Contemporary survival in metastatic bladder cancer patients: A population-based study.

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

Survival of stage III non-seminoma testis cancer patients versus simulated controls, according to race/ethnicity.

BACKGROUND: It is unknown whether 5-year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non-seminoma testicular germ cell tumor (NS-TGCT) patients and simulated age-matched male population-based controls, according to race/ethnicity groups. METHODS: We identified newly diagnosed (2004-2014) stage III NS-TGCT patients within the Surveillance Epidemiology and End Results database 2004-2019. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS rates between stage III NS-TGCT patients and simulated age-matched male population-based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer-specific mortality (CSM) and other-cause mortality (OCM) were computed. RESULTS: Of 2054 stage III NS-TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5-year OS difference between stage III NS-TGCT patients versus simulated age-matched male population-based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5-year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5-year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%). CONCLUSION: Relative to SSA Life Tables, the highest 5-year OS disadvantage applied to stage III NS-TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order.

Neoadjuvant Versus Adjuvant Chemotherapy in Non-Metastatic Locally-Advanced Stage Radical Cystectomy Candidates.

INTRODUCTION: Administration of chemotherapy before radical cystectomy (RC) in neoadjuvant setting (NAC) or after RC in adjuvant setting (ADJ) are both associated with a survival benefit relative to RC alone. However, no study directly compared the magnitude of such benefit associated with NAC versus ADJ in locally-advanced UCUB patients (T3-T4N0M0). We addressed this knowledge gap. METHODS: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified T3-T4N0M0 UCUB patients who underwent NAC+RC or RC+ADJ. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied in T3 and then T4 patient subgroups. RESULTS: Of 875 assessable patients, 603 harbored T3 stage (69.0%) and 272 harbored T4 stage (31.0%). Of all 875, 563 (64.0%) underwent RC+ADJ versus 312 (36.0%) NAC+RC. NAC+RC rates increased over time (EAPC=+6.1%, P = .001). Cumulative incidence plots derived five-year CSM rates were 40.3% in NAC+RC versus 36.1% in RC+ADJ patients (P = .2). In multivariable CRR models that also adjusted for OCM, no statistically significant difference in CSM was recorded when NAC+RC was compared to RC+ADJ (HR:0.85, P = .1). Virtually the same observations were made in subgroup analyses where CSM associated with NAC+RC was not different from that recorded in RC+ADJ (HR: 0.89 and P = .4 in T3 stage and HR:0.8 and P = .2 in T4 stage). CONCLUSION: In locally-advanced UCUB, NAC rates have sharply increased over time. However, the approach based on neoadjuvant chemotherapy prior to RC have not resulted in a statistically significant CSM benefit relative to RC+ADJ.

Preoperative Plasma Insulin-Like Growth Factor-I and Its Binding Proteins-Based Risk Stratification of Patients Treated With Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.

Improved Survival in Contemporary Community-Based Patients With Metastatic Clear-Cell Renal Cell Carcinoma Undergoing Active Treatment.

BACKGROUND: We hypothesized that the evolving treatment paradigms recommended based on phase III trials may have translated into improved overall survival (OS) in contemporary community-based patients with clear-cell metastatic renal cell carcinoma (ccmRCC) undergoing active treatment. PATIENTS AND METHODS: Within the SEER database, contemporary (2017-2020) and historical (2010-2016) patients with ccmRCC treated with either systemic therapy (ST), cytoreductive nephrectomy (CN), or both (ST+CN) were identified. Univariable and multivariable Cox-regression models were used. RESULTS: Overall, 993 (32%) contemporary versus 2,106 (68%) historical patients with ccmRCC were identified. Median OS was 41 months in contemporary versus 25 months in historical patients (Δ=16 months; P<.001). In multivariable Cox-regression analyses, contemporary membership was independently associated with lower overall mortality (hazard ratio [HR], 0.7; 95% CI, 0.6-0.8; P<.001). In patients treated with ST alone, median OS was 17 months in contemporary versus 10 months in historical patients (Δ=7 months; P<.001; multivariable HR, 0.7; P=.005). In patients treated with CN alone, median OS was not reached in contemporary versus 33 months in historical patients (Δ=not available; P<.001; multivariable HR, 0.7; P<.001). In patients treated with ST+CN, median OS was 38 months in contemporary versus 26 months in historical patients (Δ=12 months; P<.001; multivariable HR, 0.7; P=.003). CONCLUSIONS: Contemporary community-based patients with ccmRCC receiving active treatment clearly exhibited better survival than their historical counterparts, when examined as one group, as well as when examined as separate subgroups according to treatment type. Treatment advancements of phase III trials seem to be applied appropriately outside of centers of excellence.

