bluuebunny/crossref_metadata_2025 huggingface dataset:
Cadonilimab combined with lenvatinib for neoadjuvant therapy in early-stage renal cell carcinoma with indications for partial nephrectomy but high surgical risk: A prospective single-arm phase II clinical trial.
Authors: Peng Yulu , Dong Pei , Han Hui , Zhou Fangjian , Zhang Zhiling
Published: February 2025

530

Background:
Partial nephrectomy is the standard treatment for early-stage renal cell carcinoma; however, in some patients, although the tumor is early-stage, the surgical difficulty may preclude its implementation. This study aims to evaluate the efficacy and safety of Cadonilimab combined with Lenvatinib in neoadjuvant therapy for renal cell carcinoma with indications for partial nephrectomy but high surgical risk.
Methods:
This is a single-center, single-arm Phase II clinical trial. Eligible patients included those with biopsy-confirmed clear cell renal carcinoma who had indications for partial nephrectomy but were at high surgical risk (criteria: 1. tumors measuring 4-7 cm located at the renal hilum or endophytic ≥75%; 2. tumors larger than 7 cm). Patients received Lenvatinib at a dosage of 8 mg or 12 mg QD combined with Cadonilimab at 6 mg/kg every two weeks for 3-6 cycles, for a total treatment duration of 6-12 weeks. Cadonilimab is a first-in-class bispecific antibody targeting both PD-1 and CTLA-4. All patients are scheduled to undergo partial nephrectomy after neoadjuvant therapy. The primary endpoint was the objective response rate (ORR) based on RECIST 1.1 criteria. Secondary endpoints included the renal preservation success rate, safety, and incidence of perioperative complications.
Results:
A total of 27 patients were enrolled in the study. Sixteen patients completed 6 cycles of Cadonilimab treatment, 6 patients completed 3 cycles, and 5 patients did not complete the pre-set treatment cycles. One patient underwent surgery after experiencing a grade 4 adverse event (diabetic ketoacidosis) following the second cycle of Cadonilimab; four patients discontinued treatment for subjective reasons and proceeded to surgery after the second cycle. All 27 patients underwent surgical procedures. The primary endpoint ORR was 55.6% (15/27), with a tumor control rate of 100%. All patients demonstrated tumor reduction prior to nephrectomy, with an average maximum tumor diameter reduction rate of 26.5%. Furthermore, 100% of patients completed partial nephrectomy. Two patients achieved pathological complete response, and all patients exhibited tumor necrosis, with an average tumor necrosis rate of 45%. Adverse events (AEs) of grade ≥3 occurred in 10.5% of patients, including hyperglycemia and elevated ALT/AST. One patient experienced a grade 4 AE, and no grade 3 postoperative complications were reported. The main limitation of this study is that it is a single-center, small-sample study.
Conclusions:
Cadonilimab combined with Lenvatinib for neoadjuvant treatment in early clear cell renal carcinoma with indications for partial nephrectomy but high surgical risk demonstrates clear efficacy and safety, warranting further clinical validation. Clinical trial information:
NCT06138496
.
Efficacy of selective renal tumor embolization combined with axitinib and reduced-dose toripalimab in oligometastatic clear cell renal carcinoma: A comparative analysis with axitinib combined with standard-dose toripalimab.
Authors: Du Jun , Chen Feiran , Zhang Chao , Tian Jie , Zhang Li , Yang Qing , Yao Xin
Published: February 2025

532

Background:
Oligometastatic renal cell carcinoma (RCC) involves limited metastases (1-5) and lies between localized and metastatic disease, with lower tumor burden. Studies suggest these patients may respond well to local or systemic therapies like targeted or immunotherapy. Combining renal tumor embolization with these therapies is emerging as a promising option. However, comparative data on embolization versus non-embolization treatments remain scarce. This study compares efficacy and adverse events of these treatments in oligometastatic RCC using propensity score matching.
Methods:
This study included oligometastatic clear cell RCC patients treated since March 2023, divided into two groups. The experimental group received renal tumor embolization, axitinib (5 mg twice daily), and reduced-dose toripalimab (160 mg every 3 weeks). The control group received standard axitinib and toripalimab (240 mg every 3 weeks). All patients had their first follow-up three months post-treatment to assess efficacy and adverse effects. Propensity score matching (PSM) was used to balance demographics, tumor characteristics, and treatment history. The primary outcomes were disease control rate (DCR) and partial response rate (PR), with secondary outcomes being grade 3-4 adverse events.
Results:
58 patients were included, 29 in each group after matching. All covariates had SMD values < 0.1, indicating good baseline balance. The experimental group had a DCR of 100% and PR of 93.1%, compared to DCR of 69.8% and PR of 56.7% in the control group (P < 0.05). In 4 patients with renal vein tumor thrombus, tumor size reduced by over 50%, and thrombus control was effective. Grade 3-4 adverse events were lower in the experimental group (10.1% vs. 38.4%, P < 0.05), mainly hypertension, hand-foot syndrome, and liver dysfunction.
Conclusions:
Propensity score matching showed that renal tumor embolization combined with axitinib and reduced-dose toripalimab improved efficacy and reduced grade 3-4 adverse events in oligometastatic RCC patients. Larger randomized trials are needed to confirm these findings and explore personalized treatment strategies to improve long-term survival and quality of life.
Evaluating the efficacy of cabozantinib in patients with advanced renal cell carcinoma with bone metastasis: An open-label phase 2 study.
Authors: Hongo Fumiya , Nakai Yasutomo , Nozawa Masahiro , Kato Taigo , Kamikawa Sadanori , Tamada Satoshi , Yamada Kaori , Soeda Junpei , Tsubouchi Ryoichi , Osaka Tsuyoshi , Uemura Hirotsugu
Published: February 2025

