95% CI, 0.77-0.96), and to experience a pLOS (OR: 0.28; 95% CI, 0.26-0.30). Limitations of this study include lack of adjustment for tumor characteristics, surgeon volume, learning curve effect, and longitudinal follow-up. CONCLUSIONS RARP has supplanted ORP as the most common surgical approach for RP. Moreover, we demonstrate superior adjusted perioperative outcomes after RARP in virtually all examined outcomes.

Age-Adjusted Incidence, Mortality, and Survival Rates of Stage-Specific Renal Cell Carcinoma in North America: A Trend Analysis

BACKGROUND The rising incidence of renal cell carcinoma (RCC) has been largely attributed to the increasing use of imaging procedures. OBJECTIVE Our aim was to examine stage-specific incidence, mortality, and survival trends of RCC in North America. DESIGN, SETTING, AND PARTICIPANTS We computed age-adjusted incidence, survival, and mortality rates using the Surveillance Epidemiology and End Results database. Between 1988 and 2006, 43,807 patients with histologically confirmed RCC were included. MEASUREMENTS We calculated incidence, mortality, and 5-yr survival rates by year. Reported findings were stratified according to disease stage. RESULTS AND LIMITATIONS Age-adjusted incidence rate of RCC rose from 7.6 per 100,000 person-years in 1988 to 11.7 in 2006 (estimated annual percentage change [EAPC]: +2.39%; p<0.001). Stage-specific age-adjusted incidence rates increased for localized stage: 3.8 in 1988 to 8.2 in 2006 (EAPC: +4.29%; p<0.001) and decreased during the same period for distant stage: 2.1 to 1.6 (EAPC: -0.57%; p=0.01). Stage-specific survival rates improved over time for localized stage but remained stable for regional and distant stages. Mortality rates varied significantly over the study period among localized stage, 1.3 in 1988 to 2.4 in 2006 (EAPC: +3.16%; p<0.001), and distant stage, 1.8 in 1988 to 1.6 in 2006 (EAPC: -0.53%; p=0.045). Better detailed staging information represents a main limitation of the study. CONCLUSIONS The incidence rates of localized RCC increased rapidly, whereas those of distant RCC declined. Mortality rates significantly increased for localized stage and decreased for distant stage. Innovation in diagnosis and management of RCC remains necessary.

Prognostic Factors and Predictive Models in Renal Cell Carcinoma: A Contemporary Review

CONTEXT The natural history of renal cell carcinoma (RCC) is highly unpredictable. Small renal masses may be accompanied by metastatic disease. Conversely, patients with locally advanced disease may enjoy long-term disease-free survival. OBJECTIVE To review the status of prognostic factors in RCC. EVIDENCE ACQUISITION A literature review was performed using the PubMed, MEDLINE, and Cochrane databases for articles published as of February 15, 2010. Electronic articles published ahead of print were also considered. Search was limited to the English language. Search was conducted using the following keywords: renal cell carcinoma, molecular, tissue, markers, blood, urine, progression, prognosis, risk factor, and survival. Studies were selected according to the relevance of the study, the number of patients included, originality, actuality, and clinical applicability of the results. EVIDENCE SYNTHESIS Four areas of prediction were examined: (1) new RCC diagnostics, (2) RCC grade and stage at diagnosis, (3) disease progression, and (4) disease-specific mortality. All identified reports represented either case series or controlled studies. Although a large number of markers were identified, only a few were validated. Several prognostic factors were integrated in predictive or prognostic models. CONCLUSIONS Several prognostic factors can help discriminate between favourable and unfavourable RCC phenotypes. Of those, several clinical, pathologic, and biologic markers have been tested and validated, and they are used in predictive and prognostic models. Nonetheless, the search continues, especially for informative markers predicting the response to targeted therapies.

Distribution of metastatic sites in renal cell carcinoma: a population-based analysis

BACKGROUND We assessed the distribution of site-specific metastases in patients with renal cell carcinoma (RCC) according to age. Moreover, we evaluated recommendations proposed by guidelines and focused specifically on bone and brain metastases. PATIENTS AND METHODS Patients with metastatic RCC (mRCC) were abstracted from the Nationwide Inpatient Sample (1998-2007). Age was stratified into four groups: <55, 55-64, 65-74 and ≥ 75 years. Cochran-Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of multiple metastatic sites. Finally, we examined the rates of brain or bone metastases according to the presence of other metastatic sites. RESULTS In 11,157 mRCC patients, the rate of multiple metastatic sites decreased with increasing age (P < 0.001). This phenomenon was confirmed in patients with lung, bone, liver and brain metastases (all P ≤ 0.01). The rate of bone metastases was 10% in patients with exclusive abdominal metastases and 49% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 2% in patients with exclusive abdominal metastases and 16% in patients with thoracic and bone metastases. CONCLUSIONS The proportion of patients with multiple metastatic sites is higher in young patients. The rates of bone (10%-49%) and brain (2%-16%) metastases are nonnegligible in mRCC patients.

