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.

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.

Non-C19MC-altered embryonal tumor with multilayered rosettes in a young woman with DICER1 syndrome: case report and review of the literature.

Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive and therapy-resistant pediatric central nervous system (CNS) tumors that have three histological patters: embryonal tumor with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma. We present a case of ETMR in an 18-year-old woman with DICER1 syndrome. This report confirms the important role of DNA-methylation analysis in the classification of CNS embryonal tumors and the importance of investigating somatic and germline DICER1 mutations in all CNS embryonal tumors.

Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

BACKGROUND: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. METHODS: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). RESULTS: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). CONCLUSION: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.

OBJECTIVE: To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS. RESULTS: Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03). CONCLUSION: Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.

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.

Rare histological prostate cancer subtypes: Cancer-specific and other-cause mortality.

BACKGROUND: To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes. METHODS: Using the Surveillance, Epidemiology, and End Results database (2004-2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models. RESULTS: Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients. CONCLUSIONS: Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.

Survival of patients with lymph node versus bone versus visceral metastases according to CHAARTED/LATITUDE criteria in the era of intensified combination therapies for metastatic hormone-sensitive prostate cancer.

BACKGROUND: The first approvals of novel systemic therapies within recent years for metastatic hormone-sensitive (mHSPC) were mainly based on improved overall survival (OS) and time to castration resistance (ttCRPC) in mHSPC patients stratified according to CHAARTED low (LV) versus high volume (HV) and LATITUDE low (LR) versus high-risk (HR) disease. METHODS: Relying on our institutional tertiary-care database we identified all mHSPC stratified according to CHAARTED LV versus HV, LATITUDE LR versus HR and the location of the metastatic spread (lymph nodes (M1a) versus bone (M1b) versus visceral/others (M1c) metastases. OS and ttCRPC analyses, as well as Cox regression models were performed according to different metastatic categories. RESULTS: Of 451 mHSPC, 14% versus 27% versus 48% versus 12% were classified as M1a LV versus M1b LV versus M1b HV versus M1c HV with significant differences in median OS: 95 versus 64 versus 50 versus 46 months (p < 0.001). In multivariable Cox regression models HV M1b (Hazard Ratio: 2.4, p = 0.03) and HV M1c (Hazard Ratio: 3.3, p < 0.01) harbored significant worse than M1a LV mHSPC. After stratification according to LATITUDE criteria, also significant differences between M1a LR versus M1b LR versus M1b HR versus M1c HR mHSPC patients were observed (p < 0.01) with M1b HR (Hazard Ratio: 2.7, p = 0.03) and M1c HR (Hazard Ratio: 3.5, p < 0.01), as predictor for worse OS. In comparison between HV M1b and HV M1c, as well as HR M1b versus HR M1c no differences in ttCRPC or OS were observed. CONCLUSIONS: Significant differences exist between different metastatic patterns of HV and LV and HR and LR criteria. Best prognosis is observed within M1a LV and LR mHSPC patients.

Transition from Transrectal to Transperineal MRI-Fusion Prostate Biopsy Does Not Comprise Detection Rates of Clinically Significant Prostate Cancer at a Tertiary Care Center.

BACKGROUND: A remarkable paradigm shift has emerged regarding the preferred prostate biopsy approach, favoring the transperineal (TP) over the transrectal (TR) approach due to the reduced risk of severe urinary tract infections. However, its impact on the detection of clinically significant prostate cancer (csPCa) remains unclear. MATERIALS AND METHODS: We relied on a prospectively maintained tertiary care database to identify patients who underwent either TP or TR prostate biopsy between 01/2014 and 12/2023. Of those, only patients with suspicious magnetic resonance imaging (MRI) PIRADS lesions (Likert-scale: 3,4,5) received MRI-targeted and systematic biopsies. Detection rates of csPCa (International Society of Urological Pathology [ISUP] ≥ 2) were compared between biopsy approach (TP vs. TR) according to index lesion. Subsequently, uni- and multivariable logistic regression models were applied to investigate the predictive status of the biopsy approach within each subcohort. RESULTS: Of 2063 patients, 1118 (54%) underwent combined MRI-guided and systematic prostate biopsy and were included in the final cohort. Of those, 127 (11%) and 991 (89%) underwent TP vs. TR. CsPCa rates, regardless of differences in patients' demographics and distribution of index PIRDAS lesions, did not differ statistically significantly and were 51 vs. 52%, respectively (p = 0.8). CsPCa detection rates for PIRDAS-3, PIRADS-4 and PIRADS-5 did not differ and were 24 vs. 23%, 48 vs. 51% and 72 vs. 76% for PIRADS-3, PIRADS-4 and PIRADS-5 subgroups for TP vs. TR, respectively (all p ≥ 0.9) Conclusions: The current results support the available data indicating that TP biopsy approach is comparable to transrectal biopsy approach regarding csPCa detection rates.