535

Background:
Bone metastasis negatively impacts patients with advanced renal cell carcinoma (aRCC), leading to poor prognosis and quality of life. Some tyrosine kinase inhibitors, including cabozantinib, have been used as standard care for aRCC. However, there have been no reports demonstrating the effects of cabozantinib on bone metastasis. Here, we report the clinical effects of cabozantinib on bone metastasis in patients with aRCC.
Methods:
Patients with aRCC who had at least one measurable bone target lesion were enrolled. Patients received cabozantinib 60 mg once daily until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) of bone target lesions based on independent review committee (IRC) assessment using the MD Anderson Cancer Center (MDA) criteria, which are the response criteria specific to bone metastases. Key secondary endpoints included disease control rate (DCR), bone metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), frequency of symptomatic skeletal events (SSE) and safety.
Results:
In total, 31 patients were enrolled, with a median age of 70.0 years, and most patients (77.4%) had a history of systemic treatments for aRCC. All patients had bone metastasis. The ORR of bone target lesions by IRC-assessed MDA criteria was 6.5% (90% CI: 1.2–18.9), with a disease control rate (DCR) of 90.3% (90% CI: 76.8–97.3). No progressive disease was observed. The median BMFS was not reached (95% CI: 11.5–NR). The median PFS and OS were 11.9 (95% CI: 5.7–NR) months and 24.9 (95% CI: 19.1–NR) months, respectively. Three patients (9.7%) experienced SSE. No new safety concerns were identified.
Conclusions:
Cabozantinib demonstrated favorable clinical effects on bone metastasis in patients with aRCC, as suggested by a high DCR. Our results may provide useful insights for selecting optimal treatments for the management of aRCC with bone metastasis. Clinical trial information:
jRCTs031210220
.
The evaluation of therapeutic outcomes of percutaneous US/CT-guided bipolar radiofrequency ablation for small renal masses under local anesthesia.
Authors: Sun Yifan , Wei Wang , Hongqian Guo
Published: February 2025

556

Background:
This study is to evaluate the safety and feasibility of local anesthesia (LA) for percutaneous ultrasound/computed tomography (US/CT)-guided bipolar radiofrequency ablation (RFA) for small renal masses (SRMs) by comparing the LA with general anesthesia.
Methods:
A retrospective review was carried out between 2018 to 2023, 212 patients with SRMs were treated with US/CT-guided bipolar RFA. General anesthesia (GA) was performed in 91 and LA was performed in 121 patients. Demographics, tumor characteristics, peri-procedural data, pathologic and follow-up outcomes were analyzed. The factors associated with pain were also identified.
Results:
There was no significant difference in demographics and tumor characteristics between the LA and GA group. Several statistically significant decrease were observed in terms of procedural time (
P
<0.001), hospital stays (
P
<0.001) and hospital costs (
P
<0.001). The maximum perceived pain in LA group comprised 57.9% (70 of 121) mild, 42.1% (51 of 121) moderate. The anxiety in LA group comprised 62.0% (75 of 121) mild, 36.3% (44 of 121) moderate, 1.7% (2 of 121) severe. On multivariate analysis, tumor diameter was a significant predictor for pain in RFA procedure (OR 1.470,
P
<0.001). All patients were followed up for a median (range) of 36 (12-48) months. Local recurrence occurred in 15.7% (19 of 121) of the LA group and in 13.2% (12 of 91) in GA group (
P
=1.000). Moreover, there was no significant difference in the difference between postoperative eGFR and preoperative eGFR when comparing the two groups.
Conclusions:
Percutaneous bipolar RFA of SRMs using CT and ultrasound guidance under LA can be an effective and tolerable method for patients who are unfit for surgery and provide satisfactory oncologic control.
Mass cytometry-based deep immune cell profiling of metastatic clear cell renal cell carcinoma patients refractory to combined immune checkpoint and tyrosine kinase inhibitor therapy.
Authors: Formisano Luigi , Belli Stefania , Vallefuoco Angela , Pecoraro Giovanna , Migliaccio Fortuna , Barraco Chiara , Scipilliti Arianna , Esposito Daniela , Attanasio Giovanna , Hameetman Marjolijn , Tak Tamar , Lopez Ernesto , Scagliarini Sarah , Servetto Alberto , Bianco Roberto
Published: February 2025

576

Background:
Combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) improved outcomes for patients with metastatic clear cell renal cell carcinoma (mccRCC). However, some patients experience rapid disease progression. Identifying specific immune phenotypes and predictive circulating biomarkers is essential for the early detection of patients who may be refractory to ICI-TKI therapy.
Methods:
Serum samples and peripheral blood mononuclear cells (PBMCs) were collected from patients classified as complete responders (CR, n=4), partial responders (PR, n=10), and non-responders (NR, n=8) after 15 days (T1) and 1 month (T2) of nivolumab (ICI) and cabozantinib (TKI) therapy. Serum cytokines were analyzed using LEGENDplex, while PBMC immunophenotyping was performed using CyTOF to assess 37 immune cell populations and T cell markers related to activation, migration, and exhaustion.
Results:
In both responding and non-responding patients a common significant 90% reduction of PD1+TM3-CD8+ cells (p=0.0096 and p=0.0001, in CR and NR, respectively) and dendritic cells (decrease of 47% p=0.0004 in CR, 70% p=0.0059 in PR and 62% decrease p=0.0396 in NR) following therapy was observed. PD1+ Treg cells decreased significantly (93% decrease, p=0.0068) only in the CR after therapy. Additionally, CRs exhibited higher levels of exhausted PD1+ Treg cells (2.88 fold, p=0.0084) at baseline and an increased number of pro-inflammatory CD4+ Th2 cells (2 fold, p=0.0170) after one month compared to the other groups. PRs and NRs showed lower levels of natural killer cells (2.2 fold, p=0.0069), and a significant decrease of monocytes populations after therapy (45% decrease p=0.0008 in PRs, 40% decrease p=0.0012 in NRs). The CRs exhibited elevated levels of IL-23 (18 fold higher vs. NRs and 3 fold higher vs. PRs, p= 0.0094; p=0.0011) and IL-27 at baseline , and higher IL-15 and IL-18 levels post-therapy compared to the PR and NR. Kaplan-Meier plot analysis indicated that higher IL-23 levels correlated with an improved probability of PFS in all cancer patients treated with nivolumab (2.97 vs. 29.7 months in low vs. high expression cohorts; HR= 0.53 [95% CI 0.33 - 0.85], log-rank P = 0.0074).
Conclusions:
Our results suggest that patient’s initial immune profile might be significant predictor of treatment success and the likelihood of developing resistance.
Nectin-4 and Trop-2 expression as potential therapeutic target in collecting duct carcinoma: Preliminary results from the CICERONE trial (NCT05372302).
Authors: Procopio Giuseppe , Rametta Alessandro , Stellato Marco , de Braud Filippo Guglielmo Maria , Todoerti Katia , Agnelli Luca , Huber Veronica , Rivoltini Licia , Rollo Luisa , Vela Chiara , Claps Melanie , Guadalupi Valentina , Gusmaroli Eleonora , Rota Simone , Caliò Anna , Martignoni Guido , Verzoni Elena , Brunelli Matteo
Published: February 2025