Temporal Trends and Cancer-Specific Mortality in Nonmetastatic Muscle-Invasive Urothelial Carcinoma of the Urinary Bladder Treated With Trimodal Therapy.

INTRODUCTION: Trimodal therapy (TMT) is guideline-recommended for the management of organ confined urothelial carcinoma of urinary bladder (UCUB). However, temporal trends in TMT use and cancer-specific mortality free-survival (CSM-FS) between historical TMT versus contemporary TMT have not been assessed. We addressed this knowledge gap. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified nonmetastatic UCUB patients with cT2-T4aN0-N2 treated with TMT, defined as the combination of transurethral resection of bladder tumor, chemotherapy and radiotherapy. Temporal trends described TMT use over time. Subsequently, patients were divided between historical (2004-2012) versus contemporary (2013-2020) cohorts. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM-FS. Separate analyses addressed patients with organ confined (OC: cT2N0M0) versus nonorgan confined (NOC: cT3-4a and/or cN1-2) clinical stages. RESULTS: Of 4,097 assessable UCUB TMT patients, 1744 (43%) were treated in the historical period (2004-2012) versus 2353 (58%) in the contemporary period (2013-2020). TMT use increased over time in OC patients (EAPC:+3.4%, P < .001), as well as in NOC (EAPC:+2.7%, P < .001). In OC stage, median CSM-FS was 55.3% in historical versus 49.0% in contemporary patients (HR:0.75, P < .001). Similarly, in NOC stage, 5-year median CSM-FS was 43.0% in historical versus 32.8% in contemporary patients (HR:0.78, P = .01). CONCLUSION: TMT rates have increased over time in both OC and NOC patients. Contemporary TMT patients benefit of better cancer-specific survival. Interestingly, this benefit applies equally to OC and NOC TMT-treated patients.

Unmarried Status Effect on Stage at Presentation and Treatment Patterns in Non-Metastatic Upper Tract Urothelial Carcinoma Patients.

BACKGROUND: Unmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T3-4N0-2) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion. RESULTS: Of all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T3-4N0-2), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients. CONCLUSIONS: Unmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients.

Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients.

BACKGROUND: It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. METHODS: Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. RESULTS: Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). CONCLUSIONS: In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).

Sarcomatoid Dedifferentiation as a Predictor of Cancer-Specific Mortality in Surgically Treated Localized Renal Cell Carcinoma.

BACKGROUND: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. RESULTS: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. CONCLUSIONS: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.

A Systematic Review and Meta-analysis of the Impact of Local Therapies on Local Event Suppression in Metastatic Hormone-sensitive Prostate Cancer.

CONTEXT: It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression. OBJECTIVE: To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP). EVIDENCE ACQUISITION: Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT). EVIDENCE SYNTHESIS: Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract. CONCLUSIONS: In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting. PATIENT SUMMARY: Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.

The effect of married status on cancer-specific mortality in nonmetastatic pelvic liposarcoma patients according to sex.

BACKGROUND: In nonmetastatic pelvic liposarcoma patients, it is unknown whether married status is associated with better cancer-control outcome defined as cancer-specific mortality (CSM). We addressed this knowledge gap and hypothesized that married status is associated with lower CSM rates in both male and female patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), nonmetastatic pelvic liposarcoma patients were identified. Kaplan-Meier plots and univariable and multivariable Cox regression models (CRMs) predicting CSM according to marital status were used in the overall cohort and in male and female subgroups. RESULTS: Of 1078 liposarcoma patients, 764 (71%) were male and 314 (29%) female. Of 764 male patients, 542 (71%) were married. Conversely, of 314 female patients, 192 (61%) were married. In the overall cohort, 5-year cancer-specific mortality-free survival (CSM-FS) rates were 89% for married versus 83% for unmarried patients (Δ = 6%). In multivariable CRMs, married status did not independently predict lower CSM (hazard ratio [HR]: 0.74, p = 0.06). In males, 5-year CSM-FS rates were 89% for married versus 86% for unmarried patients (Δ = 3%). In multivariable CRMs, married status did not independently predict lower CSM (HR: 0.85, p = 0.4). In females, 5-year CSM-FS rates were 88% for married versus 79% for unmarried patients (Δ = 9%). In multivariable CRMs, married status independently predicted lower CSM (HR: 0.58, p = 0.03). CONCLUSIONS: In nonmetastatic pelvic liposarcoma patients, married status independently predicted lower CSM only in female patients. In consequence, unmarried female patients should ideally require more assistance and more frequent follow-up than their married counterparts.

