Sebastiano Nazzani

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.

In-hospital length of stay after major surgical oncological procedures

BACKGROUND AND OBJECTIVESnEnhanced recovery after surgery protocols (ERAS) have been developed and implemented as of 2001. However, no previous analyses targeted length of stay (LOS) changes over time after major surgical oncological procedures (MSOPs).nnnMETHODSnBetween 2003 and 2013, we retrospectively identified patients, who underwent prostatectomy, colectomy, cystectomy, mastectomy, gastrectomy, hysterectomy, nephrectomy, oophorectomy, lung resection or pancreatectomy within the Nationwide Inpatient Sample. A total of 3 431 602 assessable patients were identified. We examined temporal trends of LOS after ten MSOPs, as well as LOS determinants and the impact of LOS on total hospital charges (THCGs). Univariable and multivariable linear, log-linear, logistic (MLR) and Poisson regression (MPR) analyses were used.nnnRESULTSnMean and median LOS were respectively 6 and 4 days (IQR 2-7). During the study span, LOS decreased [Estimated annual percentage change (EAPC):xa0-1.89%, pxa0=xa00.0002]. Of the ten examined MSOPs, nine showed a decrease that ranged fromxa0-4.47% in prostatectomy toxa0-0.7% in mastectomy. Conversely, no decrease in LOS was recorded for colectomy (EAPC:+0.37, pxa0=xa00.015). In MPR analyses, robotic [Relative risk (RR):0.68, pxa0=xa00.0003] and laparoscopic (RR: 0.90, pxa0<xa00.0001) surgical approaches were associated with shorter LOS. LOS was directly related to THCGs.nnnCONCLUSIONSnSince the implementation of ERAS protocols, LOS has decreased for nine out of ten MSOPs in a significant fashion. Although these gains may appear marginal on an annual basis, their cumulative effect, over the study span, ranges for 7.7%-49.2%, which can hardly be interpreted as marginal. LOS decrease directly translates in THCGs savings.

Comparison of Partial Versus Radical Nephrectomy Effect on Other-cause Mortality, Cancer-specific Mortality, and 30-day Mortality in Patients Older Than 75 Years

BACKGROUNDnHistorically, partial nephrectomy (PN) showed no benefit on other-cause mortality (OCM) in elderly patients with small renal masses.nnnOBJECTIVEnTo test the effect of PN versus radical nephrectomy (RN) on OCM, cancer-specific mortality (CSM), as well as 30-d mortality in patients with nonmetastatic T1a renal cell carcinoma (RCC), aged ≥75 yr old.nnnDESIGN, SETTING, AND PARTICIPANTSnWithin the Surveillance, Epidemiology and End Results registry (2004-2014), we identified surgically treated patients with nonmetastatic pT1a RCC aged ≥75 yr.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnWe relied on propensity score (PS) matching to reduce the effect of inherent differences between PN and RN. After PS matching, cumulative incidence, multivariable competing-risks regression (CRR) and logistic regression models were used. LOESS plots graphically depicted the relation between nephrectomy type and OCM after adjustment for all the covariates. Landmark analyses at 6 mo tested for immortal time bias.nnnRESULTS AND LIMITATIONSnOf all 4541 patients, 41.6% underwent PN. After 1:1 PS matching, 2826 patients remained. In multivariable CRR models, lower OCM rates were recorded in PN patients (hazard ratio [HR]: 0.67, confidence interval [CI]: 0.54-0.84; p<0.001). LOESS plots showed lower OCM rates after PN across all examined ages. Lower CSM rates were also recorded in PN patients (HR: 0.64, CI=0.44-0.92; p=0.02). Landmark analyses rejected the hypothesis of immortal time bias. Finally, PN did not result in different 30-d mortality rates (odds ratio: 1.87; CI: 0.79-4.47; p=0.2) versus RN. Data are retrospective.nnnCONCLUSIONSnPN results in lower OCM in elderly patients with pT1a RCC. Moreover, PN does not contribute to higher CSM or 30-d mortality in patients aged ≥75 yr. In consequence, PN should be given strong consideration, even in elderly patients.nnnPATIENT SUMMARYnPartial nephrectomy (PN) may protect from renal insufficiency, hypertension, and other unfavorable health outcomes, even in elderly patients. This protective effect results in lower other-cause mortality. Moreover, PN benefits are not undermined by higher cancer-specific mortality or 30-d mortality.

Increasing rate of lymph node invasion in patients with prostate cancer treated with radical prostatectomy and lymph node dissection

OBJECTIVESnTo investigate lymph node invasion (LNI) rates in prostate cancer (PCa) patients. Recent studies demonstrated an inverse stage migration in PCa patients toward more advanced and unfavorable diseases. We hypothesized that this trend is also evident in LNI rates, in PCa patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND).nnnPATIENTS AND METHODSnWithin the Surveillance, Epidemiology, and End Results database (2004-2014), we identified patients who underwent RP and PLND. Annual trends of LNI rates and PLND extent were plotted. Univariable and multivariable logistic regression models tested the hypothesis that LNI rates are increasing annually, even after adjustment for clinical or pathological characteristics.nnnRESULTSnOf 96,874 patients treated with RP and PLND, 4.1% (n = 4,002) exhibited LNI. The rate of LNI (2.5%-6.6%.), the mean (6.5-8.4) and median (5-6) number of removed lymph nodes increased during the study period. In multivariable logistic regression models, more contemporary year of diagnosis was associated with higher LNI rate, when year of diagnosis was modeled as a continuous, categorized or cubic spline variable, with adjustment for either clinical (prostate specific antigen, clinical tumor stage, and biopsy Gleason group) or pathological characteristics (pathologic tumor stage and Gleason group), as well as PLND extent (number of removed lymph nodes).nnnCONCLUSIONnWe confirmed the hypothesis about increasing LNI rate over time in RP patients. This observation implies an increasing rate of unfavorable PCa defined as LNI. This finding is novel for contemporary epidemiological North American or European databases.