587

Background:
Collecting Duct Carcinoma (CDC) represents 1% of all renal cell carcinomas (RCC) and is characterized by aggressive clinical behavior and a particularly dismal prognosis. Cabozantinib and platinum-based chemotherapy are active therapeutic options, but survival remains poor with no novel agents approved for the treatment of metastatic disease. Antibody-Drug Conjugate (ADC) targeting Nectin-4 and TROP-2 are dramatically changing the therapeutic landscape of Urothelial Carcinoma (UC). Given the biological and clinical similarities between CDC and UC, we evaluated Nectin-4 and TROP-2 expression in CDC.
Methods:
CDC tissue samples were collected from patients enrolled in the CICERONE study (NCT05372302), a multicentric trial that aims to define the transcriptomic profile of CDC with the goal of changing the paradigm of CDC management by using biology-driven treatments. Nectin-4 and TROP-2 are surface proteins involved in cell adhesion and proliferation. Their expression was assessed by immunohistochemistry (IHC) using a validated assay with a Nectin-4 antibody (clone M22-321b41.1) and a TROP-2 antibody (Ab227689 by Abcam).Staining area was quantified as a percentage (0–100%) and considered positive if >10% of the tumor surface was stained. Staining intensity was dichotomized into positive and weakly positive, based on a clear distinction from the negative control.
Results:
59 tissue samples from patients with diagnosis of CDC were considered eligible after centralized histological review. Fresh or archival tumor tissue was collected from either primary lesion or metastatic sites biopsies at baseline before the start of systemic therapy. Preliminary results demonstrated that Nectin-4 was expressed in 24 out of 59 samples (41%), while TROP-2 positivity was observed in 58/59 cases (98%).
Conclusions:
CDC appears to be a unique kidney tumor, which lies between UC and RCC clinically and biologically. Here we report for the first time the expression of two potential therapeutic targets in metastatic CDC, Nectin-4 and TROP-2, confirming the similarities between CDC and UC.Based on this encouraging data, along with the interesting results from EV-302 trial, we hypothesize that pembrolizumab in combination with Antibody-Drug Conjugate (ADC) could be active in mCDC and this combo will be assessed in the phase II RePRINT trial (NCT06302569). Clinical trial information:
NCT05372302
.
Use of integrated multi-omics profiling in renal cell carcinoma to identify molecular subtypes and associated clinical outcomes and therapeutic vulnerabilities.
Authors: Kim Chang Gon , Koo Harim , Kwon Woo Sun , Bae Woo Kyun , Hwang Eu Chang , Ham Won Sik , Hoon Cho Nam , Sa Jason , Park Jong Bae , Rha Sun Young
Published: February 2025

588

Background:
Although histologically defined subtypes exist, renal cell carcinoma (RCC) is a heterogenous disease, resulting in various treatment outcomes and prognosis. Here, we conducted comprehensive profiling of RCC with histopathologic, proteomic, phosphoproteomic, genomic, and transcriptomic analyses on tumor and paired adjacent normal tissues from 113 patients.
Methods:
Tumor and matched normal tissues were subjected to proteomic and phosphoproteomic analysis (N=113), whole exome sequencing (N=74), and whole transcriptomic sequencing (N=70).
Results:
RCC tumors are molecularly distinct from corresponding normal tissues, revealing the loss of tissue identity and de-differentiation. Various hallmarks of cancer were differentially observed at the individual patient level, highlighting the intertumoral heterogeneity of RCC. Proteomic subtyping classifies RCC tumors into four subtypes (C1-4) with distinct phosphoproteomic, genomic, and transcriptomic characteristics with prognostic and predictive implications. Among these subtypes, C1-3 were almost composed of clear cell RCC (ccRCC; 96.8%), whereas C4 was composed of non-clear cell RCC (nccRCC) or other types of cancer (100.0%). Among each subtype, C1 (N=37) exhibits the strongest angiogenesis signaling pathway activation with favorable prognosis after surgical resection. C2 (N=39) was characterized with enrichment in DNA repair pathways along with genetic alteration in
BAP1
(24.0%). C3 (N=19) was characterized by chromosome 7q amplification and associated with enrichment in inflammatory response with dismal prognosis along with therapeutic resistance to tyrosine kinase inhibitors and/or immunotherapy. C4 (N=18) was exclusively enriched with nccRCC with active mitochondrial and oxidation phosphorylation.
VHL
had significant
trans
-acting effects on various protein and phosphoprotein substrates, whereas
PBRM1
and
SETD2
had differential
cis
- and
trans
-acting profiles. Based on the
in silico
and
in vitro
exploration, we also identified CDK5, located on chromosome 7q and highly upregulated in C3 subtype, as a valuable target which can be modulated by small molecule inhibitors.
Conclusions:
This study reports a large-scale multi-omics-based approach of RCC, providing insights into biologic underpinning and evidence for rational treatment selection as well as linking the multiomics-derived phenotypes to clinical outcomes of RCC.
Impact of bleomycin shortage in patients with advanced testicular non-seminoma germ-cell tumors: A middle-income country cancer center experience.
Authors: Sobrevilla-Moreno Nora , Staufert-Gutiérrez Josette , Rodriguez-Bautista Ruben , Lopez Diego , Chamorro-Chamorro Jorge , Gonzalez Nuñez Carlos Arturo , Ramos-Ramirez Maritza , Cabrera Galeana Paula Anel , Jimenez Rios Miguel , Scavuzzo Anna
Published: February 2025