Nerve-sparing radical prostatectomy using the neurovascular structure-adjacent frozen-section examination (NeuroSAFE): results after 20 years of experience.

OBJECTIVES: To evaluate the long-term oncological outcomes and functional results of the neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during nerve-sparing (NS) radical prostatectomy (RP). MATERIALS AND METHODS: A 10-yr survival analysis on 11069 RPs performed with or without the NeuroSAFE, between January 2002 to June 2011 was carried out. In the NeuroSAFE cohort, the neurovascular structure-adjacent prostatic margins are removed and stained for cryo-sectioning during RP. In case of a PSM, partial or full removal of the neurovascular bundle was performed. The impact of NeuroSAFE on biochemical recurrence-free survival (BFS), salvage radiation therapy-free survival, metastasis-free survival, and prostate cancer-specific survival at 10 years was analyzed. 1-year (1-yr) erectile function (EF), 1-yr, and 2-yr continence rates were assessed in propensity score-based matched cohorts. RESULTS: Median follow-up was 121 (IQR: 73, 156) months. No differences in BFS between NeuroSAFE and non-NeuroSAFE were recorded (10-yr BFS: NeuroSAFE vs non-Neurosafe, pT2: 81% vs 84%, p = 0.06; pT3a: 58% vs. 63%, p = 0.6; ≥pT3b: 22% vs. 27%, p = 0.99). No differences were found between the two groups in terms of sRFS (pT2: p = 0.1; pT3a: p = 0.4; ≥pT3b: p = 0.4) (Fig. 1B, Table 2), and MTS (pT2: p = 0.3; pT3a: p = 0.6; ≥pT3b: p = 0.9). The NeuroSAFE-navigated patients reported a better 1-yr EF than non-NeuroSAFE (68% vs. 58%, p = 0.02) and no differences in 1-yr and 2-yr continence rates (92.4% vs. 91.8%, and 93.4% vs. 93%, respectively). The main limitation is the retrospective study design. CONCLUSIONS: While the NeuroSAFE approach did not show significant improvements in long-term oncologic or continence outcomes, it did provide an opportunity for a higher proportion of patients to improve postoperative functional results, possibly through increased nerve-sparing procedures.

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.

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.

American Board of Emergency Medicine Report on Residency and Fellowship Training Information (2023-2024).

The American Board of Emergency Medicine gathers extensive background information on Accreditation Council of Graduate Medical Education-accredited emergency medicine residency and fellowship programs as well as the residents and fellows training in those programs. We present the 2024 annual report on the status of physicians training in ACGME-accredited emergency medicine training programs in the United States.

Treatment patterns and oncological outcomes of older adults with metastatic prostate cancer in real-world setting.

BACKGROUND: The landscape of systemic therapies for metastatic hormone-sensitive (mHSPC) and castration resistant prostate cancer (mCRPC) extensively improved within the last decades resulting in a significantly prolonged overall survival. However, subgroup analyses of phase III trials suggest potentially different overall survival outcomes for older adults. METHODS: We relied on our institutional metastatic prostate cancer database to identify mHSPC and subsequently mCRPC patients. Older adults were stratified according to age groups 70-74 versus ≥75-79 versus ≥80 years at metastatic occurrence. Subsequently, uni- and multivariable time to mCRPC and overall survival analyses were performed. RESULTS: Of 494 older adults, 217 (44%) were 70-74 versus 180 (36%) 75-79 versus 97 (20%) ≥80 years old. Rates of local prostate cancer treatment differed significantly between all three groups (p < 0.01). Regarding mHSPC treatment, androgen receptor signaling inhibitors (ARSI) were administered in 30-39% of patients and docetaxel with 9% in age group 70-74 years and 6% and 3% in age groups 75-79 years and ≥80 years. Regarding mCRPC treatment, significant differences between treatment proportions were observed (p < 0.01). Most common treatment was ARSI for all three groups. Conversely, chemotherapy was more frequently administered in patients aged 70-74 (16%), relative to 4% and 3% in 75-79 year and ≥80 year aged patients. In univariable and multivariable time to mCRPC analyses, overall survival in mHSPC and OS in mCRPC analyses, no significant differences between all three age groups were observed (all p ≥ 0.3). CONCLUSIONS: Treatment patterns differ significantly between older adults with metastatic prostate cancer. However, these differences may not result in differences of overall life expectancy.

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.

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).

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.

Central Nervous System Siderosis Associated with Multiple Cerebral Aneurysms: Literature Review and Description of an Additional Case.

BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare disease characterized by deposition of hemosiderin along the leptomeninges due to chronic or recurrent bleeding into the subarachnoid space. The association of unruptured intracranial aneurysm (IA) and cortical SS is quite rare. METHODS: A systematic literature review to assess possible commonalities and/or differences of previous reported cases was undertaken. We report an additional case from our institution. RESULTS: A 40-year-old woman presented with a history of generalized seizures over the past year. There was no clinical history suggestive of aneurysm rupture. Magnetic resonance imaging revealed 2 aneurysms of the right middle cerebral artery (MCA) bifurcation associated with hemosiderin deposition along the right sylvian fissure and a third aneurysm of the left MCA bifurcation. Magnetic resonance imaging showed wall enhancing thickening of the larger right MCA aneurysm. The patient underwent surgical clipping of all 3 MCA aneurysms in a staged procedure. Histological examination revealed hemosiderin deposits within the aneurysm wall and surrounding gliosis. CONCLUSIONS: Our literature review found 24 reported cases of unruptured IA associated with cortical SS. The possible source for leakages could be neovessels visible in IA walls. The case reported illustrates an uncommon presentation of recurrent bleeding from an IA as a source of SS. The presence of an apparently unruptured IA surrounded by cortical SS on imaging studies is of high relevance as this should be considered a sign of aneurysm wall instability and should indicate prompt treatment.

Impact of PSA nadir, PSA response and time to PSA nadir on overall survival in real-world setting of metastatic hormone-sensitive prostate cancer patients.

BACKGROUND: To evaluate the impact of prostate-specific antigen (PSA) nadir, PSA response and time to PSA nadir (TTN) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies. METHODS: Different PSA nadir cut-offs (including ultra-low PSA) were tested for OS analyses. Additionally, PSA response ≥99% was evaluated, as well as TTN categorized as <3 versus 3-6 versus 6-12 versus >12 months. Multivariable Cox regression models predicted the value of PSA nadir cut-offs, PSA response and TTN on OS. Sensitivity analyses were performed in de novo and high volume mHSPC patients. RESULTS: Of 238 eligible patients, PSA cut-offs of <0.2 versus 0.2-4.0 versus >4.0 ng/mL differed significantly regarding median OS (96 vs. 56 vs. 44 months, p < 0.01), as well as in subgroup analyses of de novo mHSPC patients and multivariable Cox regression models. A more stringent PSA cut-off of <0.02 versus 0.02-0.2 versus >0.2 ng/mL also yielded significant median OS differences (not reached vs. 96 vs. 50 months, p < 0.01), even after additional multivariable adjustment. A PSA response ≥99% was also significantly associated with better OS than counterparty with <99% response, even after multivariable adjustment (both p < 0.02). When TTN groups were compared, patients with longer TTN harbored more extended OS than those with short TTN (<3 vs. 3-6 vs. 6-12 vs. >12 months: 34 vs. 50 vs. 67 vs. 96 months, p < 0.01). Virtually similar results were observed in sensitivity analyses for high volume mHSPC patients. CONCLUSIONS: In times of combination therapies for mHSPC, a PSA nadir of respectively, <0.2 and <0.02 ng/mL are associated with best OS rates. Moreover, a relative PSA response ≥99% and a longer TTN are clinical important proxies for favorable OS estimates.

Fish stocks as phosphorus sources or sinks: Influenced by nutritional and metabolic variations, not solely by dietary content and stoichiometry.

The study provides a descriptive understanding of when fish (Cyprinus carpio model) are the source or sink of phosphorus. Dissolved reactive phosphorus (DRP; PO4-P) losses (51.1 ± 5.9 % of intake-P) increase at excess of bioavailable P (>0.83 g 100 g-1 dry matter, DM fed) or when food (digestible) N:P mass ratio (≤4.4:1) approaches organismal storage threshold (~4:1). This is known, however, even at a sub-threshold food P content (0.57 g 100 g-1 DM) and food N:P mass ratio (7.3:1), DRP losses (57.8 ± 4.5 % of intake-P) may be extraordinary if two indispensable amino acids are biologically insufficient (lysine ≤1.43 g, methionine ≤0.39 g 100 g-1 DM fed). Given that methionine and lysine are sufficient, DRP losses cease (≈0 %) and even some P from water is absorbed, given there is support from non-protein energy (NPE). Insufficient NPE (<180 kcal 100 g-1 DM fed) may drive DRP losses (81.6 ± 4.3 % of intake-P) beyond expected levels (46-59 % of intake-P) at a given food P content (0.91 g 100 g-1 DM). Natural food seldom fulfills low P, high lysine + methionine, and high NPE contents simultaneously, thus keeping fish in a perpetual P recycling for algae (scaleless carp > scaly carp). Such P recycling ceases only during basal metabolism. During feeding state, the richness of lysine + methionine bound N and lipid + carbohydrate bound C in the food base may enhance the fishes' threshold of P storage. P storage can be diminished when they are insufficient. We show that for fish, the decision of P recycling or not recycling (for algae) may change based on the supply of specific fractions of N or C from the food web or metabolic variations (basal metabolism, presence of scales). NOVELTY STATEMENT: The ecological stoichiometry theory is better connected to fish nutritional bioenergetics for better understanding and biomanipulation of eutrophication processes.