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To test for rates of inpatient palliative care (IPC) in metastatic testicular cancer patients receiving critical care therapy (CCT). Within the Nationwide Inpatient Sample (NIS) database (2008-2019), we tabulated IPC rates in metastatic testicular cancer patients receiving CCT, namely invasive mechanical ventilation (IMV), percutaneous endoscopic gastrostomy tube (PEG), dialysis for acute kidney failure (AKF), total parenteral nutrition (TPN) or tracheostomy. Univariable and multivariable logistic regression models addressing IPC were fitted. Of 420 metastatic testicular cancer patients undergoing CCT, 70 (17%) received IPC. Between 2008 and 2019, the rates of IPC among metastatic testicular cancer patients undergoing CCT increased from 5 to 19%, with the highest rate of 30% in 2018 (EAPC: + 9.5%; 95% CI + 4.7 to + 15.2%; p = 0.005). IPC patients were older (35 vs. 31 years, p = 0.01), more frequently had do not resuscitate (DNR) status (34 vs. 4%, p < 0.001), more frequently exhibited brain metastases (29 vs. 17%, p = 0.03), were more frequently treated with IMV (76 vs. 53%, p < 0.001) and exhibited higher rate of inpatient mortality (74 vs. 29%, p < 0.001). In multivariable analyses, DNR status (OR 10.23, p < 0.001) and African American race/ethnicity (OR 4.69, p = 0.003) were identified as independent predictors of higher IPC use. We observed a significant increase in rates of IPC use in metastatic testicular cancer patients receiving CCT, rising from 5 to 19% between 2008 and 2019. However, this rates remain lower compared to metastatic lung cancer patients, indicating the need for further awareness among clinicians treating metastatic testicular cancer. The increase in IPC rates for metastatic testicular cancer patients receiving CCT indicates a need for ongoing education and awareness among healthcare providers. This could enhance the integration of IPC in the treatment of advanced cancer, potentially improving quality of life and care outcomes for survivors., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: All analyses and their reporting followed the National (Nationwide) Inpatient Sample (NIS) reporting guidelines. Due to the anonymously coded design of the NIS database, study-specific Institutional Review Board ethics approval was not required., (© 2025. The Author(s).)

Background/objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes., Methods: Within the SEER database (2000-2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality., Results: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9-15.9 cm HR: 1.6; ≥16 cm HR: 1.9)., Conclusions: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status.

Background/Objectives : The impact of surgical resection versus non-resection on cancer-specific mortality (CSM) in soft tissue pelvic sarcoma remains largely unclear, particularly when considering histologic subtypes such as liposarcoma, leiomyosarcoma, and sarcoma NOS. The objective of the present study was to first report data regarding the association between surgical resection status and CSM in soft tissue pelvic sarcoma. Methods : Using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019, we identified 2491 patients diagnosed with pelvic soft tissue sarcoma. Cumulative incidence plots were used to illustrate CSM and other-cause mortality rates based on the histologic subtype and surgical resection status. Competing risk regression models were employed to assess whether surgical resection was an independent predictor of CSM in both non-metastatic and metastatic patients. Results : Among the 2491 patients with soft tissue pelvic sarcoma, liposarcoma was the most common subtype (41%), followed by leiomyosarcoma (39%) and sarcoma NOS (20%). Surgical resection rates were 92% for liposarcoma, 91% for leiomyosarcoma, and 58% for sarcoma NOS in non-metastatic patients, while for metastatic patients, the rates were 55%, 49%, and 23%, respectively. In non-metastatic patients who underwent surgical resection, five-year CSM rates by histologic subtype were 10% for liposarcoma, 32% for leiomyosarcoma, and 27% for sarcoma NOS. The multivariable competing risk regression analysis showed that surgical resection provided a protective effect across all histologic subtypes in non-metastatic patients (liposarcoma HR: 0.2, leiomyosarcoma HR: 0.5, sarcoma NOS HR: 0.4). In metastatic patients, surgical resection had a protective effect for those with leiomyosarcoma (HR: 0.6) but not for those with sarcoma NOS. An analysis for metastatic liposarcoma was not possible due to insufficient data. Conclusions: In non-metastatic soft tissue pelvic sarcoma, surgical resection may be linked to a reduction in CSM. However, in metastatic patients, this protective effect appears to be limited primarily to those with leiomyosarcoma.