623

Background:
Standard of care for advanced NSGCTs is BEP (bleomycin, etoposide, cisplatin). Social, epidemiologic and economic factors can impact drug availability. In our institution, the COVID-19 pandemic limited accessibility to several antineoplastic drugs, including bleomycin. This analysis describes the frequency of BEP modifications and its impact in prognosis of intermediate (IP) and poor (PP) NSGCT treated at the National Cancer Institute in Mexico.
Methods:
Retrospective observational study performed from 2018 to 2022. Clinical characteristics and chemotherapy modifications were retrieved from electronic charts. Survival curves were built with Kaplan-Meier method and compared log-rank test to demonstrate effects of different clinicopathological variables on survival. Statistically significant variables in univariate analysis were included in multivariate Cox regression.
Results:
179 patients included. Median age 23 (16-56). 33% had IP and 66% PP; 32% had non-pulmonary visceral metastases (NPVM). 60% had at least one dose modification. Median dose of bleomycin was 67.5 IU (IQR, IU 0-90) per cycle. 42% of patients received the full-dose of bleomycin (Bleo360) dose. 55.8% of bleomycin modifications were due to drug shortage. 88% who received Bleo360 didn´t have other chemotherapy drug modifications (p<.001). Median Progression Free Survival (mPFS) was 17.4 months (95% Confidence Interval (CI), 11.8-23.1). Median Overall Survival (mOS) was 73.6 months (95% CI, 20.6-126.7). Univariate and multivariate analysis are described in the table.
Conclusions:
Oncology drug shortages may have serious consequences for patient’s survival. In our cohort the dose-modifications of bleomycin had a deleterious impact in the survival of IP/PP NSGCTs patients. Policy modifications and stakeholders awareness is paramount to decrease shortage of “vintage” oncological therapies.

Univariate and multivariate analysis.

Univariate
Multivariate

Variable

PFS HR(IC 95%)

p

OS HR(IC 95%)

p

PFS HR(IC 95%)

p

OS HR(IC 95%)

p

IPPP
0.34(0.21-0.56)
<0.0001
0.3(0.2-0.5)
0.0001
Ref.2.4(1.4-4.2)
0.002
Ref.2.8(1.5-5.5)
0.002

NPVMNoYes
0.53(0.36-0.78)
0.001
0.5(0.4- 0.9)
0.011
Ref.1.3(0.9-2)
0.2
Ref.1.1(0.7-1.9)
0.6

Bleo360YesNo
0.6(0.66-0.98)
0.04
0.63(0.39-1.0)
0.06
Ref.1.3(0.9-2.0)
0.1
Ref.1.3(0.8-2.1)
0.3

Log Tumor MarkerFavorableUnfavorable
0.51(0.30-0.84)
0.009

Ref.2.1(1.2-3.7)
0.008
Ref.1.6(0.9-2.9)
0.1
Clinical outcomes of stage IIA/IIB seminoma treated with radiotherapy and chemotherapy: Should regional therapy be considered the preferred treatment approach?
Authors: Glicksman Rachel , Jiang Di Maria , Bedard Philippe , Ye Xiang Y , Anson-Cartwright Lynn , Billfalk-Kelly Astrid , Krishna Satheesh , O'Malley Martin , Cheung Carol C , Shin Abigail , Hamilton Robert James , Warde Padraig , Chung Peter
Published: February 2025

629

Background:
With the publication of the Surgery in Early Metastatic Seminoma Trial there has been increasing interest in the use of regional therapy as first line treatment (reserving systemic therapy for relapse) in patients with testicular seminoma with low volume with retroperitoneal lymphadenopathy. Herein, we sought to evaluate outcomes with both management approaches.
Methods:
A prospectively maintained single-institutional database was retrospectively queried for patients diagnosed between 1995-2016 with de novo clinical stage IIA/B (CSIIA/B) or who relapsed on surveillance (Rel-CSIIA/B) treated with radiotherapy or chemotherapy. All patients were reviewed by the multidisciplinary team; while the preferred management policy during this period was radiotherapy, all treatment decisions were individualized at the physician/patient level.
Results:
The median follow-up was 7.1 years (IQR 4.3-9.9). There were 153 patients: 67 had de novo CSIIA/B (IIA-32, IIB-35) and 86 patients had Rel-CSIIA/B seminoma (IIA-51, IIB-35). One hundred and twenty patients (78%) received radiotherapy (IIA-78, IIB-42) and 33 (22%) received platinum-based chemotherapy (IIA-5, IIB-28). Eleven patients (IIA- 9/78, IIB- 2/42) relapsed following radiotherapy and 1 patient (IIB) relapsed following chemotherapy, corresponding to 5-year relapse rates of 10% for radiotherapy and 3% for chemotherapy. All 12 patients who relapsed were treated successfully with salvage chemotherapy.
Conclusions:
Regional therapy in patients with testicular seminoma with low volume with retroperitoneal lymphadenopathy gives excellent treatment results – recognising that a small proportion of patients will need salvage chemotherapy for cure, thereby exposing these patients to the morbidity of two treatment strategies. Our results support the view that regional therapy is a reasonable treatment option in this setting and should be discussed with all patients.
Clinical experience with EMACO chemotherapy in male choriocarcinoma: A single-center study.
Authors: Park Gwanhyun , Park Inkeun , Yoon Shinkyo , Lee Jae Lyun
Published: February 2025

