Marco Bandini

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.

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.

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).

Contemporary Trends and Survival Outcomes After Aborted Radical Prostatectomy in Lymph Node Metastatic Prostate Cancer Patients

BACKGROUNDnAborted radical prostatectomy (aRP) in lymph node (LN) metastatic (pN1) prostate cancer (PCa) patients showed worse survival in European patients. Contemporary rates of aRP are unknown in North America.nnnOBJECTIVEnTo examine the rate of aRP and its effect on cancer-specific mortality (CSM) in contemporary North American patients.nnnDESIGN, SETTING, AND PARTICIPANTSnWithin the Surveillance Epidemiology and End Results database (2004-2014), we identified 3719 pN1 PCa patients.nnnINTERVENTIONnRP.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnIncidence proportion and median survival of LN metastatic PCa patients who underwent aRP versus completed RP (cRP). Cumulative incidence plots and competing-risks regression (CRR) models tested CSM and other-cause mortality rates according to aRP versus cRP. The effect of selected variables on CSM rate was graphically depicted using LOESS methodology. All analyses were repeated after propensity score matching.nnnRESULTS AND LIMITATIONSnBetween 2004 and 2014, the rate of aRP decreased from 20.4% to 5.6% (p<0.001). Ten-year CSM rates were significantly higher after aRP (38.9% vs 21.6%) versus cRP (p<0.001). In multivariable CRR models, aRP yielded higher CSM (hazard ratio [HR]: 1.99) than cRP. A higher 5-yr CSM rate was recorded after aRP through the entire range of baseline prostate-specific antigen (PSA) values and in patients with up to nine LN metastases. After propensity score matching, aRP resulted in overall higher CSM (HR: 1.72). Higher CSM was recorded after aRP for PSA values up to 50ng/ml and in patients with up to seven LN metastases. Results were limited by a selection bias that applies to aRP patients.nnnCONCLUSIONSnOf contemporary North American patients, 5% are affected by aRP. It confers a significant survival disadvantage that applies to patients with baseline PSA values up to 50ng/ml and in those with up to seven LN metastases.nnnPATIENT SUMMARYnRadical prostatectomy should not be aborted in pN1 prostate cancer individuals.

Survival after Cytoreductive Nephrectomy in Metastatic Non-clear Cell Renal Cell Carcinoma Patients: A Population-based Study

BACKGROUNDnThe benefit of cytoreductive nephrectomy (CNT) for cancer-specific mortality (CSM)-free survival is unclear in contemporary metastatic non-clear cell renal cell carcinoma (non-ccmRCC) patients.nnnOBJECTIVEnTo assess the role of CNT in non-ccmRCC patients.nnnDESIGN, SETTING, AND PARTICIPANTSnWithin Surveillance, Epidemiology, and End Results registry (2001-2014), we identified patients with non-ccmRCC.nnnINTERVENTIONnCNT versus no CNT in non-ccmRCC patients.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnMultivariable logistic regression, cumulative incidence, competing-risks regression models, incremental survival benefit (ISB), conditional survival, and landmark analyses were performed. Sensitivity analyses focused on histological subtypes and most contemporary patients (2010-2014).nnnRESULTS AND LIMITATIONSnOf 851 patients with non-ccmRCC, 67.6% underwent CNT. In multivariable logistic regression, year of diagnosis in contemporary (p<0.001) and intermediate (p=0.008) tertiles, as well as age ≥75 yr (p<0.001) yielded lower CNT rates. Cumulative incidence showed 2-yr CSM of 52.6% versus 77.7%, respectively, after CNT versus no CNT. CSM after CNT versus no CNT was invariably lower in all histologic subtypes and in contemporary patients. Multivariable competing-risks regression models predicting CSM favored CNT (hazard ratio [HR]: 0.38, confidence interval: 0.30-0.47, p<0.001) in all patients and in all subgroups defined by histologic subtypes (HR: 0.14-0.43, all p≤0.02), as well as in contemporary patients (HR: 0.32, p<0.001). The ISB analyses yielded statistically significant and clinically meaningful CSM-free survival benefit of +3 mo after CNT versus no CNT in individuals with observed CSM-free survival ≤24 mo. The 2-yr CSM-free survival increased from baseline of 46.1% versus 19.4% (Δ=26.7%, p<0.001) to 70.3% versus 54.4% (Δ=15.9%, p=0.005) after CNT versus no CNT, in patients that survived 12 mo, respectively. Landmark analyses rejected bias favoring CNT. Data were retrospective.nnnCONCLUSIONSnCSM is lower after CNT for non-ccmRCC in all histologic subtypes and in contemporary patients except for unproven ISB in collecting duct patients. This observation should encourage greater CNT consideration in non-ccmRCC.nnnPATIENT SUMMARYnCytoreductive nephrectomy appears to improve survival in metastatic non-clear cell renal cell carcinoma, but it is used infrequently.