Use of inpatient palliative care in metastatic urethral cancer.

BACKGROUND: In metastatic urethral cancer, temporal trends, and patterns of inpatient palliative care (IPC) use are unknown. METHODS: Relying on the National Inpatient Sample (2006-2019), metastatic urethral cancer patients were stratified according to IPC use. Estimated annual percentage changes (EAPC) analyses and multivariable logistic regression models (LRM) for the prediction of IPC use were fitted. RESULTS: Of 1,106 metastatic urethral cancer patients, 199 (18%) received IPC. IPC use increased from 5.8 to 28.0% over time in the overall cohort (EAPC +9.8%; P < 0.001), from <12.5 to 35.1% (EAPC +11.2%; P < 0.001), and from <12.5 to 24.7% (EAPC +9.4%; P = 0.01) in respectively females and males. Lowest IPC rates were recorded in the Midwest (13.5%) vs. highest in the South (22.5%). IPC patients were more frequently female (44 vs. 37%), and more frequently exhibited bone metastases (45 vs. 34%). In multivariable LRM, female sex (multivariable odds ratio [OR] 1.46, 95% confidence interval [CI] 1.05-2.02; P = 0.02), and bone metastases (OR 1.46, 95%CI 1.02-2.10; P = 0.04) independently predicted higher IPC rates. Conversely, hospitalization in the Midwest (OR 0.53, 95%CI 0.31-0.91; P = 0.02), and in the Northeast (OR 0.48, 95%CI 0.28-0.82; P = 0.01) were both associated with lower IPC use than hospitalization in the West. CONCLUSION: IPC use in metastatic urethral cancer increased from a marginal rate of 5.8% to as high as 28%. Ideally, differences according to sex, metastatic site, and region should be addressed to improve IPC use rates.

The State of Intermediate Clinical Endpoints as Surrogates for Overall Survival in Prostate Cancer in 2024.

In the past, selection of intermediate clinical endpoints (ICEs) in prostate cancer (PCa) trials largely depended on qualitative assessments; however, the advancing quality of research necessitates a robust correlation with overall survival (OS). This review summarises the results from several high-quality meta-analyses that explored the validity of ICEs as surrogates for OS. We found strong evidence that metastasis-free survival can serve as an ICE in localized PCa. In advanced disease, valid ICEs were identified only within the context of metastatic hormone-sensitive PCa, including radiological and clinical progression-free survival; however, concerns remain regarding their use owing to the limited generalisability of the data used to validate their surrogacy. PATIENT SUMMARY: Intermediate clinical endpoints can reduce the costs of trials and allow earlier introduction of new treatment methods. This article summarises results from studies verifying the validity of these endpoints as surrogates for overall survival.

Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

BACKGROUND: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. METHODS: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). RESULTS: Patients with TT showed lower BMI (24 vs. 26 kg/m2) and preoperative Hb (11 vs. 14 g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). CONCLUSIONS: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

Contemporary validation of cT1a vs. cT1b substaging of incidental prostate cancer.