A Competing-Risks Analysis of Survival After Alternative Treatment Modalities for Prostate Cancer Patients: 1988–2006

BACKGROUND The efficacy of prostate cancer (PCa) treatment modalities is a subject of continuous debate. OBJECTIVE We tested the hypothesis that significant differences in survival rates may exist among PCa patients treated with radical prostatectomy (RP), radiation therapy (RT), and observation. DESIGN, SETTING, AND PARTICIPANTS We focused on 404,604 patients with clinically localized PCa within 17 Surveillance, Epidemiology and End Results registries. MEASUREMENTS Competing-risks survival analyses were used to estimate cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. Patients were stratified according to treatment type, age group, and PCa risk group (high risk: T2c and/or Gleason score 8-10; low to intermediate risk: all others). RESULTS AND LIMITATIONS The 10-yr CSM and OCM rates were 6.1% and 29.2%, respectively. In RP, RT, and observation patients, CSM rates were 3.6%, 6.5%, and 10.8% (p<0.001), respectively; OCM rates were 17.1%, 32.4%, and 48.9% (p<0.001), respectively. In low- to intermediate-risk patients, the lowest CSM (1.3-3.7%) and OCM (6.9-31.6%) rates within all age categories except octogenarians (8.9% and 62.8%, respectively) were recorded in RP. In high-risk patients, the lowest CSM (5.8-7.2%) and OCM (8.7-16.1%) rates in patients aged ≤69 yr were also recorded in RP. RT was equally favorable to RP in the 70-79 age category and appeared ideal in all octogenarian patients. CONCLUSIONS Our results showed that RP provides the most favorable survival rates in most patients. The exception is octogenarian men, in whom RT provides the best results. Finally, the least-favorable outcomes were recorded after observation. However, these findings must be interpreted within the context of the limitations of observational data.

Impact of Adjuvant Radiotherapy on Survival of Patients With Node-Positive Prostate Cancer

PURPOSE The role of adjuvant radiotherapy (aRT) in treating patients with pN1 prostate cancer is controversial. We tested the hypothesis that the impact of aRT on cancer-specific mortality (CSM) in these individuals is related to tumor characteristics. METHODS We evaluated 1,107 patients with pN1 prostate cancer treated with radical prostatectomy and anatomically extended pelvic lymph node dissection between 1988 and 2010 at two tertiary care centers. All patients received adjuvant hormonal therapy with or without aRT. Regression tree analysis stratified patients into risk groups on the basis of their tumor characteristics and the corresponding CSM rate. Cox regression analysis tested the relationship between aRT and CSM rate, as well as overall mortality (OM) rate in each risk group separately. RESULTS Overall, 35% of patients received aRT. At multivariable analysis, aRT was associated with more favorable CSM rate (hazard ratio [HR], 0.37; P < .001). However, when patients were stratified into risk groups, only two groups of men benefited from aRT: (1) patients with positive lymph node (PLN) count ≤ 2, Gleason score 7 to 10, pT3b/pT4 stage, or positive surgical margins (HR, 0.30; P = .002); and (2) patients with PLN count of 3 to 4 (HR, 0.21; P = .02), regardless of other tumor characteristics. These results were confirmed when OM was examined as an end point. CONCLUSION The beneficial impact of aRT on survival in patients with pN1 prostate cancer is highly influenced by tumor characteristics. Men with low-volume nodal disease (≤ two PLNs) in the presence of intermediate- to high-grade, non-specimen-confined disease and those with intermediate-volume nodal disease (three to four PLNs) represent the ideal candidates for aRT after surgery.

Early Salvage Radiation Therapy Does Not Compromise Cancer Control in Patients with pT3N0 Prostate Cancer After Radical Prostatectomy: Results of a Match-controlled Multi-institutional Analysis