640

Background:
Choriocarcinoma is an aggressive subtype of germ cell tumor that frequently metastasizes and progresses rapidly. In gestational trophoblastic tumors in females, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMACO) regimen is commonly used, but there are limited reports of its use in male choriocarcinoma. The purpose of this study was to retrospectively describe the clinical outcomes of the EMACO regimen in male patients with pathologically confirmed or clinically highly suspected choriocarcinoma at a single institution.
Methods:
We conducted a retrospective review of the medical records of male patients who received at least one cycle of EMACO chemotherapy between February 2013 and September 2023 at a tertiary hospital in Korea. We analyzed their baseline characteristics, tumor response, survival outcomes, and adverse events. Resection of residual tumors following EMACO chemotherapy was also considered part of the treatment process. The evaluation of tumor response was based on radiological examinations and changes in tumor markers.
Results:
In total, 15 patients were included in the study with a median age of 26 years. During diagnosis, 7 patients were found to have pure choriocarcinoma cell components on pathological examination, but all patients had elevated beta-hCG levels (median 177,000 mIU/mL, range 312–11,478,883 mIU/mL). At the time of EMACO administration, lung metastasis was the most frequent, observed in 12 patients, followed by brain metastasis in 7 patients. Seven patients received EMACO chemotherapy as 1
st
or 2
nd
-line treatment. The median number of chemotherapy cycles was 6. Tumor marker reduction or a decrease in tumor size was observed in 11 patients. Residual tumor resection was performed immediately after EMACO treatment in 7 patients, and no recurrence was observed in 6 patients during the follow-up period. Regarding Grade 3-4 toxicity, anemia was observed in 10 patients, thrombocytopenia in 6 patients, neutropenia in all patients, and elevated alanine aminotransferase levels in 6 patients. The median OS was not reached, with a median follow-up time of 24 months and a median PFS of 10.2 months.
Conclusions:
EMACO chemotherapy is an effective regimen for male germ cell tumors with pathologically confirmed choriocarcinoma components or markedly elevated hCG levels, and it may offer a curative treatment option when combined with resection of residual tumors.
Functional and oncological outcome of primary nerve sparing retroperitoneal lymph node dissection in marker negative testicular germ cell tumors in clinical stage IIA/B.
Authors: Heidenreich Julian , Heidenreich Axel
Published: February 2025

641

Background:
Guideline recommended treatment of choice for clinical stage IIA/B testicular nonseminomatous germ cell tumors (NSGCT) is the delivery of chemotherapy with 3 cycles PEB, 4 cycles PE. Despite its high curative efficacy, chemotherapy is associated with significant long-term toxicities. We evaluated the functional and oncological outcome of primary nerve sparing retroperitoneal lymph node dissection in marker negative NSGCT as a therapeutic option.
Methods:
Between 2018-2024 49 patients underwent primary RPLND for marker negative clinical stage IIA/B testicular germ cell tumors. All patients underwent nerve-sparing RPLND with a unilateral or bilateral template dissection. None of the patients received adjuvant chemotherapy. Follow-up was performed according to the EAU guidelines. The surgeries were performed by a single surgeon using an open transperitoneal approach.
Results:
The median age and median follow-up were 30.1 (17-35) years and 29.4 (11-47) months, respectively. The mean operative time, blood loss, and hospitalization duration were 131 (105-195) minutes, < 150ml, and 4.5 (3-9) days, respectively. 10 patients (9.18%) experienced a Clavien-Dindo grade 3a complication. Antegrade ejaculation was preserved in 90.8% of cases. On average, 21 (7-42) lymph nodes were dissected. 5 patients exhibited teratomatous elements in the primary orchiectomy specimens and 4 patients demonstrated teratomatous elements in the resected lymph nodes. The mean number of positive lymph nodes was 2 (1-3), with an average size of 1.3 (0.3-3.0) cm. Ten patients (20.4%) showed a pN0 stage. Six patients (12.2%) developed a recurrence and were cured by salvage chemotherapy.
Conclusions:
Primary RPLND for marker negative clinical stage II/ABnonseminomatous germ cell tumors results in a high cure rate without additional chemotherapy and it is associated with a low rate of complications if performed in experienced hands. Additionally, nsRPLND can safe unnecessary cytotoxic systemic therapy in 20% of patients. Furthermore, 8.1% of patients with teratoma containing lymph nodes would not have been cured by chemotherapy. Primary nsRPLND should be included in the management of marker negative CS IIA/B NSGCT.
Association between post-orchiectomy systemic inflammatory indexes and tumor characteristics in clinical stage I germ cell tumours.
Authors: Lesko Peter , Mego Michal
Published: February 2025