OBJECTIVE: The cT1a vs. cT1b substratification was introduced in 1992 but never formally tested since. We tested the discriminative ability of cT1a vs. cT1b substaging on cancer-specific survival (CSS) in contemporary incidental prostate cancer (PCa) patients. DESIGN, SETTING AND PARTICIPANTS: Incidental (cT1a/cT1b) PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier estimates, as well as uni- and multivariable Cox regression models predicted CSS at five years. Subgroup analyses addressed CSS at five years according to active vs. no local treatment (NLT) as well as Gleason score sum (GS; 6 vs. 7 vs. ≥ 8). RESULTS AND LIMITATION: We identified a total of 5,155 incidental prostate cancer patients of which 3,035 (59%) were stage cT1a vs. 2,120 (41%) were stage cT1b. In all incidental PCa patients, CSS at five years was 95% (95% CI 0.94-0.96). In cT1a patients, CSS at five years was 98 vs. 90% in cT1b patients (p < 0.001). In multivariable Cox regression analyses, cT1b independently predicted 2.8-fold higher CSM than cT1a (HR 2.5, 95% CI 1.8-3.6, p < 0.001) for incidental PCa patients who underwent NLT. In subgroup analyses, cT1b represented an independent predictor of higher CSM in GS ≥ 8 (HR 3.0, 95% CI 1.4-6.2, p = 0.003), and GS 7 (HR 3.9, 95% CI 1.6-9.7 p = 0.002) patients who underwent NLT. For actively treated patients, cT1b was not independently associated with worse CSM. CONCLUSION: The historical subclassification of cT1a vs. cT1b in incidental PCa patients displayed a strong ability to discriminate CSS in contemporary GS 7 and GS ≥ 8 patients who underwent NLT. However, no statistically significant difference was recorded in actively treated patients. In consequence, the importance of the current substage stratification predominantly applies to GS ≥ 8 patients who undergo a non-active treatment approach.

Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis.

BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

Perioperative complications and in-hospital mortality in radical cystectomy patients with heart-valve replacement.

PURPOSE: To assess in-hospital mortality and complication rates after radical cystectomy (RC) in patients with history of heart-valve replacement. MATERIALS AND METHODS: Using the National Inpatient Sample (2000-2019), non-metastatic bladder cancer patients undergoing RC were stratified according to history of heart-valve replacement. Regression models (RM) predicted hospital outcomes. RESULTS: Of 25,535 RC patients, 250 (1.0%) harbored history of heart-valve replacement. Heart-valve replacement patients were older (median 74 vs. 70 years), more frequently male (87.2 vs. 80.6%), and more frequently had Charlson comorbidity index ≥3 (26.8 vs. 18.9%). In RC patients with history of heart-valve replacement vs. others, 62 vs. 2634 (24.8 vs. 10.4%) experienced cardiac complications, 28 vs. 3092 (11.2 vs. 12.2%) intraoperative complications, 11 vs. 1046 (4.4 vs. 4.1%) infections, <11 vs. 594 (<4.4 vs. 2.3%) perioperative bleeding, <11 vs. 699 (<4.4 vs. 2.8%) vascular complications, 74 vs. 6225 (29.6 vs. 24.7%) received blood transfusions, 37 vs. 3054 (14.8 vs. 12.1%) critical care therapy (CCT), and in-hospital mortality was recorded in <11 vs. 463 (<4.4 vs. 1.8%) patients. In multivariable RM, history of heart-valve replacement independently predicted cardiac complications (odds ratio 2.20, 95% confidence interval 1.62-2.99; p < 0.001). Conversely, no statically significant association was recorded between history of heart-valve replacement and length of stay, estimated hospital cost, intraoperative complications, perioperative bleeding, vascular complications, infections, blood transfusions, CCT use, and in-hospital mortality. CONCLUSIONS: Radical cystectomy patients with history of heart-valve replacement exhibited a 2.2-fold higher risk of cardiac complications, but no other complications, including no significantly higher in-hospital mortality.

Surgically treated pelvic liposarcoma and leiomyosarcoma: The effect of tumor size on cancer-specific survival.

