Raisa S. Pompe

Survival of metastatic renal cell carcinoma patients continues to improve over time, even in targeted therapy era

ObjectiveTo examine the effect of diagnosis year, defined as contemporary (2010–2014), intermediate (2006–2009) and historical (2001–2005) on cancer-specific mortality (CSM) in patients with metastatic renal cell carcinoma (mRCC).MethodsWithin Surveillance, Epidemiology, and End Results registry (2001–2014), we identified patients with mRCC. Cumulative incidence and competing risks regression (CRR) models examined CSM, after accounting for other-cause mortality. Finally, we performed subgroup analyses according to histological subtype: clear-cell mRCC (ccmRCC) versus non-ccmRCC.ResultsWe identified 15,444 patients with mRCC. Of those, 41.0, 28.7 and 30.3% were diagnosed, respectively, in the contemporary, intermediate and historical years. Of all, 47.1, 5.3 and 47.6% were, respectively, ccmRCC, non-ccmRCC and other mRCC histological variants [sarcomatoid mRCC, cyst-associated mRCC, collecting duct carcinoma and mRCC not otherwise specified (NOS)]. Overall, 24-month CSM rates were, respectively, 61.0, 63.7 and 67.3% in contemporary, intermediate and historical patients. In all patients, multivariable CRR models exhibited higher CSM in intermediate (HR 1.11; pxa0<xa00.001) and historical patients (HR 1.24; pxa0<xa00.001) than in contemporary patients. Multivariable CRR models focusing on ccmRCC yielded virtually the same results. However, multivariable CRR models focusing on non-ccmRCC showed no CSM differences according to diagnosis year (all pxa0≥xa00.3).ConclusionThe introduction of new therapeutic agents resulted in CSM-free survival improvement over study time. However, this effect exclusively applies to patients with ccmRCC, but not to those with non-ccmRCC. This observation is in agreement with established efficacy of systemic therapies for ccmRCC, but lesser efficacy of these agents for non-ccmRCC.

Radical prostatectomy or radiotherapy reduce prostate cancer mortality in elderly patients: a population-based propensity score adjusted analysis

PurposeContemporary data regarding the effect of local treatment (LT) vs. non-local treatment (NLT) on cancer-specific mortality (CSM) in elderly men with localized prostate cancer (PCa) are lacking. Hence, we evaluated CSM rates in a large population-based cohort of men with cT1-T2 PCa according to treatment type.MethodsWithin the SEER database (2004–2014), we identified 44,381 men ≥xa075xa0years with cT1-T2 PCa. Radical prostatectomy and radiotherapy patients were matched and the resulting cohort (LT) was subsequently matched with NLT patients. Cumulative incidence and competing risks regression (CRR) tested CSM according to treatment type. Analyses were repeated after Gleason grade group (GGG) stratification: I (3xa0+xa03), II (3xa0+xa04), III (4xa0+xa03), IV (8), and V (9-10).ResultsOverall, 4715 (50.0%) and 4715 (50.0%) men, respectively, underwent NLT and LT. Five and 7-year CSM rates for, respectively, NLT vs. LT patients were 3.0 and 5.4% vs. 1.5 and 2.1% for GGG II, 4.5 and 7.2% vs. 2.5 and 2.8% for GGG III, 7.1 and 10.0% vs. 3.5 and 5.1% for GGG IV, and 20.0 and 26.5% vs. 5.4 and 9.3% for GGG V patients. Separate multivariable CRR also showed higher CSM rates in NLT patients with GGG II [hazard ratio (HR) 3.3], GGG III (HR 2.6), GGG IV (HR 2.4) and GGG V (HR 2.6), but not in GGG I patients (pxa0=xa00.5).ConclusionsDespite advanced age, LT provides clinically meaningful and statistically significant benefit relative to NLT. Such benefit was exclusively applied to GGG II to V but not to GGG I patients.

Short- and Long-term Functional Outcomes and Quality of Life after Radical Prostatectomy: Patient-reported Outcomes from a Tertiary High-volume Center

