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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).)

Purpose: No currently available phase III trial compared docetaxel vs. androgen receptor pathway inhibitors (ARPI) regarding cancer-control outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Moreover, few is known about the effect of sequential therapies in mHSPC and subsequent metastatic castration resistant prostate cancer (mCRPC)., Methods: We relied on the FRAMCAP database and compared docetaxel vs. ARPI in mHSPC patients regarding time to mCRPC (ttCRPC) and overall survival (OS). Sensitivity analyses addressed high volume mHSPC patients. Finally, sequential therapies were compared regarding progression-free survival (PFS) and OS in first-line mCRPC., Results: Of 419 included mHSPC patients, 25% received docetaxel vs. 75% ARPI. ARPI patients were significantly older (71 vs. 66 years), and harbored lower baseline PSA (38 vs. 183 ng/ml, both p ≤ 0.002). Median ttCRPC was significantly longer for ARPI than for docetaxel-treated patients (30 vs. 17 months, hazard ratio [HR]: 0.49, p < 0.001). In OS analyses, ARPI patients also exhibited significantly longer OS, relative to docetaxel patients (96 vs. 50 months, HR: 0.67, p = 0.03). After multivariable adjustment in Cox regression models, no difference between both treatments remained in both analyses (all p > 0.05). In sensitivity analyses of high volume mHSPC patients only, also no ttCRPC or OS differences were observed for ARPI vs. docetaxel (all p > 0.05). Regarding sequential therapies, no PFS and OS differences were observed for all and specifically high volume mHSPC patients, when ARPI-ARPI vs. ARPI-docetaxel vs. docetaxel-ARPI treatments were compared (all p > 0.05)., Conclusion: In real-world setting, ARPI treatment performs comparable to docetaxel chemotherapy in mHSPC. Therefore, docetaxel should only be used in triplet therapy. Moreover, no differences for sequential therapies of ARPI/docetaxel combinations in first-line mCRPC were observed., Competing Interests: Declarations. Competing interests: Financial disclosures and Conflicts of interest: Mike Wenzel receives speaker honoraria or is consultant for Accord, Johnsen&Johnsen, Pfizer, MSD, Astra Zeneca, Ipsen, Benedikt Hoeh receives speaker honoraria or is consultant for Johnsen&Johnsen and Ipsen, Thomas Steuber receives speaker honoraria or is consultant for Amgen, Astellas, Astra Zeneca, Bayer, Johnson & Johnson, MSD, Novartis, Pfizer, Proteomedics, Sanofi, Markus Graefen receives speaker honoraria or is consultant for Intuitive Surgical, Metronic, Ipsen, Astellas, Johnson & Johnson und Takeda, Felix Chun receives speaker honoraria or is consultant for Astellas, AstraZeneca, Bayer, Johnson & Johnson, Lumenis, Molecular Health, Olympus, Pfizer, Philipp Mandel receives speaker honoraria or is consultant for AMGEN, Astellas, AstraZeneca, Bayer, IPSEN, Johnson & Johnson, MSD, Novartis, Orion, Pfizer. Conflicts of interest: Mike Wenzel receives speaker honoraria or is consultant for Accord, Johnsen&Johnsen, Pfizer, MSD, Astra Zeneca, Ipsen, Benedikt Hoeh receives speaker honoraria or is consultant for Johnsen&Johnsen and Ipsen, Thomas Steuber receives speaker honoraria or is consultant for Amgen, Astellas, Astra Zeneca, Bayer, Johnson & Johnson, MSD, Novartis, Pfizer, Proteomedics, Sanofi, Markus Graefen receives speaker honoraria or is consultant for Intuitive Surgical, Metronic, Ipsen, Astellas, Johnson & Johnson und Takeda, Felix Chun receives speaker honoraria or is consultant for Astellas, AstraZeneca, Bayer, Johnson & Johnson, Lumenis, Molecular Health, Olympus, Pfizer, Philipp Mandel receives speaker honoraria or is consultant for AMGEN, Astellas, AstraZeneca, Bayer, IPSEN, Johnson & Johnson, MSD, Novartis, Orion, Pfizer. Consent to participate: No informed consent was necessary according to the approval of the study by the ethic committee., (© 2024. The Author(s).)