643

Background:
Approximately 25-30% of clinical stage I (CSI) GCT patients will experience disease relapse after orchiectomy. Adding adjuvant treatment will decrease relapse rate, however, on the contrary leads to over-treatment. Prognostic biomarkers such as lymph-vascular invasion (LVI) and/or embryonal carcinoma (EC) in non-seminoma (NSGCT) and rete testis invasion (RTI) and/or primary tumor size (PTS) in seminoma (SGCT) add limited value in treatment decision making. The aim of this study is to assess systemic inflammatory (SI) indexes and lactate-dehydrogenase (LDH) with clinico-pathological findings along with their prognostic impact.
Methods:
This is retrospective study, which included 159 diagnosed CSI GCT patients, who underwent active surveillance (AS) from June 2004 to November 2023. Medical records and pathology reports were collected retrospectively. Blood drawn must have been done less than 3 months since orchiectomy had been done. For survival analysis we used dichotomized values of studied biomarkers to “low” and “high” based on median value.
Results:
Median follow-up was 61 months (ranging from 1-230 months), with 2-years relapse free survival (RFS) 81.3% and 69.0% in SGCT and NSGCT respectively. We confirm inferior RFS among LVI presence compared to LVI absence in NSGCT ([HR]= 2.59, 95%CI (0.74-9.07), p=0.04). Trend to inferior RFS in NSGCT patients with EC predominance (≥50%) was observed as well ([HR]= 2.59, 95%CI (0.98-6.85), p=0.06). Prognostic impact of RTI and PTS(>4cm) in SGCT was not observed, p=0.24 and p=0.51, respectively. SI indexes were assessed among population, where higher neutrophil to lymphocyte ratio (NLR) value was associated with LVI presence and with advanced tumor stage in NSGCT. In SGCT, higher systemic inflammatory index (SII) level was associated with LVI presence as well as with advanced pathological stage. PTS (>4cm) was associated with higher LDH level among cohort of all studied patients, without significance among SGCT nor among NSGCT. Higher LDH value in NSGCT was also associated with EC predominance (≥50%).
Conclusions:
Our study for the first-time revealed associations of post-orchiectomy systemic inflammatory indexes and/or LDH in CSI GCT. Those new associations deserve further evaluation on larger cohort of CSI GCT to elucidate, whether, its associations in certain histology subgroups will improve stratification of risky population.
Circulating tumor DNA as a prognostic biomarker to predict retroperitoneal histology in patients undergoing retroperitoneal lymph node dissection.
Authors: Thakker Parth , Drake Connor , Zeng Jiping , Masterson Timothy A. , Cary Clint
Published: February 2025

646

Background:
Serum tumor markers (STM) are used in the management of patients with testicular cancer. However, a proportion have normal STM even with cancer present. Circulating tumor DNA (ctDNA) has shown promise in for detection of persistent disease. We sought to determine the utility of ctDNA for predicting retroperitoneal histology by comparing patients’ retroperitoneal lymph node dissection (RPLND) histology with their pre-operative ctDNA status.
Methods:
Patients undergoing primary (P-RPLND) or post-chemotherapy (PC-RPLND) from March 2023 to January 2024 had prospectively collected plasma ctDNA assay (Signatera, Natera Inc.) The association between ctDNA and RPLND histology was assessed. Sensitivity (SN), specificity (SP), and positive (PPV) and negative predictive values (NPV) were calculated for ctDNA to detect active cancer or teratoma alone in the RPLND histology.
Results:
Forty-six patients undergoing RPLND had pre-operative ctDNA collection with a median age of 33.5 (IQR:27-38.8). Plasma was collected on average, 8.6 days pre-operatively. Twenty (43.5%) patients underwent P-RPLND and 26 (56.5%) patients underwent PC-RPLND. ctDNA was positive in 23 (50%) patients. Two patients underwent P-RPLND for stage I disease and both had (-) ctDNA and histology. Eighteen patients underwent P-RPLND for stage II disease. Of these, 16 had active cancer, 1 had pure teratoma, and 1 had negative histology. ctDNA was positive in 15 of these patients all of which were found to have either teratoma or active cancer on pathology. Of the 3 patients with (-) ctDNA, 1 had negative histology, 1 had mixed, teratoma and seminoma, and 1 had pure seminoma. There were 26 patients who had ctDNA drawn prior to PC-RPLND. Of these, 4 had active cancer, 16 had pure teratoma, and 6 had necrosis on final RPLND histology. ctDNA was positive in 8 patients all of whom had either teratoma or active cancer on histology. Of the 18 PC-RPLND patients with a (-) ctDNA test, 1 had active cancer, 11 had teratoma, and 6 had necrosis. There were no false positive tests in the entire cohort. The SN, SP, PPV, and NPV were 85%, 77%, 74%, 87%, respectively for predicting active cancer. These numbers vary by primary or PC-RPLND patients (Table).
Conclusions:
To our knowledge, this is the first study evaluating test characteristics of ctDNA results in relation to RPLND histology. These findings suggest that ctDNA may be a useful adjunctive screening tool to predict active cancer or teratoma in the RP.

Test characteristics of ctDNA stratified by primary or post-chemotherapy RPLND.

Sensitivity
Specificity
PPV
NPV

P-RPLND

GCT and/or Teratoma
88%
100%
100%
60%

GCT only
88%
75%
93%
60%

Teratoma only
100%
26%
7%
100%

PC-RPLND

GCT and/or teratoma
40%
100%
100%
33%

GCT only
75%
77%
38%
94%

Teratoma only
31%
70%
63%
39%
Effectiveness and safety of RC48-ADC in combination with toripalimab as neoadjuvant treatment in HER2-positive muscular invasive urothelial bladder cancer patients.
Authors: Li Chenglong , Zhu Jiefu , Cheng Fan , Yu Weimin , Chen Zhiyuan , Song Chao , Zhu Hengcheng , Li Haoyong
Published: February 2025