BACKGROUNDnResults from population-based studies and the Prostate Testing for Cancer and Treatment trial reported worse urinary continence (UC) and erectile function (EF) for radical prostatectomy (RP) patients compared with their radiation or active surveillance counterparts.nnnOBJECTIVEnTo investigate functional outcomes for patients undergoing RP in a high-volume center.nnnDATA, SETTING, AND PARTICIPANTSnA total of 8573 consecutive RP patients (2008-2012) were analyzed.nnnINTERVENTIONnRP.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnStandardized questionnaires assessing EF, UC, and quality of life (QoL), were completed at baseline and annually thereafter. UC was defined as use of 0 or 1 safety pad/d, whereas the regular use of 1 pad/d was considered incontinent. EF was defined as ≥3 points in the International Index of Erectile Function question two. QoL was assessed using the EORTC-QLQ-C30 Global Health/QoL item. Statistics relied on comparison of means and proportions.nnnRESULTS AND LIMITATIONSnEF and UC rates significantly decreased after RP. Overall, 12-mo, 24-mo, and 36-mo EF rates were 45%, 51%, and 53%, but reached up to 65.7% in preoperatively potent patients with bilateral nerve sparing. At 36 mo, 13% reported problems in their partnership. However, at the same time point, 77% were satisfied with their sexual intercourse. UC rates were 89.1%, 91.3%, and 89.0% at 12-mo, 24-mo, and 36-mo postoperatively. Mean EORTC-QLQ-C30 scores ranged from 74 to 79 and remained constant compared to baseline.nnnCONCLUSIONSnAlthough varying definitions hinder direct comparisons to other studies, functional outcomes seemed favorable for patients undergoing RP in a high-volume center and most patients reported excellent QoL.nnnPATIENT SUMMARYnResults of functional outcomes (urinary continence and potency) after radical prostatectomy are better in a high-volume center compared with those obtained from population-based data, and most patients report excellent quality of life after radical prostatectomy.

Improved cancer-specific free survival and overall free survival in contemporary metastatic prostate cancer patients: a population-based study

ObjectivesOver the past decade, several systemic agents as docetaxel, cabazitaxel, sipuleucel-T, abiraterone and enzalutamide have improved overall survival (OS) in metastatic prostate cancer (mPCa) patients. However, to date the OS benefit was not demonstrated in population-based analysis.MethodsBetween 2004 and 2014, 19,047 men with de novo mPCa were identified within the Surveillance Epidemiology and End Results database. Median year of diagnosis resulted in two groups: historical (2004–2008) and contemporary (2009–2014). Due to potentially important differences according to year of diagnosis, we relied on propensity score matching. Propensity-score-matched Kaplan–Meier analyses and Cox regression models (CRMs) tested cancer-specific mortality (CSM) free survival and overall mortality (OM) free survival according to treatment period.ResultsThe propensity-score-matched cohort consisted of 8596 patients with mPCa. Of those, 4298 (50.0%) were historical (2004–2008) and 4298 (50.0%) were contemporary (2009–2014). CSM free survival rates and OM free survival rate were 32 versus 36xa0months (pxa0<xa00.0001) and 26 versus 29xa0months (pxa0<xa00.0001) for, respectively, historical and contemporary patients. In multivariable CRMs, patients diagnosed in contemporary years had lower CSM (HR 0.88; CI 0.82–0.93) and OM (HR 0.88; CI 0.84–0.93) risks compared to historical counterpart (all pxa0<xa00.0001).ConclusionThis population-based study provides the first evidence of improved CSM free survival and OM free survival in patients with de novo mPCa since the introduction of several systemic agents for CRPC patients.

Population‐based validation of the 2014 ISUP Gleason grade groups in patients treated with radical prostatectomy, brachytherapy, external beam radiation or no local treatment

To test discriminant ability of the 2014 ISUP Gleason grade groups (GGG) for prediction of prostate cancer specific mortality (PCSM) after radical prostatectomy (RP), brachytherapy (BT), external beam radiation (EBRT) or no local treatment (NLT) relative to traditional Gleason grading (TGG).

Oncologic and Functional Outcomes after Radical Prostatectomy for High or Very High Risk Prostate Cancer: European Validation of the Current NCCN® Guideline

Purpose: We validated the current NCCN (National Comprehensive Cancer Network®) classification of very high risk patients, and compared the pathological, functional and oncologic outcomes between surgically treated high risk and very high risk patients. Materials and Methods: We retrospectively analyzed 4,041 patients stratified into high risk or very high risk groups who underwent radical prostatectomy between 1992 and 2016. Kaplan‐Meier as well as multivariable logistic and Cox regression analyses were used to compare outcomes between the groups. Results: After radical prostatectomy the rate of adverse pathological features was higher in 1,369 very high risk vs 2,672 high risk cases. Functional outcomes were similar between the groups, with 1‐year continence and potency rates of 81.0% and 43.6% in the very high risk compared to 81.9% and 45.2% in the high risk group, respectively (p = 0.7 and p = 0.9). In a subset of 1,835 patients who underwent radical prostatectomy between 1992 and 2011 (median followup 58.8 months, IQR 36.5–84.6), those with very high risk disease had significantly worse 5 and 8‐year biochemical recurrence‐free survival, metastatic progression‐free survival, prostate cancer specific mortality‐free survival and overall survival rates compared to those with high risk disease. Conclusions: Despite the relatively poor prognosis of patients with high risk prostate cancer, radical prostatectomy results in favorable 5 and 8‐year metastatic progression‐free survival, prostate cancer specific mortality‐free survival and overall survival rates. Relative to high risk cases, their very high risk counterparts have significantly worse pathological and oncologic outcomes, and more frequently require additional therapies. These observations validate the stratification between high risk and very high risk in European patients with prostate cancer. Interestingly, very high risk patients treated with radical prostatectomy did not have a worse functional outcome than their high risk counterparts.