Introduction: Adjuvant pembrolizumab versus placebo significantly improved disease-free survival (DFS) in renal cell carcinoma (RCC) patients at high risk of recurrence following nephrectomy in KEYNOTE-564 trial (NCT03142334). The objective of this study was to evaluate efficacy and safety of adjuvant pembrolizumab in a real-world setting., Methods: In this multicenter retrospective study, RCC patients receiving adjuvant pembrolizumab between 01/22 and 10/23 at seven tertiary referral centers were included. DFS and treatment safety were assessed., Results: 52 patients with RCC were included. 24 (46%), 5 (9.6 %), 22 (42%) and 1 (1.9%) patients were classified as intermediate to high risk (IR to HR), high risk (HR), M1 with no evidence of disease (M1NED) and unknown. At a median follow-up of 6 months, DFS rates at 6 months were 64.2% in the overall cohort. In subgroup analyses, M1NED patients demonstrated significantly lower DFS compared to non-metastatic (combined: IR to HR/ HR) patients (log rank: p=0.025). Regarding toxicity, grade 3 or higher adverse events occurred in 26% of patients. Treatment discontinuations were reported in 20% of the patients., Conclusion: Recurrence rates in the M1NED group remained high and occurred earlier in our real-world compared to KEYNOTE-564. Long-term toxicities were comparable to clinical trials data., (S. Karger AG, Basel.)