710

Background:
Bladder cancer with high expression of human epidermal growth factor receptor 2 (HER2) is associated with pathological malignancy and poor prognosis. For patients with muscle-invasive bladder cancer that can be curative resected, the standard treatment is radical cystectomy and pelvic lymph node dissection following neoadjuvant chemotherapy (NAC). However, NAC is inefficient, and many patients cannot tolerate its adverse reactions. Therefore, a novel and safe strategy for these patients is needed after NAC.
Methods:
In this study, patients with muscle-invasive bladder cancer (MIBC) diagnosed with cT2a-4aN0M0 who were HER2 positive (HER2 IHC1+, 2+, or 3+) and intolerant to platinum underwent transurethral resection of bladder tumor (TURBT). This was followed by 4 cycles of toripalimab (200 mg, intravenous, D1, Q2W) combined with disitamab vedotin (2 mg/kg, intravenous, D1, Q2W) as neoadjuvant therapy. For patients who requested bladder preservation, we performed Re-cTURBT or multipoint biopsy to verify the status of residual tumors in the bladder. The primary endpoint was pathological complete response (pCR). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety.
Results:
A total of 28 patients were enrolled from April 2023 to Jun 2024 in our hospital. The median age was 68 years (range: 55-82). By the data cut-off in June 2024, 16 patients (57.1%) achieved clinical complete response (cCR). Among those who achieved cCR, the primary endpoint of pCR was 93.7% (15/16). The median follow-up time was 11.8 months. The median OS was not reached, ORR was 96.4% (27/28). Regarding safety, treatment-related adverse events (TRAEs) of any grade occurred in 21 patients (75%). The most common TRAEs were fatigue (68.3%), itching (57.5%), poor appetite (51.2%), alopecia (33.3%), and diarrhea (16.7%), all of which are grade 1-2. Grade 3 TRAE occurred in 4 patients (14.3%), with one patient experiencing cardiac tachycardia (3.5%) and 3 patients having hepatic dysfunction (10.7%). No grade 4 and 5 TRAEs were observed.
Conclusions:
Disitamab vedotin (RC48-ADC) combined with toripalimab as neoadjuvant treatment has shown excellent effectiveness and safety in curative resectable MIBC patients with HER2 positive. Those who achieved cCR and underwent Re-cTURBT and multipoint biopsy in bladder had an excellent pCR.
Hospitalizations in veterans treated with monotherapy vs combination therapy for metastatic hormone sensitive prostate cancer.
Authors: Ingram Kara , Wilson Robert , Doherty Jason M , Eaton Daniel B. , Schoen Martin W.
Published: February 2025

72

Background:
Current treatment of metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) monotherapy or combination therapy (ADT + docetaxel or an androgen receptor pathway inhibitor). However, no comparative studies have been conducted to assess the hospitalization rates and causes of admission between the two treatment groups. We assessed the hospitalization rates of the different therapies to determine adverse events and improve treatment selection in mHSPC.
Methods:
A nationwide retrospective study of 6,651 US Veterans with de novo mHSPC in the Veterans Health Administration between 2013-2021. Baseline characteristics for each treatment group were obtained including age, prostate serum antigen (PSA), total number of cardiac drugs, and total number of Anatomic Therapeutic Chemical (ATC) drugs. The five most frequent ICD codes associated with hospitalizations were obtained for each group, excluding the ICD codes for prostate cancer and bone metastases. Quasi-Poisson regression was used to determine differences in hospitalization rates between the two groups.
Results:
Evaluation of the median baseline characteristics between the two groups showed increased age and decreased PSA (Table). There was no difference between the number of cardiac drugs and total number of ATC drugs between the groups. The 5 most frequent ICD codes for monotherapy were AKI (17%), UTI (11%), essential hypertension (7%), sepsis (5%), and acute post-hemorrhagic anemia (4%). The 5 most frequent ICD codes for combination therapy were AKI (17%), UTI (13%), acute hypoxic respiratory failure (8%), sepsis (7%), and malnutrition (6%). The monotherapy group had a greater increase in hospitalization rates after therapy initiation when compared to combination therapy (
see table
). Quasi-Poisson regression for the hospitalization rates between the two groups had a p-value of 0.018.
Conclusions:
The rate of hospitalizations increased in the monotherapy treatment group compared to combination therapy. This is likely due to the monotherapy treatment group having a more advanced age and more severe comorbidities. Future directions could include comparing hospitalization rates of combination therapy with ARPI vs docetaxel. This analysis will guide physicians in selecting the more appropriate therapy according to a patient’s individual risk profile and co-morbidities.

Age (p < 0.001)
PSA(p = 0.008)
Pre-treatment hospitalization rate
Post-treatment hospitalization rate

ADT monotherapy(n = 5146)
75.0
76.2
120 per 1000 person-years
340 per 1000 person-years

ADT combination therapy (n = 1505)
72.0
86.3
100 per 1000 person-years
260 per 1000 person-years
Impact of relative dose intensity on efficacy of enfortumab vedotin monotherapy in platinum and ICI resistant metastatic urothelial carcinoma: A multi-institutional real-world analysis.
Authors: Endo Yuki , Kondo Yukihiro , Sakura Yuma , Kaneko Go , Hayakawa Nozomi , Ikarashi Daiki , Yamashita Ryo , Shirotake Suguru , Obara Wataru , Kikuchi Eiji
Published: February 2025

728

Background:
The treatment paradigm for metastatic or locally advanced urothelial carcinoma (mUC) has shifted towards combination therapies with Enfortumab Vedotin (EV) and Pembrolizumab. Understanding EV's characteristics is crucial for optimizing treatment. The EV-101 trial showed a correlation between exposure and efficacy, but few real-world studies explore how relative dose intensity (RDI) impacts outcomes. This study examines RDI's effect on efficacy using real-world data.
Methods:
We retrospectively analyzed 123 mUC patients treated with EV monotherapy as third-line or later, following progression after platinum-based chemotherapy and resistance to immune checkpoint inhibitors (ICIs). Data were collected from five institutions. We evaluated overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Patients were grouped into full dose on-schedule (FDO) and dose/schedule adjusted (DSA) based on EV dose and timing until best response (BR). On DSA group, relative dose intensity (RDI) until BR (BRRDI) was measured, and patients were classified into High (BRRDI > 80), Intermediate (80 ≥ BRRDI > 70), and Low (BRRDI ≤ 70) groups for comparison.
Results:
Among the 123 patients, median OS (mOS) was 14.8 Ms, median PFS (mPFS) was 7.1 Ms, and ORR was 48%, with a complete response (CR) rate of 9%. In the FDO group (31 patients), mOS was 9.3 Ms, mPFS was 4.5 Ms, and ORR was 29% (CR: 0%). In the DSA group (93 patients), mOS was 17.1 Ms (p=0.002), mPFS was 8.8 Ms (p=0.019), and ORR was 56% (CR: 12.1%) (p=0.0029 for ORR, p=0.017 for CR). In the BRRDI analysis, median time to BR was 2.6 Ms. ORR for High, Intermediate, and Low groups were 50% (CR: 20%), 58% (CR: 3.4%), and 63% (CR: 9.4%), respectively, with significant differences in CR (p=0.026).
Conclusions:
Patients requiring dose or schedule adjustments before best response showed better ORR, OS, and PFS than those on full dose. Higher BRRDI correlated with better CR, emphasizing the need to manage adverse events while maintaining dose intensity until BR.
Treatment patterns and clinical outcomes in patients with metastatic urothelial carcinoma in England: A retrospective observational study.
Authors: Shiri Tinevimbo , Nievaart Max , Gill Simran , Perkin William
Published: February 2025