INTRODUCTION: In soft tissue pelvic liposarcoma and leiomyosarcoma, it is unknown whether a specific tumor size cut-off may help to better predict prognosis, defined as cancer-specific survival (CSS). We tested whether different tumor size cut-offs, could improve CSS prediction. MATERIALS AND METHODS: Surgically treated non-metastatic soft tissue pelvic sarcoma patients were identified (Surveillance, Epidemiology, and End Results 2004-2019). Kaplan-Meier plots, univariable and multivariable Cox-regression models and receiver operating characteristic-derived area under the curve (AUC) estimates were used. RESULTS: Overall, 672 (65 %) liposarcoma (median tumor size 11 cm, interquartile range [IQR] 7-16) and 367 (35 %) leiomyosarcoma (median tumor size 8 cm, IQR 5-12) patients were identified. The p-value derived ideal tumor size cut-off was 17.1 cm, in liposarcoma and 7.0 cm, in leiomyosarcoma. In liposarcoma, according to p-value derived cut-off, five-year CSS rates were 92 vs 83 % (≤17.1 vs > 17.1 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 83.8 to 86.8 % (Δ = 3 %). Similarly, among previously established cut-offs (5 vs 10 vs 15 cm), also 15 cm represented an independent predictor of CSS and improved prognostic ability from 83.8 to 87.0 % (Δ = 3.2 %). In leiomyosarcoma, according to p-value derived cut-off, five-year CSS rates were 86 vs 55 % (≤7.0 vs > 7.0 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 68.6 to 76.5 % (Δ = 7.9 %). CONCLUSIONS: In liposarcoma, the p-value derived tumor size cut-off was 17.1 cm vs 7.0 cm, in leiomyosarcoma. In both histologic subtypes, these cut-offs exhibited the optimal statistical characteristics (univariable, multivariable and AUC analyses). In liposarcoma, the 15 cm cut-off represented a valuable alternative.

Contemporary conditional cancer-specific survival rates in surgically treated nonmetastatic primary urethral carcinoma.

BACKGROUND: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in radical urethrectomy nonmetastatic primary urethral carcinoma (PUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, patient (age, sex, race/ethnicity, and marital status) and tumor (stage and histology) characteristics, as well as systemic therapy exposure status of nonmetastatic PUC patients were tabulated. Conditional survival estimates at 5-year were assessed based on DFI duration and according to stage at presentation (T1 -2N0 vs. T3-4N0-2). RESULTS: Of all 512 radical urethrectomy PUC patients, 278 (54%) harbored T1-2N0 stage versus 234 (46%) harbored T3-4N0-2 stage. In 512 PUC patients, 5-year CSM-free survival at initial diagnosis was 61.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 85.6%. In 278 T1-2N0 PUC patients, 5-year CSM-free survival at initial diagnosis was 68.4%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 86.9%. In 234 T3-4N0-2 PUC patients, 5-year CSM-free survival at initial diagnosis was 53.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 83.6%. CONCLUSIONS: Although intuitively, clinicians and patients are well aware of the concept that increasing DFI duration improves survival probability, only a few clinicians can accurately estimate the magnitude of survival improvement, as was done within the current study. Such information is crucial to survivors, especially in those diagnosed with rare malignancies, where the survival estimation according to DFI duration is even more challenging.

Prognostic significance of lymph node count in surgically treated patients with T2-4 stage nonmetastatic adrenocortical carcinoma.

PURPOSE: The role of lymphadenectomy and the optimal lymph node count (LNC) cut-off in nonmetastatic adrenocortical carcinoma (nmACC) are unclear. METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, surgically treated nmACC patients with T2-4 stages were identified between 2004 and 2020. We tested for cancer-specific mortality (CSM) differences according to pathological N-stage (pN0 vs. pN1) and two previously recommended LNC cut-offs (≥4 vs. ≥5) were tested in pN0 and subsequently in pN1 subgroups in Kaplan-Meier plots and multivariable Cox regression models. RESULTS: Of 710 surgically treated nmACC patients, 185 (26%) underwent lymphadenectomy and were assessable for further analyses based on available LNC data. Of 185 assessable patients, 152 (82%) were pN0 and 33 (18%) were pN1. In Kaplan-Meier analyses, CSM-free survival was 74 vs. 14 months (Δ 60 months, P ≤ 0.001) in pN0 vs. pN1 patients, respectively. In multivariable analyses, pN1 was an independent predictor of higher CSM (HR:3.13, P < 0.001). In sensitivity analyses addressing pN0, LNC cut-off of ≥4 was associated with lower CSM (multivariable hazard ratio [HR]: 0.52; P = 0.002). In sensitivity analyses addressing pN0, no difference was recorded when a LNC cut-off of ≥5 was used (HR:0.60, P = 0.09). In pN1 patients, neither of the cut-offs (≥4 and ≥5) resulted in a statistically significant stratification of CSM rate, and neither reached independent predictor status (all P > 0.05). CONCLUSIONS: Lymphadenectomy provides a prognostic benefit in nmACC patients and identifies pN1 patients with dismal prognosis. Conversely, in pN0 patients, a LNC cut-off ≥4 identifies those with particularly favorable prognosis.