Firas Abdollah

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.

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.

Pelvic/Retroperitoneal Salvage Lymph Node Dissection for Patients Treated With Radical Prostatectomy With Biochemical Recurrence and Nodal Recurrence Detected by [11C]Choline Positron Emission Tomography/Computed Tomography

BACKGROUND The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. OBJECTIVE To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. DESIGN, SETTING, AND PARTICIPANTS Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. INTERVENTION Patients underwent salvage lymph node dissection (LND). MEASUREMENTS Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. RESULTS AND LIMITATIONS Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p=0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p=0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR=2.92; p=0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p=0.02), higher number of positive lymph nodes (HR: 1.04; p=0.006), and complete BR to salvage LND (HR: 0.31; p=0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. CONCLUSIONS Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.

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.

Chronic Kidney Disease After Nephrectomy in Patients with Small Renal Masses: A Retrospective Observational Analysis

CONTEXT Chronic kidney disease (CKD) is a worldwide health threat associated with increased cardiovascular disease and mortality. OBJECTIVE To examine postoperative CKD in patients with small renal masses (SRMs) treated with partial nephrectomy (PN) or radical nephrectomy (RN). DESIGN, SETTING, AND PARTICIPANTS A US National Cancer Institute Surveillance Epidemiology and End Results (SEER)-Medicare-linked retrospective cohort of 4633 T1aN0M0 renal cell carcinoma (RCC) patients who underwent PN or RN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome of interest was the onset of CKD stage ≥3. Secondary end points comprised acute renal failure (ARF), chronic renal insufficiency (CRI), anemia in CKD, and end-stage renal disease (ESRD). Kaplan-Meier and Cox regression analyses were performed. RESULTS AND LIMITATIONS Postpropensity matching resulted in 840 RN and PN patients. In multivariable analyses, RN patients were 1.9-, 1.4-, 1.8-, and 1.8-fold more likely to have an occurrence of CKD, ARF, CRI, and anemia in CKD, respectively (all p ≤ 0.004). The risk of ESRD between treatment groups failed to achieve statistical significance (p=0.06). CONCLUSIONS PN is associated with more favorable postoperative renal function outcomes relative to RN in the setting of SRMs.

Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy

PURPOSE The optimal timing of postoperative radiotherapy (RT) after radical prostatectomy (RP) is unclear. We hypothesized that a genomic classifier (GC) would provide prognostic and predictive insight into the development of clinical metastases in men receiving post-RP RT and inform decision making. PATIENTS AND METHODS GC scores were calculated from 188 patients with pT3 or margin-positive prostate cancer, who received post-RP RT at Thomas Jefferson University and Mayo Clinic between 1990 and 2009. The primary end point was clinical metastasis. Prognostic accuracy of the models was tested using the concordance index for censored data and decision curve analysis. Cox regression analysis tested the relationship between GC and metastasis. RESULTS The cumulative incidence of metastasis at 5 years after RT was 0%, 9%, and 29% for low, average, and high GC scores, respectively (P = .002). In multivariable analysis, GC and pre-RP prostate-specific antigen were independent predictors of metastasis (both P < .01). Within the low GC score (< 0.4), there were no differences in the cumulative incidence of metastasis comparing patients who received adjuvant or salvage RT (P = .79). However, for patients with higher GC scores (≥ 0.4), cumulative incidence of metastasis at 5 years was 6% for patients treated with adjuvant RT compared with 23% for patients treated with salvage RT (P < .01). CONCLUSION In patients treated with post-RP RT, GC is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low GC scores are best treated with salvage RT, whereas those with high GC scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-RP RT.

Identifying the Best Candidate for Radical Prostatectomy Among Patients with High-Risk Prostate Cancer

BACKGROUND The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial. OBJECTIVE To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. DESIGN, SETTING, AND PARTICIPANTS We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins. INTERVENTION All patients underwent radical retropubic prostatectomy and PLND. MEASUREMENTS Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates. RESULTS AND LIMITATIONS Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p≤0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram. CONCLUSIONS Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.

More Extensive Pelvic Lymph Node Dissection Improves Survival in Patients with Node-positive Prostate Cancer

BACKGROUND The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. OBJECTIVE The relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. DESIGN, SETTING, AND PARTICIPANTS We examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. RESULTS AND LIMITATIONS The average number of RLNs was 20.8 (median: 19; interquartile range: 14-25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p=0.02). Other predictors of CSM were Gleason score 8-10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p ≤ 0.006). The study is limited by its retrospective nature. CONCLUSIONS In PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. PATIENT SUMMARY We found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

A Non–Cancer-Related Survival Benefit Is Associated With Partial Nephrectomy

BACKGROUND Partial nephrectomy (PN) may better protect against other-cause mortality (OCM) when compared with radical nephrectomy (RN) in patients with localized renal cell carcinoma (RCC). OBJECTIVE Test the effect of treatment type on OCM. DESIGN, SETTING, AND PARTICIPANTS Using the Surveillance Epidemiology and End Results-Medicare-linked database, 4956 RN patients (82%) and 1068 PN patients (18%) with T1a RCC were identified (1988-2005). MEASUREMENTS To adjust for inherent differences between treatment types, we relied on propensity-matched analyses. One-to-one matching was performed according to age, sex, race, baseline Charlson comorbidity index (CCI), baseline diagnosis of hypercalcemia and hyperlipidemia, socioeconomic status (SES), population density, tumor size, and year of surgery. The 2- and 5-yr OCM rates were computed using cumulative incidence. Univariable and multivariable competing-risks regression analyses for prediction of OCM were performed according to treatment type. Adjustment was made for cancer-specific mortality (CSM), patient age, CCI, sex, race, SES, tumor grade, and year of surgery. RESULTS AND LIMITATIONS Following propensity-based matching, 1068 RN patients were matched with 1068 PN patients. The 2- and 5-yr OCM rates after nephrectomy were 5.0% and 16.0% for PN versus 6.9% and 18.1% for RN, respectively. In the postpropensity multivariable analyses, patients who underwent PN were significantly less likely to die of OCM compared with their RN-treated counterparts (hazard ratio [HR]: 0.83; 95% confidence interval, 0.69-0.98; p=0.04). Increasing age (HR: 1.08, p<0.001), higher CCI (HR: 1.14, p<0.001), female gender (HR: 0.79, p=0.02), baseline hypercalcemia (HR: 2.05, p=0.03), baseline hyperlipidemia (HR: 0.73, p=0.003), and year of surgery (HR: 0.95, p=0.003) were independent predictors of OCM. CONCLUSIONS Compared with PN-treated patients, RN-treated patients are more likely to die of OCM after surgery, even after adjusting for CSM, as well as baseline CCI. Consequently, PN should be offered whenever technically feasible.