740

Background:
In England, platinum-based chemotherapy with or without an immune checkpoint inhibitor is the standard-of-care for mUC patients. However, treatment patterns following first-line therapy remain unclear. There is a need to collect real-world data to enable an improved understanding of the clinical management of mUC in the National Health Service (NHS) and associated outcomes.
Methods:
This retrospective study obtained routine data for all patients diagnosed with mUC in England between January 2016 and December 2021 from the National Cancer Registration and Analysis Service (NCRAS). A treatment-based algorithm was developed to approximate progression to metastatic disease for those patients who had non-metastatic UC (Stage I-III). Variables collected include patient demographics, tumour characteristics, diagnostic tests, comorbidities, healthcare resource use, systemic anti-cancer therapy (SACT) and distributions of patients by lines of treatment. Kaplan-Meier methods were used to calculate overall survival (OS).
Results:
Of 61,816 patients diagnosed with UC between 2016 and 2021, 10,787 patients had mUC (stage IV (79.7%) at diagnosis or stage I-III (20.3%). The median age at diagnosis was 73.9 years, with 66.0% being male. Patients treated with anti-PD-L1 had a median age of 68.8 years. Only 36.5% (n = 3,942) received first-line therapy, with 24.3% (n = 959) reaching second-line therapy, while third-line therapy was delivered to 4.0% (n = 158) and fourth-line therapy to just 0.5% (n = 19) of patients with derived lines of therapy. The most common first-line regimen was ‘carboplatin + gemcitabine’ (n = 1,497; 38.0%), followed by ‘cisplatin + gemcitabine’ (n = 1,153; 29.2%). Pembrolizumab was the most common regimen administered at second line (n = 284; 29.6%) and remained the most common regimen at third line (n = 52; 32.9%). For the entire cohort, including patients that did not receive an active treatment, 12-month survival probability was 29.0%. The survival probabilities for patients treated at first-line, and reaching second-line and third-line, were 45.0%, 34.0%, and 30.0%, respectively. For the entire cohort, including patients that did not receive an active treatment, 12-month survival probability was 29.0%. The survival probabilities for patients treated at first-line, and reaching second-line and third-line, were 45.0%, 34.0%, and 30.0%, respectively.
Conclusions:
A high attrition rate in SACT was observed in mUC patients, and a poor prognosis indicated by a median OS of only 5.4 months from diagnosis. New treatment options particularly in the second-line setting could improve outcomes for patients. Further real-world studies are needed to evaluate their impact within routine clinical practice.
Evaluating the therapeutic role of lymph node dissection in variant histology bladder cancer.
Authors: Rahman Syed , Hesse David , Jalfon Michael , Kong Victoria , Ghali Fady
Published: February 2025

749

Background:
Outcome benefit associated with lymph node dissection (LND) at time of radical cystectomy have been suggested in urothelial bladder cancer (BC), but have not been evaluated in variant subtype BC. Our objective was to characterize the impact of LND on survival outcomes across variant subtype BC.
Methods:
The National Cancer Database was queried for cases of variant histology bladder cancers using International Classification of Disease-O-3 morphologic codes managed with radical cystectomy between 2004 and 2020. Cases were stratified by variant subtype and LND status. Primary outcome was overall survival associated pathologic nodal status and receipt of LND. Kaplan Meier analysis and Cox proportional hazards analysis were performed for survival analyses.
Results:
A total of 30,911 patients with variant UC histology were included in our analysis. that were managed with radical cystectomy. Rates for the no-LND group (pNx) were 33.1% in the micropapillary subtype, 42.2% in sarcomatoid, 68.4% in squamous, 48.9% in adenocarcinoma, and 56.2% in the neuroendocrine subtype. Median OS was higher in those that received a nodal dissection for squamous (91.3 [89.9, 92.7] vs. 62.8 [60.1, 65.6] months p<0.001) and adenocarcinoma (83.6 [73.1, 92.1] vs. 56.3 [43.5, 69.0] months p=0.020). On Cox proportional hazards regression, in T1/2 stage disease LN dissection was associated improved OS for sarcomatoid (0.50 [0.23-0.96] p=0.048), squamous (0.67 (0.61-0.76) p<0.001), adenocarcinoma (0.45 [0.23-0.85) p=0.015), and neuroendocrine (0.425 [0.21-0.85) p=0.017) variant histologies. In T3/4 disease, nodal dissection was statistically significant improved OS only for squamous histology (0.68 [0.59-0.77] p<0.001 and 0.70 [0.59-0.83] p<0.001 respectively). The survival benefit of LND appears to be attenuated following receipt of NAC across most histologic subtypes including micropapillary and sarcomatoid histologies.
Conclusions:
Our data highlights the varying degrees of therapeutic benefit across variant BC. LND particularly in sarcomatoid, neuroendocrine, and adenocarcinoma VHBC is correlated with improved survival, particularly in low clinical stages. The benefit also appears to be attenuated with receipt of NAC. These data help inform a variant subtype-informed surgical approach.