Aims: Adjuvant chemotherapy after radical cystectomy can reduce the risk of recurrence and death in advanced muscle-invasive urothelial bladder cancer (MIBC). Molecular subtypes have been shown to be associated with survival. However, their predictive value to guide treatment decisions is controversial and data to use subtypes as guidance for adjuvant chemotherapy is sparse. We aimed to assess survival rates based on MIBC consensus molecular subtypes with and without adjuvant chemotherapy., Methods: Gene expression profiles of 143 patients with MIBC undergoing radical cystectomy were determined from formalin-fixed, paraffin-embedded specimen to assign consensus molecular subtypes. Expression of programmed cell death ligand-1 (PD-L1) and immune cell infiltration were determined using multiplex immunofluorescence. Matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy on overall survival (OS) for molecular subtypes applying Kaplan-Meier and Cox regression survival analyses., Results: Samples were luminal papillary: 9.1% (n=13), luminal non-specified: 6.3% (n=9), luminal unstable: 4.9% (n=7), stroma-rich: 27.9% (n=40), basal/squamous (Ba/Sq): 48.9% (n=70) and neuroendocrine-like (NE-like): 2.8% (n=4). Ba/Sq tumours had the highest concentration of PD-L1+ tumour and immune cells. Patients with luminal subtypes had better OS than those with NE-like (HR 0.2, 95% CI 0.1 to 0.7, p<0.05) and Ba/Sq (HR 0.5, 95% CI 0.2 to 0.9, p<0.05). No survival benefit with adjuvant chemotherapy was observed for luminal tumours, whereas Ba/Sq had significantly improved survival rates with adjuvant chemotherapy. Retrospective design and sample size are the main limitations., Conclusion: Consensus molecular subtypes can be used to stratify patients with MIBC. Luminal tumours have the best prognosis and less benefit when receiving adjuvant chemotherapy compared with Ba/Sq tumours., Competing Interests: Competing interests: PW has received consulting fees and honoraria for lectures by Bayer, Janssen-Cilag, Novartis, Roche, MSD, Astellas Pharma, Bristol-Myers Squibb, Thermo Fisher Scientific, Molecular Health, Guardant Health, Sophia Genetics, Qiagen, Eli Lilly, Myriad, Hedera Dx and AstraZeneca. Research Support was provided by AstraZeneca and Roche. HTG Transcriptome Panel was funded by HTG Molecular Diagnostics. HR was on an advisory board of Bristol-Myers Squibb, received honoraria from Roche, Bristol-Myers Squibb, Janssen-Cilag, Novartis, AstraZeneca, MCI, CHOP GmbH and Diaceutics, received travel support from Philips, Roche, and Bristol-Myers Squibb, and received grants from Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: To test for differences in organ-confined pathological tumor stage (pT) and intermediate International Society of Urological Pathologists (ISUP) grade vs. nonorgan confined pT stage and high ISUP grade and biochemical recurrence (BCR) after radical prostatectomy (RP)., Methods: Relying on a tertiary-care database, prostate cancer patients undergoing RP between January 2014 and December 2021 were stratified according to their combination of pT stage and ISUP grade in RP specimens (pT2 ISUP4/5 vs. pT3/4 ISUP2 vs. pT3/4 ISUP3). As Active Surveillance is recommended in ISUP1, these patients were excluded. Moreover, patients with pT2 ISUP2/3 are known for their good prognosis and pT3/4 ISUP4/5 patients for their poor prognosis. Therefore, these patients were also excluded from analyses. Kaplan-Meier survival analyses and multivariable Cox regression models addressed BCR after RP., Results: Of 215 RP patients, 29 (13%) exhibited pT2 ISUP4/5 vs. 122 (57%) pT3/4 ISUP2 vs. 64 (30%) pT3/4 ISUP3 pathology. In survival analyses, 3-year BCR-free survival rates were 95% in pT2 ISUP4/5 vs. 88% in pT3/4 ISUP2 vs. 65% in pT3/4 ISUP3 patients (P < 0.001). In multivariable Cox regression models addressing BCR, pT3/4 ISUP3 pathology was associated with higher BCR rate relative to pT2 ISUP4/5 pathology (hazard ratio 3.42, 95% confidence interval 1.07-10.94; P = 0.039), but not pT3/4 ISUP2 pathology (P = 0.6)., Conclusion: Compared to prostate cancer patients with pT2 ISUP4/5 pathology, the combination of pT3/4 ISUP3 pathology is associated with higher risk of BCR after RP. In consequence, patients with pT3/4 ISUP3 pathology should be considered for a closer postoperative follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To test for differences in recovery of lower urinary tract symptoms (LUTS) between patients with storage-positive vs -negative symptoms after laser enucleation of the prostate (LEP)., Patients and Methods: Consecutive storage-positive (severe storage symptoms, International Prostate Symptom Score [IPSS] storage subscore >8) vs storage-negative patients treated with LEP (November 2017-September 2022) within our tertiary-care database were identified. Mixed linear models tested for changes in IPSS and quality of life (QoL) at 1, 3 and 12 months after LEP. Multiple linear regression models tested for LUTS and QoL recovery risk factors at 1, 3 and 12 months., Results: Of 291 study patients, 180 (62%) had storage-positive symptoms. There were no differences between storage-positive and -negative patients in mean adjusted total IPSS, IPSS-storage, IPSS-voiding and QoL at 12 months after LEP. In multiple linear regression models, storage-positive status was identified as a risk factor for higher IPSS at 1 month (β coefficient 2.98, P = 0.004) and 3 months (β coefficient 2.24, P = 0.04), as well as for more unfavourable QoL at 1 month (β coefficient 0.74, P = 0.006) and 3 months (β coefficient 0.73, P = 0.004) after LEP. Conversely, at 12 months there were no differences between storage-positive vs -negative patients., Conclusion: Storage-positive patients appear to experience similar long-term benefits from LEP compared to storage-negative patients. However, significant storage symptoms are associated with higher total IPSS and less favourable QoL at 1 and 3 months after LEP. These findings advocate for the consideration of LEP also in storage-positive cases with the need for thorough patient education especially in the initial post-LEP period., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Hormonal agents administered for metastatic castration-resistant prostate cancer (mCRPC) may lead to osteoporosis, skeletal events, reduced quality of life, and even reduced overall survival (OS). Bone-modifying agents may prevent those events but their effect on cancer-control outcomes remains uncertain. Relying on our institutional tertiary-care database, we explored the effect of bone-modifying agents (bisphosphonates such as zoledronic acid and denosumab) on OS and progression-free survival in patients with mCRPC with at least 1 bone metastasis using Kaplan-Meyer estimates and Cox regression models. Of 420 patients with mCRPC, 60% received bone-modifying agents who were younger (68 vs 69 years), with more systemic treatment lines for mCRPC (3 vs 2), and a higher proportion of initial de novo metastatic disease (72% vs 62%, all p ≤ .04) than patients without bone-modifying agents. In progression-free survival analyses, no significant differences were observed between both groups. In OS analyses, significant median OS differences were observed in favor of patients with bone-modifying agents (58 vs 45 months; hazard ratio [HR]: 0.66), even after multivariable adjustment (HR: 0.37; both p ≤ .01). In bone-modifying agent-stratified analyses, 57% received denosumab vs 43% bisphosphonates, with a significantly higher rate of Eastern Cooperative Oncology Group status of ≥2 in the bisphosphonates group. In progression-free and OS analyses, no significant differences were observed between bisphosphonates and denosumab patients, with numerically better results in progression-free survival analysis for denosumab after adjusting for covariates. The cumulative rate of osteonecrosis of the jaw at any treatment time was 12% in both groups and significantly decreased over time. Real-world data suggest a relatively low administration rate of bone-modifying agents in patients with osseous mCRPC. However, real-world data also suggest an OS benefit when bone-modifying agents are used, even after controlling for possible confounding patient and tumor characteristics., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Purpose: Temporal trends in and predictors of inpatient palliative care use in patients with metastatic renal cell carcinoma (mRCC) undergoing critical care therapy are unknown., Methods: Relying on the National Inpatient Sample (2008-2019), we identified mRCC patients undergoing critical care therapy, namely invasive mechanical ventilation, percutaneous endoscopic gastrostomy tube insertion, dialysis for acute kidney failure, total parenteral nutrition, or tracheostomy. Estimated annual percentage changes (EAPC) analyses and multivariable logistic regression models addressed inpatient palliative care use., Results: Of 3802 mRCC patients undergoing critical care therapy, 817 (21.5%) received inpatient palliative care. Overall, inpatient palliative care use increased from 4.9% to 31.5% between 2008 and 2019 (EAPC +9.2%). In subgroup analyses, the highest increase in inpatient palliative care use was observed in the Midwest (EAPC: +11.9%), in the South (EAPC +10.4%), and in teaching hospitals (EAPC +9.0%; all P ≤ .004). In logistic regression models, teaching hospital status (odds ratio [OR] 1.41) and contemporary year interval (OR 2.12; all P < .001) independently predicted higher inpatient palliative care rates. Conversely, hospital admission in the Northeast (OR 0.53) or in the South (OR 0.79; all P ≤ .03) was associated with lower inpatient palliative care rates than in the West., Conclusion: In mRCC patients, inpatient palliative care rates have improved over time, with the highest increase in hospitals in the Midwest and in the South. Moreover, admission to teaching hospitals or in the West is associated with higher inpatient palliative care rates. In consequence, regional disparities, as well as differences according to teaching hospital status represent targets to achieve comprehensive inpatient palliative care coverage in mRCC patients receiving critical care therapy., Competing Interests: Disclosure The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients., Methods: We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models., Results: Of 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05)., Conclusion: M1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes., (© 2024. The Author(s).)

Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR)., Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan-Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion., Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion ( p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion ( p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01-2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13-2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular ( p = 0.740) or perineural invasion ( p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion., Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR.

Background/Objectives : Progression to metastatic castration-resistant prostate cancer (mCRPC) is defined either biochemically, radiographically or both. Moreover, staging for mCRPC can be performed either conventionally or with molecular imaging such as prostate-specific membrane antigen computer tomography (PSMA-PET/CT). Methods : We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free (PFS) and overall survival (OS) outcomes regarding the cause of castration resistance and the staging modality used. Results : Overall, 35% progressed to mCRPC biochemically vs. 23% radiographically vs. 42% biochemically + radiographically. The PSA nadir in mHSPC (1.4 vs. 0.4 vs. 0.8 ng/mL) and PSA level at mCRPC progression (15 vs. 2 vs. 21 ng/mL, both p ≤ 0.01) were significantly higher for biochemical vs. radiographic vs. both progressed patients. In PFS and OS analyses, no significant differences were observed among all three compared groups. In the comparison of the staging used for progression to mCRPC, 67% received conventional vs. 33% PSMA-PET/CT, with higher metastatic burden in mHSPC and osseous lesions in mCRPC for conventionally staged patients (both p < 0.01). In PFS (15.3 vs. 10.1 months, hazard ratio [HR]: 0.75) and OS analyses (52.6 vs. 34.3 months, HR: 0.61, both p < 0.05), PSMA-PET/CT harbored better prognosis; however, this did not hold after multivariable adjustment. Similar results were observed for further analyses in second- and third-line mCRPC or patients with a PSA level of ≥2 ng/mL. Conclusions : The cause of progression to mCRPC seems not to influence cancer-control outcomes, despite important baseline tumor characteristic differences. The PSMA-PET/CT staging modality might be associated with better PFS and OS outcomes, possibly due to its more sensitive detection of progression or new metastatic lesions.

Purpose: We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used., Results: In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004)., Conclusion: We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management., Competing Interests: Disclosures The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024 The Japanese Urological Association.)