A contemporary analysis of radiotherapy effect in surgically treated retroperitoneal sarcoma

BACKGROUND AND PURPOSEnContemporary data regarding the benefit of radiotherapy in surgically treated retroperitoneal sarcoma are scarce. The aim of the study was to evaluate the effect of radiotherapy on cancer specific mortality in surgically treated patients according to tumor size, histological subtype and grade.nnnMATERIAL AND METHODSnWithin Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1226 patients with non-metastatic retroperitoneal sarcoma. Univariable and multivariable logistic regression models tested for predictors of radiotherapy delivery. Univariable and multivariable Cox regression models tested the effect of radiotherapy on cancer specific mortality in the overall population. Subgroup analyses explored the result of tumor grade and tumor size on radiotherapy effect. All analyses were repeated after adjustment according to inverse probability of treatment. Additionally, all analyses were subjected to 1000 bootstrap resamples for internal validation.nnnRESULTSnRadiotherapy was delivered in 372 patients (30.3%). In univariable and multivariable logistic regression models high grade (OR: 1.46, CI:1.12-1.90; pu202f=u202f0.006), and leiomyosarcoma histologic subtype (OR: 2.14, CI: 1.55-2.95; pu202f<u202f0.001) predicted radiotherapy delivery. In the overall population multivariable Cox regression models showed lower cancer specific mortality (HR: 0.73, CI: 0.55-0.96; pu202f=u202f0.025) with radiotherapy. In subgroup analyses multivariable Cox regression models showed radiotherapy benefit predominantly in high grade, large tumor size retroperitoneal sarcomas (HR 0.51: C.I.: 0.30-0.86; pu202f=u202f0.02).nnnCONCLUSIONSnIn this retrospective report, delivery of radiotherapy was associated with lower cancer specific mortality in high grade, large tumor size retroperitoneal sarcoma patients. Our findings are predominantly representative of liposarcomas and leiomyosarcomas that accounted for 90% of study population. Further study is needed to evaluate the role of radiotherapy in retroperitoneal sarcoma patients.

Racial disparities in lymph node dissection at radical prostatectomy: A Surveillance, Epidemiology and End Results database analysis

To test for racial disparities in lymph node dissection rates, lymph node dissection extent, lymph node invasion rates and cancer‐specific mortality in North American African Americans versus non‐Hispanic whites, at radical prostatectomy for clinically localized prostate cancer.

The Impact of Lymph Node Metastases Burden at Radical Prostatectomy

BACKGROUNDnWe hypothesized that a cut-off in positive lymph node (LN) counts may discriminate between cancer-specific mortality (CSM) rates in clinically localized prostate cancer patients treated with radical prostatectomy (RP).nnnOBJECTIVEnTo test this relationship, we relied on different LN count cut-offs, as well as the continuously coded number of positive LNs (NPN).nnnMETHODSnWithin the Surveillance, Epidemiology, and End Results database (2004-2014), we identified patients with DAmico intermediate- or high-risk characteristics who underwent RP and pelvic LN dissection, regardless of pathologic LN stage. Kaplan-Meier analyses and multivariable Cox regression models tested the effect of LN invasion (LNI) on CSM, according to the NPN.nnnRESULTSnOf 30016 patients treated with RP, 6.2% (n=1869) exhibited LNI, with respectively higher rates of LNI in patients with DAmico high- versus intermediate-risk characteristics (11.6% vs 3.4%). Overall, the median age was 63yr, median prostate-specific antigen value was 6.6ng/ml and the median number of removed LNs was six. At 60 mo after RP, CSM rates were, respectively, 6.0% versus 0.8% for patients with and without LNI: multivariable hazard ratio (HR) 4.4 (p<0.001). CSM rates were, respectively, 0.8% for NPN 0, 2.4% for NPN 1-2 (HR: 3.5, p<0.001), and 7.2% for NPN ≥3 (HR: 10.3, p<0.001).nnnCONCLUSIONSnThe NPN is an independent predictor of higher CSM rate. Specifically, patients with one to two positive LNs are at moderately higher risk of CSM than those without LNI, and CSM risk increases sharply in those with ≥3 positive LNs. Our contemporary findings corroborate the NPN cut-offs within previous studies.nnnPATIENT SUMMARYnPatients with three or more positive lymph nodes at radical prostatectomy have significantly higher cancer-specific mortality rates than those without or one to two positive lymph nodes. This stratification can be useful in considering adjuvant treatment options.

Prostate cancer: A valuable tool for prediction of repeat biopsy pathology

Multiparametric MRI (mpMRI) findings are not always accurate in patients with a previous negative prostate biopsy. Truong et al. have developed a nomogram to identify patients with previous negative prostate biopsy who are at elevated risk of harbouring benign histology and should undergo repeat biopsy.

Survival effect of perioperative systemic chemotherapy on overall mortality in locally advanced and/or positive regional lymph node non-metastatic urothelial carcinoma of the upper urinary tract

ObjectivesTo analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma.MethodsWithin the Surveillance, Epidemiology, and End Results database (2004–2014), we identified 1286 patients with T3 or T4, N 0–3xa0M0 UTUC. Kaplan–Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (nu2009=1286), as well as after stratification according to lymph node invasion (LNI).ResultsOverall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, pu2009<xa00.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58–0.87; pu2009=xa00.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48–0.78; pu2009<xa00.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52–1.01; pu2009=xa00.05). All results were confirmed after IPTW adjustment and in landmark analyses.ConclusionsOur results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3–T4, N1–N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.