Contemporary rates of adherence to international guidelines for pelvic lymph node dissection in radical cystectomy: a population-based study

ObjectiveTo examine the rates of adherence to guidelines for pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and to identify predictors of omitting PLND.Materials and methodsWe relied on 66,208 patients treated with RC between 2004 and 2013 within the National Inpatients Sample (NIS) database. We examined the rates of PLND according to year of surgery, patient and hospital characteristics. Univariate and multivariate logistic regression analyses assessed the probability of PLND use, after adjusting for year of surgery, age, gender, race, comorbidities, hospital location, teaching status and hospital surgical volume.ResultsOverall, PLND was performed on 54,223 (81.9%) RC patients. The rates PLND at RC significantly increased over the study period from 72.3% in 2004 to 85.9% in 2013, (pu2009<u20090.001). Barriers to PLND at RC consisted of female gender (OR: 1.31; 95% CI 1.25–1.38; pu2009<u20090.001), African American race (OR: 1.21; 95% CI 1.10–1.32; pu2009<u20090.001), intermediate (OR: 1.78; 95% CI 1.68–1.88; pu2009<u20090.001) or low surgical volume institutions (OR: 2.59; 95% CI 2.44–2.74; pu2009<u20090.001), non-teaching institution status (OR: 1.21; 95% CI 1.15–1.27; pu2009<u20090.001) and rural hospital location (OR: 1.13; 95% CI 1.01–1.25; pu2009=u20090.03).ConclusionsIt is encouraging to note increasing rates of PLND at RC over time. Both patients and hospital characteristics influence PLND rates. More efforts should be aimed at reducing inequalities in PLND at RC due to these highly modifiable variables.

Survival benefit of local versus no local treatment for metastatic prostate cancer-Impact of baseline PSA and metastatic substages

To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages.

Tumor characteristics, treatments, and oncological outcomes of prostate cancer in men aged ≤50 years: a population-based study

BackgroundTo examine clinical characteristics, treatment modalities and oncological outcomes of prostate cancer (PCa) according to young (≤50) vs. old age.MethodsOf 407,599 men with primary adenocarcinoma of the prostate within the Surveillance, Epidemiology and End Results (SEER)-database (2004 to 2013), 18,387 were aged ≤50 years (4.5%). Time trends, cumulative incidence, and competing risks regression (CRR) analyses tested for differences between young and old patients. Multi-variable analyses were adjusted for year of diagnosis, race, marital status, Gleason Score, clinical tumor stage, and lymph node status.ResultsYounger men had more favorable tumor characteristics: lower Gleason Score, lower median PSA, and lower rates of metastases at diagnosis compared to their older counterparts. Over time, no local treatment (NLT) rates increased, radical prostatectomy (RP), and brachytherapy (BT) rates decreased and external beam radiation (EBRT) rates remained unchanged. Moreover, the rate of de novo metastatic prostate cancer increased in young patients from 2% (2004) to 3.2% (2013) (pu2009=u20090.004). CRR models showed no difference in prostate cancer-specific mortality (PCSM) between young and old, across all local treatment types.ConclusionsYoung PCa patients have more favorable disease characteristics at presentation, are less frequently treated with RP or BT and more frequently benefit of NLT. PCSM did not differ between young and old patients. However, it is worrisome that recently more young PCa patients are diagnosed at a metastatic stage.

Local treatment for metastatic prostate cancer: A systematic review

The potential oncological benefit for radical treatment in the setting of oligometastatic prostate cancer has been under investigation and is frequently discussed. We carried out a systematic review of English language articles using the Medline database (January 2000 to May 2017) to identify studies reporting local treatment in men with metastatic prostate cancer at diagnosis. Primary end‐points were oncological outcomes, such as cancer‐specific and overall mortality. Secondary end‐points were non‐oncological outcomes, such as complications, operating room time, blood loss or length of hospital stay. Two independent authors reviewed and extracted all search results. Overall, 18 studies reporting on local treatment in metastatic prostate cancer patients were identified (14 original articles, three brief correspondences and one letter to the editor). All of them were retrospective; one partly included prospective data. All studies addressed oncological outcomes, 16 compared local treatment with no‐local treatment and 14 adjusted for confounders using multivariable regression models. All but one study concluded a survival benefit for local treatment in the metastatic setting. Due to heterogeneity of available data, a representative meta‐analysis could not be carried out. Five studies reported non‐oncological outcomes. Although local treatment in metastatic prostate cancer appears to be feasible, its oncological effect remains unclear due to high susceptibility of available studies to significant selection bias.