Introduction: Metachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset., Patients and Methods: We relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa., Results: Of 341 mmPCa patients, 8% harbored GS6 versus 41% versus 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 versus 54 versus 41 months for GS6 versus GS7 versus GS8-10 (P = .01). Moreover, median time to onset of metastases was 64 versus 44 months for pT1-2 versus pT3-4 mmPCa patients undergoing radical prostatectomy (P = .027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of < 24 versus 24-60 versus 60-120 versus ≥ 120 months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 versus 69 versus 97 months versus not reached (P < .01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS., Conclusion: Timing of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa., Competing Interests: Disclosure None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

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: 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., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Background and Objective: Currently available post hoc phase 3 trial-derived data suggest better cancer-control outcomes in apalutamide-treated metastatic hormone-sensitive prostate cancer (mHSPC) patients achieving an (ultra)low prostate-specific antigen (PSA) nadir. This study aims to validate ultralow PSA nadir cutoffs., Methods: Relying on an institutional prostate cancer database, 107 eligible patients were yielded. The currently available PSA nadir cutoffs (SWOG trial: <0.2 ng/ml; ultralow TITAN trial: ≤0.02 vs 0.02-0.2 vs >0.2 ng/ml) and PSA responses (≥99%) were tested for time to castration-resistant prostate cancer (ttCRPC) and overall survival (OS) in mHSPC patients treated with apalutamide. Finally, comparisons were made against abiraterone mHSPC treatment., Key Findings and Limitations: Overall, 107 mHSPC patients treated with apalutamide at a median age of 68 yr and baseline PSA of 29 ng/ml were included. The highest proportion of included patients (40.2%) achieved an ultralow PSA nadir of ≤0.02 ng/ml. Patients reaching the SWOG 9346-defined PSA nadir of <0.2 ng/ml and ultralow PSA nadir of ≤0.02 ng/ml harbored the longest time to metastatic castration-resistant prostate cancer (mCRPC) and OS (all p < 0.05). Moreover, 80% of mHSPC patients treated with apalutamide achieved a PSA response of ≥99%. These patients also harbored better time to mCRPC and OS outcomes, relative to patients with a <99% PSA response (both p < 0.05). In the second step of analyses, a comparison against abiraterone patients showed a significantly higher rate of achieving an ultralow PSA nadir of ≤0.02 ng/ml: 40.2% versus 8.8% for apalutamide versus abiraterone, resulting in a significantly longer ttCRPC for the apalutamide-treated (37 mo) than for the abiraterone-treated (22 mo) group (p = 0.001), even after multivariable adjustment and in sensitivity analyses for high-risk mHSPC patients only. The study is limited by its retrospective design., Conclusions and Clinical Implications: In the real-world setting, most mHSPC patients treated with apalutamide achieve an ultralow PSA nadir, which is associated with better cancer-control outcomes. Moreover, a PSA response of ≥99% predicts better outcomes. In head-to-head comparisons, apalutamide achieves better PSA kinetics and ttCRPC outcomes than abiraterone., Patient Summary: A prostate-specific antigen (PSA) nadir of <0.02 ng/ml and PSA responses ≥99% are associated with better cancer-control outcomes in metastatic hormone-sensitive prostate cancer patients treated with apalutamide., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) versus non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies., Materials and Methods: Within our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC versus ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium risk groups, Eastern Cooperative Oncology Group status, and sarcomatoid feature., Results: Of 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months versus not reached for ccmRCC versus nccmRCC patients (P = .6). Median PFS was 13 versus 15 months (P = .9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (hazard ratio [HR]: 1.23; P = .6) or a higher progression rate (HR: 1.0; P = 1.0)., Conclusion: In our real-world multi-institutional study, no differences in OS and PFS between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed., Competing Interests: Disclosure The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Background : Biochemical recurrence (BCR) represents the rise of prostate-specific antigen (PSA) levels after treatment with curative radical prostatectomy (RP) or radiation for prostate cancer. The objective of the current study was to test for the association between patient characteristics, namely age, body mass index (BMI), as well as prostate volume at surgery, and BCR after RP. Material and Methods : Within a tertiary care database, patients with prostate cancer treated with RP between January 2014 and June 2023 were included. Kaplan-Meier survival analyses and Cox regression models addressed BCR after RP according to patient characteristics. Results : Of 821 patients, the median age was 66 years (interquartile range [IQR] 61-71 years), BMI was 26.2 kg/m 2 (IQR 24.3-28.8 kg/m 2 ), and prostate volume was 40 cm 3 (IQR 30-55 cm 3 ). Median follow-up was 20 months. In survival analyses, the three-year BCR-free survival rates were 81 vs. 84 vs. 81% in patients aged ≤60 vs. 61-69 vs. 70 years ( p = 0.1). In patients with BMI < 25.0 vs. 25.0-29.9 vs. ≥30.0 kg/m 2 , the three-year BCR-free survival rates were 84 vs. 81 vs. 84% ( p = 0.7). In patients with prostate volume ≤40 vs. >40 cm 3 , the three-year BCR-free survival rates were 85 vs. 80% ( p = 0.004). In multivariable Cox regression models accounting for patient and pathologic tumor characteristics and adjuvant radiation therapy, a higher prostate volume independently predicted BCR as continuous (hazard ratio 1.012, 95% confidence interval 1.005-1.019; p < 0.001), as well as categorized the variable based on the median (hazard ratio 1.66, 95% confidence interval 1.17-2.36; p = 0.005). Conversely, neither age nor BMI were significantly associated with BCR after RP. Conclusions : The higher prostate volume independently predicted BCR after RP, but not age or BMI at surgery. Consequently, patients with an elevated prostate volume should be considered for closer postoperative follow-up.