Background: In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients., Patients and Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM)., Results: Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P < 0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P < 0.001) were independent predictors of higher OM, relative to good prognosis group., Conclusions: The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

All primary urinary tract malignant melanoma (ureter vs. bladder vs. urethra) patients were identified from within the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020. Kaplan-Maier plots depicted the overall survival (OS) rates. Univariable and multivariable Cox regression (MCR) models were fitted to test the differences in overall mortality (OM). In the overall cohort (n = 74), the median OS was 22 months. No statistically significant or clinically meaningful differences were recorded according to sex (female vs. male; p = 0.9) and treatment of the primary (endoscopic vs. surgical; p = 0.6). Conversely, clinically meaningful but not statistically significant ( p ≥ 0.05) differences were recorded according to the patient's age at diagnosis (≤80 vs. ≥80 years old; p = 0.2), marital status (married 26 vs. unmarried 16 months; p = 0.2), and SEER stage (localized 31 vs. regional 14 months; p = 0.4), and the type of systemic therapy (exposed 31 vs. not exposed 20 months; p = 0.06). Finally, in univariable and MCR analyses, after adjustment for the SEER stage and type of systemic therapy, tumor origin within the bladder was associated with a three-fold higher OM (Hazard ratio: 3.00; p = 0.004), compared to tumor origin within the urethra. In conclusion, primary urinary tract malignant melanoma patients have poor survival. Specifically, tumor origin within the bladder independently predicted a higher OM, even after adjustment for the SEER stage and systemic therapy status.

Introduction: Despite advances in treatment, metastatic urothelial carcinoma of the urinary bladder (mUCUB) is associated with high mortality and treatment risk. We tested for regional differences in mUCUB within a large-scale, population-based database., Methods: Using the Surveillance, Epidemiology and End Results (SEER) database (2010-2018), patient (age, sex, race/ethnicity), tumor (T-stage, N-stage, number of metastatic sites), and treatment (systemic therapy, radical cystectomy) characteristics were tabulated for mUCUB patients according to 11 SEER registries. Multinomial regression models and multivariable Cox regression models tested overall mortality (OM), adjusting for patient, tumor and treatment characteristics., Results: In 4817 mUCUB patients, registry-specific patient counts ranged from 1855 (38.5%) to 105 (2.2%). Important inter-regional differences existed for race/ethnicity (3-36% for others than non-Hispanic Whites), N-stage (28-39% for N1-3, 44-58% in N0, 8-22% for unknown N-stage), systemic therapy (38-54%) and radical cystectomy (3-11%). In multivariable analyses adjusting for these patient, tumor, and treatment characteristics, one registry exhibited significantly lower OM (SEER registry 10: hazard ratio [HR] 0.83) and two other registries exhibited significantly higher OM (SEER registries 9: HR 1.13; SEER registry 8: HR 1.24) relative to the largest reference registry (n=1855)., Conclusions: We identified important regional differences that included patient, tumor, and treatment characteristics. Even after adjustment for these characteristics, important OM differences persisted, which may warrant more detailed investigation.

Aim and Objectives : We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials : We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results : Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three ( p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion : Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

Background: Guidelines recommend VENUSS and GRANT models for the prediction of cancer control outcomes after nephrectomy for nonmetastatic papillary renal cell carcinoma (pRCC)., Objective: To test the ability of VENUSS and GRANT models to predict 5-yr cancer-specific survival in a North American population., Design Setting and Participants: For this retrospective study, we identified 4184 patients with unilateral surgically treated nonmetastatic pRCC in the Surveillance, Epidemiology, and End Results database (2004-2019)., Outcome Measurements and Statistical Analysis: The original VENUSS and GRANT risk categories were applied to predict 5-yr cancer-specific survival. A cross-validation method was used to test the accuracy and calibration of the models and to conduct decision curve analyses for the study cohort., Results and Limitations: The VENUSS and GRANT categories represented independent predictors of cancer-specific mortality. On cross-validation, the accuracy of the VENUSS and GRANT risk categories was 0.73 and 0.65, respectively. Both models showed good calibration and performed better than random predictions in decision curve analysis. Limitations include the retrospective nature of the study and the absence of a central pathological review., Conclusion: VENUSS risk categories fulfilled prognostic model criteria for predicting cancer-specific survival 5 yr after surgery in North American patients with nonmetastatic pRCC as recommended by guidelines. Conversely, GRANT risk categories did not. Thus, VENUSS risk categories represent an important tool for counseling, follow-up planning, and patient selection for appropriate adjuvant trials in pRCC., Patient Summary: We tested the ability of two validated methods (VENUSS and GRANT) to predict death due to papillary kidney cancer in a North American population. The VENUSS risk categories showed good performance in predicting 5-year cancer-specific survival., (© 2023 The Authors.)