Extent of lymph node dissection improves survival in prostate cancer patients treated with radical prostatectomy without lymph node invasion

To assess the effect of pelvic lymph node dissection (PLND) extent on cancer‐specific mortality (CSM) in prostate cancer (PCa) patients without lymph node invasion (LNI) treated with radical prostatectomy (RP).

Radical prostatectomy neutralizes obesity-driven risk of prostate cancer progression

INTRODUCTIONnObesity negatively affects several prostate cancer (PCa) outcomes, including mortality to PCa. However, the validity of several such associations is still under debate, including its effect on pathological stage at radical prostatectomy (RP) and subsequent biochemical recurrence (BCR), which represents the focus of this study.nnnMETHODSnWe relied on patients with PCa treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable logistic regression analyses tested for association between obesity and non-organ-confined disease (≥pT3 or pN1). Second, multivariable Cox regression analyses examined obesity effect on BCR. Last, in a propensity score-matched cohort, Kaplan-Meier analyses assessed BCR-free survival according to body mass index (kg/m2) (BMI) strata (≥30 vs.<25).nnnRESULTSnOf 16,014 individuals, 2,403 (15%) men were obese (BMI≥30). Median follow-up was 36.4 months (interquartile range: 13.3-60.8). Obese patients were more likely to harbor non-organ-confined disease at final pathology (odds ratio = 1.27; 95% CI: 1.13-1.43; P<0.001) but did not have higher BCR rates (hazard ratio = 0.98; 95% CI: 0.86-1.11; P = 0.7). Similarly, BCR-free survival was not different between obese and nonobese men, after propensity score matching (log rank P = 0.9).nnnCONCLUSIONnObesity (BMI ≥30) might predispose to higher rates of non-organ-confined disease at RP. However, obesity was not an independent predictor of BCR after surgery. Consequently, the unfavorable effect of obesity on PCa might be limited to local spread of the disease and might be neutralized after RP.

North American Population-Based Validation of the National Comprehensive Cancer Network Practice Guideline Recommendation of Pelvic Lymphadenectomy in Contemporary Prostate Cancer

BACKGROUND. National Comprehensive Cancer Network (NCCN) guidelines recommend a pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) if a nomogram predicted risk of lymph node invasion (LNI) is ≥2%. We examined this and other thresholds, including nomogram validation.

Effect of pathological high-risk features on cancer-specific mortality in non-metastatic clear cell renal cell carcinoma: a tool for optimizing patient selection for adjuvant therapy

PurposeAdjuvant therapies for non-metastatic renal cell carcinoma (nmRCC) are being tested to improve outcomes in patients with high-risk (hR) nmRCC. The objective of the current study is to test the ability of three hR features to identify patients who are at the highest risk of cancer-specific mortality (CSM) after partial or radical nephrectomy.MethodsWithin the Surveillance Epidemiology and End Results (SEER) database (1988–2013), we identified 23,632xa0nm “clear cell” RCC partial or radical nephrectomy patients with hR features: Fuhrman grade (FG) 3 or 4 or pathological classifications T3a or T3b or lymph node invasion (LNI), or combination of these. Kaplan–Meier analyses (KM) and multivariable Cox’s regression models (CRM) evaluated the effect of hR features on CSM.ResultsOverall 11,568 (48.9%) patients harbored FG3-4, 5575 (23.6%) pT3a/b, 140 (0.6%) LNI, 5366 (22.7%) FG3-4 and pT3a/b, 183 (0.8%) LNI and pT3a/b, 203 (0.9%) LNI and FG3-4 and 597 (2.5%) LNI, FG3-4 and pT3a/b. Median CSM-free survival was 51, 58 and 22xa0months for LNI and pT3a/b, for LNI and FG3-4 and for LNI, FG3-4 and pT3a/b and was not reached for the other groups. These results remained unchanged in multivariable CRMs, where all hR features represented independent predictors.ConclusionsIndividuals with combination of LNI with FG3-4 or pT3a/b and patients with all three hR features are at highest risk of CSM. In consequence, these patients may represent ideal candidates for adjuvant therapy either in clinical practice or future prospective trials.