Search

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: 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 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 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 surgically treated adrenocortical carcinoma (ACC) patients.Within the Surveillance, Epidemiology, and End Results database (2004-2018), 867 ACC patients treated with adrenalectomy were identified. Conditional survival estimates at 5-years were assessed based on DFI duration and according to stage at presentation. Separate Cox regression models were fitted at baseline and according to DFI.Overall, 406 (47%), 285 (33%), and 176 (20%) patients were stage I-II, III and IV, respectively. In conditional survival analysis, providing a DFI of 24 months, 5-year CSM-free survival at initial diagnosis increased from 66% to 80% in stage I-II, from 35% to 66% in stage III, and from 14% to 36% in stage IV. In multivariable Cox regression models, stage III (hazard ratio [HR]: 2.38; p 0.001) and IV (HR: 4.67; p 0.001) independently predicted higher CSM, relative to stage I-II. The magnitude of this effect decreased over time, providing increasing DFI duration.In surgically treated ACC, survival probabilities increase with longer DFI duration. This improvement is more pronounced in stage III, followed by stages IV and I-II patients, in that order. Survival estimates accounting for DFI may prove valuable in patients counseling.

In primaries other than adrenocortical carcinoma (ACC), Hispanic race/ethnicity may predispose to higher stage at initial diagnosis and may result in worse survival. We tested the association between Hispanic race/ethnicity and cancer specific mortality (CSM) in ACC patients in addition to testing for differences in other-cause mortality (OCM) rates between Hispanics and Caucasians.Within Surveillance, Epidemiology, and End Results database (2004-2018), we identified 1,060 ACC patients: 167 (15.8%) Hispanics vs. 893 (84.2%) Caucasians. Propensity score matching (age, sex, grade, T, N and M stages, treatment types), cumulative incidence plots Poisson-smoothing and competing risk regression (CRR) were used.Compared to Caucasians, Hispanics were younger (51 vs. 57 years, p0.001) and presented higher rates of T3-4 primary tumor stage (52.7% vs. 42.8%, p=0.007). No other statistically significant differences were observed for grade, lymph node invasion, distant metastases, European Network for the Study of Adrenal Tumors (ENSAT) stage and treatment type (p0.05 in all cases). After matching (1:3), 167 Hispanics and 501 Caucasians remained and were included in CRR analyses. In Hispanics, five-year CSM rates were 38.0% and 78.8% in respectively ENSAT stages I-II and III-IV vs. 34.1% and 74.4% in Caucasians. Overall, five-year OCM rates were 10.7% vs. 9.0% in Hispanics and Caucasians, respectively. In multivariable CRR models, Hispanic race/ethnicity was not an independent predictor for higher CSM (hazard ratio=1.18, p=0.2).In ACC, relative to Caucasians, Hispanic race/ethnicity is associated with lower age at initial diagnosis, but not with higher tumor stage or survival disadvantage.

To assess the effect of event-free survival duration on cancer-specific mortality (CSM) after radical cystectomy (RC) in nonmetastatic muscle-invasive squamous cell carcinoma of the urinary bladder.RC patients treated for non-metastatic muscle-invasive squamous cell carcinoma of the urinary bladder were identified within the Surveillance, Epidemiology, and End Results database (2000-2018). Independent predictor status for CSM of T and N stage groupings (i.e., T2N0, T3N0, T4N0, and TanyN1-3) was tested in multivariable Cox-regression models. Conditional 5-year CSM-free estimates were assessed at baseline and at 4 specific event-free survival times (i.e. 6, 12, 18 and 24 months), within each of the 4 examined stage groups.Of 981 RC patients, 206 (21%), 416 (42%), 152 (16%), and 207 (21%) were T2N0, T3N0, T4N0, and TanyN1-3, respectively. In multivariable Cox-regression models T3N0 (HR 1.94), T4N0 (HR 5.22), and TanyN1-3 (HR 6.62) were independent predictors of CSM, relative to T2N0. In conditional survival analyses based on 24 months event-free status, survival estimates were: 89% for T2N0 vs. 76% at baseline (Δ = 13%), 84% for T3N0 vs. 58% at baseline (Δ = 26%), 69% for T4N0 vs. 25% at baseline (Δ = 44%), 69% for TanyN1-3 vs. 22% at baseline (Δ = 47%).Event-free status at 24 months of follow-up is associated with substantially higher CSM-free survival than when CSM-free survival is predicted at baseline. The magnitude of this effect is most pronounced in TanyN1-3 and T4N0 patients, intermediate in T3N0 and more modest, nonetheless important, in T2N0.

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.

The proposed international staging collaboration for cancer of the prostate (STAR-CAP) clinical prognostic system for prostate cancer predicts cancer-specific mortality (CSM) for patients for whom active treatment, such as radical prostatectomy (RP), is planned. Until now, no validation of STAR-CAP has been performed. We retrospectively analyzed data from our institutional database for 19 552 patients treated with RP between 1992 and 2015. We applied the STAR-CAP point assignment criteria to calculate total individual scores and then classified patients according to the STAR-CAP stage groups ranging from IA (lowest risk) to IIIC (highest risk). We evaluated biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS), and cancer-specific survival (CSS) stratified by STAR-CAP stage groups over 10 yr, calculated the area under the receiver operating characteristics curve (AUC), and performed decision curve analyses to assess the ability of STAR-CAP to predict these outcomes after fitting the data from our single-institution data set. STAR-CAP performed well in stratifying individual survival outcomes for BCR-free survival, MFS, and CSS for each stage group in Kaplan-Meier analyses (p 0.001 between groups). The AUC for prediction of BCR, metastasis, and CSM at 10 yr was 0.73, 0.84, and 0.75, respectively. Our findings validate the performance of STAR-CAP for European patients treated with RP. PATIENT SUMMARY: We validated the STAR-CAP system for predicting cancer outcomes after removal of the prostate. Our results show that the system performs well and could help in counseling patients with prostate cancer.

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.

SummaryBroadly 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.