Background: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown., Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients., Patients and Methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan-Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS)., Results: Of 853 SRP patients, 87% ( n = 727) underwent LND, and 21% ( n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 ( p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% ( p < 0.001), and CSS rates were 94% vs. 96% vs. 82% ( p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001)., Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

We aimed to externally validate the SEER-based nomogram used to predict downgrading in biopsied high-risk prostate cancer patients treated with radical prostatectomy (RP) in a contemporary European tertiary-care-hospital cohort. We relied on an institutional tertiary-care database to identify biopsied high-risk prostate cancer patients in the National Comprehensive Cancer Network (NCCN) who underwent RP between January 2014 and December 2022. The model's downgrading performance was evaluated using accuracy and calibration. The net benefit of the nomogram was tested with decision-curve analyses. Overall, 241 biopsied high-risk prostate cancer patients were identified. In total, 51% were downgraded at RP. Moreover, of the 99 patients with a biopsy Gleason pattern of 5, 43% were significantly downgraded to RP Gleason pattern ≤ 4 + 4. The nomogram predicted the downgrading with 72% accuracy. A high level of agreement between the predicted and observed downgrading rates was observed. In the prediction of significant downgrading from a biopsy Gleason pattern of 5 to a RP Gleason pattern ≤ 4 + 4, the accuracy was 71%. Deviations from the ideal predictions were noted for predicted probabilities between 30% and 50%, where the nomogram overestimated the observed rate of significant downgrading. This external validation of the SEER-based nomogram confirmed its ability to predict the downgrading of biopsy high-risk prostate cancer patients and its accurate use for patient counseling in high-volume RP centers.

Within the Surveillance, Epidemiology, and End Results database (2000-2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC.

Background and Objectives : The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database. Materials and Methods : We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality. Results : Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%; p < 0.01) and stage II (0.5 vs. 3.4%, p < 0.01), but not in stage I (0.9 vs. 1.6%, p = 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71, p = 0.01) and stage II (hazard ratio 0.11, p < 0.01). Conclusions : Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival.

We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens were identified within the Surveillance, Epidemiology, and End Results database (2004-2019). Kaplan-Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%, p < 0.001; stage II: 100 vs. 95.9%, p < 0.001; stage III: 66.8 vs. 77.8%, p = 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%; p < 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%; p = 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83; p < 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92; p = 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM.

We aimed at assessing the impact of non-urothelial variant histology (VH), relative to urothelial carcinoma of the urinary bladder (UCUB), on cancer-specific mortality (CSM) in T2N0M0 bladder cancer patients treated with trimodal therapy (TMT). TMT patients treated for T2N0M0 bladder cancer were identified within the Surveillance, Epidemiology, and End Results database (2000−2018). Patients who underwent TMT received trans-urethral resection of the bladder tumor, chemotherapy, and radiotherapy. CSM-FS rates were tested using Kaplan−Meier plots and multivariable Cox-regression (MCR) models according to histological subtype: UCUB vs. neuroendocrine carcinoma vs. squamous cell carcinoma vs. adenocarcinoma. A total of 3846 T2N0MO bladder cancer patients treated with TMT were identified. Of these, 3627 (94.3%) harbored UCUB, while 105 (2.7%), 85 (2.2%), and 29 (0.8%) harbored neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma, respectively. In Kaplan−Meier analyses, 3-yr CSM-FS rates were 57% for UCUB, 51% for neuroendocrine carcinoma, 35% for squamous cell carcinoma, and 60% for adenocarcinoma (p-value < 0.0001). In MCR models, only squamous cell carcinoma exhibited higher CSM than UCUB (HR 1.98, 95%CI 1.5−2.61, p-value < 0.001). Despite the small number of observations, squamous cell carcinoma distinguished itself from UCUB based on worse survival in T2N0M0 patients after TMT.

Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.