BACKGROUND Previous randomised trials demonstrated that adjuvant radiation therapy (aRT) improves cancer control in patients with pT3 prostate cancer (PCa). However, there is currently no evidence supporting early salvage radiation therapy (eSRT) as equivalent to aRT in improving freedom from biochemical recurrence (BCR) after radical prostatectomy (RP). OBJECTIVE To evaluate BCR-free survival for aRT versus observation followed by eSRT in cases of relapse in patients undergoing RP for pT3pN0, R0-R1 PCa. DESIGN, SETTING, AND PARTICIPANTS Using a European multi-institutional cohort, 890 men with pT3pN0, R0-R1 PCa were identified. INTERVENTION All patients underwent RP. Subsequently, patients were stratified into two groups: aRT versus initial observation followed by eSRT in cases of relapse. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Propensity-matched analysis was employed, and patients were stratified into two groups: aRT versus observation and eventual eSRT, defined as RT given at a postoperative serum prostate-specific antigen (PSA) ≤ 0.5 ng/ml at least 6 mo after RP. BCR, defined as PSA >0.20 ng/ml and rising after administration of RT, was compared between aRT and initial observation followed by eSRT in cases of relapse using Kaplan-Meier and Cox regression methods. RESULTS AND LIMITATIONS Overall, 390 (43.8%) and 500 (56.2%) patients were treated with aRT and initial observation, respectively. Within the latter group, 225 (45.0%) patients experienced BCR and underwent eSRT. In the postpropensity-matched cohort, the 2- and 5-yr BCR-free survival rates were 91.4% and 78.4% in aRT versus 92.8% and 81.8% in patients who underwent initial observation and eSRT in cases of relapse, respectively (p=0.9). No differences in the 2- and 5-yr BCR-free survival rates were found, even when patients were stratified according to pT3 substage and surgical margin status (all p ≥ 0.4). These findings were also confirmed in multivariable analyses (p=0.6). Similar results were achieved when the cut-off to define eSRT was set at 0.3 ng/ml (all p ≥ 0.5). CONCLUSIONS The current study suggests that timely administration of eSRT is comparable to aRT in improving BCR-free survival in the majority of pT3pN0 PCa patients. Therefore, eSRT may not compromise cancer control but significantly reduces overtreatment associated with aRT.

A systematic review of the volume-outcome relationship for radical prostatectomy

CONTEXT Due to the complexity and challenging nature of radical prostatectomy (RP), it is likely that both short- and long-term outcomes strongly depend on the cumulative number of cases performed by the surgeon as well as by the hospital. OBJECTIVE To review systematically the association between hospital and surgeon volume and perioperative, oncologic, and functional outcomes after RP. EVIDENCE ACQUISITION A systematic review of the literature was performed, searching PubMed, Embase, and Scopus databases for original and review articles between January 1, 1995, and December 31, 2011. Inclusion and exclusion criteria comprised RP, hospital and/or surgeon volume reported as a predictor variable, a measurable end point, and a description of multiple hospitals or surgeons. EVIDENCE SYNTHESIS Overall 45 publications fulfilled the inclusion criteria, where most data originated from retrospective institutional or population-based cohorts. Studies generally focused on hospital or surgeon volume separately. Although most of these analyses corroborated the impact of increasing volume with better outcomes, some failed to find any significant effect. Studies also differed with respect to the proposed volume cut-off for improved outcomes, as well as the statistical means of evaluating the volume-outcome relationship. Five studies simultaneously compared hospital and surgeon volume, where results suggest that the importance of either hospital or surgeon volume largely depends on the end point of interest. CONCLUSIONS Undeniable evidence suggests that increasing volume improves outcomes. Although it would seem reasonable to refer RP patients to high-volume centers, such regionalization may not be entirely practical. As such, the implications of such a shift in practice have yet to be fully determined and warrant further exploration.

The European Network for the Study of Adrenal Tumors staging system is prognostically superior to the international union against cancer-staging system: A North American validation

BACKGROUND A reclassification of the International Union Against Cancer (UICC) staging system for adrenocortical carcinoma (ACC) patients has recently been proposed by the European Network for the Study of Adrenal Tumors (ENSAT) to better discriminate between cancer-specific mortality (CSM) risk strata. We formally tested the validity of the modified staging system in a large North American population-based cohort. METHODS Kaplan-Meier survival curves depicted CSM rates in the overall population and after stratification according to the 2004 UICC or the 2008 ENSAT-staging system. Cox regression models addressing CSM tested the prognostic value of respectively the UICC or the ENSAT-staging system. Harrells concordance index quantified the accuracy of the standard versus the modified staging system. RESULTS In the overall population (n=573), the CSM-free survival rates at 1, 3, and 5 years were, respectively, 62.9%, 47.0%, and 38.1%. No statistically significant differences in survival were recorded between 2004 UICC stages II and III patients (p=0.1). Conversely, a statistically significant difference was observed between 2008 ENSAT stage II and stage III patients (p<0.001). The 2008 ENSAT-staging system showed higher accuracy (83.0%) in predicting 3-year CSM rates, relative to the 2004 UICC-staging system (79.5%) (p<0.001). CONCLUSION Our study corroborates the superior accuracy of the ENSAT-staging system for ACC relative to the 2004 UICC-staging system. In consequence, the 2008 ENSAT-staging system may warrant consideration in the next update of staging manuals.