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.

Objectives: To identify low cancer-specific mortality (CSM) risk lymph node-positive (pN1) radical prostatectomy (RP) patients., Methods: Within Surveillance, Epidemiology and End Results database (2010-2015) pN1 RP patients were identified. Kaplan-Meier plots and multivariable Cox-regression (MCR) models were used. Pathological characteristics were used to identify patients at lowest CSM risk., Results: Overall, 2197 pN1 RP patients were identified. Overall, 5-year cancer-specific survival (CSS) rate was 93.3%. In MCR models ISUP GG1-2 (hazard ratio [HR]: 0.12, p < 0.001), GG3 (HR: 0.14, p < 0.001), GG4 (HR: 0.35, p = 0.002), pT2 (HR: 0.27, p = 0.012), pT3a (HR: 0.28, p = 0.003), pT3b (HR: 0.39, p = 0.009), and 1-2 positive lymph nodes (HR: 0.64, p = 0.04) independently predicted lower CSM. Pathological characteristics subgroups with the most protective hazard ratios were used to identify low-risk (ISUP GG1-3 and pT2-3a and 1-2 positive lymph nodes) patients versus others (ISUP GG4-5 or pT3b-4 or ≥3 positive lymph nodes). In Kaplan-Meier analyses, 5-year CSS rates were 99.3% for low-risk (n = 480, 21.8%) versus 91.8% (p < 0.001) for others (n = 1717, 78.2%)., Conclusions: Lymph node-positive RP patients exhibit variable CSS rates. Within this heterogeneous group, those at very low risk of CSM may be identified based on pathological characteristics, namely ISUP GG1-3, pT2-3a, and 1-2 positive lymph nodes. Such stratification scheme might be of value for individual patients counseling, as well as in design of clinical trials., (© 2024 Wiley Periodicals LLC.)

Introduction: It is unknown whether specific locations of visceral metastatic sites affect overall survival (OS) of metastatic prostate cancer (mPCa) patients. We tested the association between specific locations of visceral metastatic sites and OS in mPCa patients., Materials and Methods: Within Surveillance, Epidemiology and End Results database (2010-2016), survival analyses relied on specific locations of visceral metastases: lung only vs. liver only vs. brain only vs. ≥2 visceral sites. Kaplan-Meier plots and Cox regression models were fitted., Results: Of 1827 patients, 1044 (57%) harbored lung only visceral metastases vs. 457 (25%) liver only vs. 131 (7%) brain only vs. 195 (11%) ≥2 visceral sites. Median OS was 22 months in all patients vs. 33 months in lung only vs. 15 months in liver only vs. 16 months in brain only vs. 15 months in patients with ≥2 visceral sites. Highest OS was recorded in lung only visceral metastases patients, especially when concomitant nonvisceral metastases were located in lymph nodes only (median OS 57 months) vs. bone only (26 months) vs. lymph nodes and bone (28 months). Liver only, brain only or ≥2 visceral sites exhibited poor OS, regardless of concomitant nonvisceral metastases type (median OS from 13 to 19 months)., Conclusion: In mPCa patients, lung only visceral metastases, especially when associated with lymph node only nonvisceral metastases, portend the best prognosis. Conversely, visceral metastatic sites other than lung portend poor prognosis, regardless of concomitant nonvisceral metastases type., (Copyright © 2023 Elsevier Inc. All rights reserved.)