bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial biopsy results of the PATROL study: Prostate screening for people with inherited risk of developing aggressive prostate cancer.
Authors: Lee Daniel , Orr Caitlin , Maxwell Kara N. , Amini Andrew , Amling Christopher L. , Feng Aileen J , Goettl Stephanie , Follmer Kristin , Jun Grace , Holcomb Chenee , McCormick Shelley , O'Dea Margaret , Poole Maxwell , Rodgers Linda , Sokolova Alexandra , Tayeb Maliha N , Wolff Erika , Salari Keyan , Cheng Heather H. , Lin Daniel W.
Published: February 2025

426

Background:
Germline pathogenic variants (gPV) in prostate cancer (PrCa) risk genes are associated with aggressive disease and worse outcomes. However, the degree of risk by gene, the optimal PSA thresholds for biopsy, and the utility of MRI for screening are not well characterized. Therefore, we developed the PATROL study (clinicaltrials.gov: NCT04472338), a prospective multi-center early detection study for people at risk for PrCa due to variants in PrCa risk genes. Here, we report initial biopsy results of participants enrolled to date.
Methods:
The primary endpoint of PATROL is to determine the positive predictive value of predefined age-adjusted PSA thresholds and prostate-specific imaging for biopsy. Key eligibility criteria include: people ≥40y with prostates that carry a gPV in one or more of 13 PrCa risk genes. Participants undergo prostate biopsy per age-adjusted PSA threshold recommendations: PSA >1.0 ng/mL if <50y; PSA >1.5 ng/mL if 50-59y; PSA >2.0 ng/mL if ≥60y). Patients are encouraged to receive a prostate MRI at baseline and/or within one year of biopsy. Clinically significant prostate cancer (csPrCa) was defined as ≥Grade Group 2 (GG2).
Results:
Of 291 patients enrolled in PATROL at the time of this analysis, gPVs were most frequent in
BRCA2
(n=141, 48%) and
BRCA1
(n=71, 24%). 55 patients have undergone biopsy, with a median age of 57 (IQR 52-66) and median PSA of 2.2 (IQR 1.2-4.4) at time of biopsy. Of these biopsies, 10 (18.2%) had GG1 disease, and 11 (20%) had csPrCa. Of the men with csPrCa, six (55%) had PSA above the PATROL age-adjusted threshold but less than standard-of-care 4 ng/ml. An additional three (27%) patients had abnormal MRI with normal age-adjusted PSA. All 11 men with csPrCa underwent definitive treatment, while 7 of the men (70%) with GG1 initiated active surveillance. In a logistic regression model adjusting for age, gPV and PSA level, having a PIRADS 4 or 5 lesion was associated with csPrCa (OR 34.3, p=0.001).
Conclusions:
Screening gPV carriers using age-adjusted PSA and MRI resulted in 20% of biopsies detecting clinically significant prostate cancer. Conventional PSA thresholds for biopsy would have missed more than 80% of the clinically significant prostate cancer in men with gPV. Ongoing enrollment, site expansion and longer-term follow-up in this study, along with other studies will help improve the early detection of significant prostate cancer among men with gPV. Clinical trial information:
NCT04472338
.
Impact of PSMA-PET and conventional imaging on contemporary management in patients with biochemical recurrence after radical prostatectomy.
Authors: Ilano Arielle , Wang Lufan , Cowan Janet E , Washington Samuel L , Nguyen Hao , Cooperberg Matthew R. , Hope Thomas A. , Carroll Peter , Chu Carissa E
Published: February 2025

43

Background:
Prostate-specific membrane antigen (PSMA) PET imaging is recommended for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). This study describes the early clinical impact of PSMA-PET compared to conventional imaging (CT, MRI, or bone scintigraphy) in a contemporaneous period.
Methods:
This retrospective study includes patients with BCR after RP (defined as PSA≥0.2 after undetectable PSA post-operatively) who underwent PSMA-PET or conventional imaging (CI) between 2010-2023. The primary outcome was positive detection rate. The secondary outcomes were rates of salvage treatment (XRT±ADT) and second BCR. Cox proportional hazards modeling was used to predict risk of salvage treatment and second BCR.
Results:
217 post-RP patients were included. Of the 146 patients who underwent PSMA-PET and the 71 who underwent CI, 77 (52.7%) and 7 (9.9%) patients had positive imaging findings at a median PSA value of 0.23 (IQR 0.21-0.33) and 0.25 (IQR 0.25-0.44), respectively (p=0.36). 48 patients received both imaging modalities; 4 had positive results in both PSMA-PET and CI, while 26 were positive for PSMA-PET only, and 2 were positive on CI only. Patients underwent salvage therapy at lower median PSA values in the PSMA-PET group (0.40 vs 0.51, p<0.01). On unadjusted survival analysis, there were no differences in salvage therapy rates or second BCR rates between PSMA-PET or CI groups. On multivariable Cox proportional hazards modeling, year of PSA recurrence (HR 0.89, 95% CI 0.84-0.95), BMI (HR 1.45, 95% CI 1.02-2.07), ≥GG3 (HR 1.77 95% CI 1.3-2.4), and undetectable PSA≥6 months after RP (HR 0.50 95% CI 0.34-0.72) were associated with salvage treatment, but imaging modality was not. High genomic risk scores (Decipher>0.60) may be associated with second BCR (HR 2.03 95% CI 0.99-4.18, p=0.05) while other variables were not.
Conclusions:
PSMA-PET usage increased over the period of this study with higher sensitivity at lower median PSA at BCR. Imaging modality did not predict rates of salvage therapy or second BCR, while other clinical risk factors such as adverse pathology and high genomic risk score did. Analysis with a historical cohort is pending.
Chronic obstructive pulmonary disease mortality risk in renal cell carcinoma: A population-based study from 1992-2021.
Authors: Ogedegbe Oboseh John , Ntukidem Olanipekun Lanny , Bai Sakshi , Olafimihan Ayobami Gbenga , Egwom Peter , Malik Duresha
Published: February 2025

450

Background:
Renal Cell Carcinoma (RCC) is one of the most common malignancies in the United States, with about 82000 new cases and 15000 deaths each year. Over the years, RCC mortality rates have been on a downward trend, and this is attributable to cutting-edge research and treatment modalities; however, non-cancer deaths continue to have an increasing trend. Chronic Obstructive Pulmonary Disease (COPD) plays a significant role in this trend. We holistically evaluated the COPD mortality risk in patients with RCC.
Methods:
We utilized the Surveillance, Epidemiology, and End Results (SEER) database to retrieve cases of RCC with mortality secondary to COPD from 1992 to 2021. The histologic code for RCC in the SEER database is 8312/3, which is part of the International Classification of Diseases for Oncology, Third Edition (ICD-O-3). We then obtained the standardized mortality rates (SMR) and absolute excess risk (AER).
Results:
We compared the COPD mortality risk of each group to the general US population and noted significantly increased COPD SMRs. Patients with non-COPD causes of death and patients with unknown age, race and cancer stage were excluded. Regarding race, Non-Hispanic American Indians had the highest risk of COPD mortality (SMR 15.30, CI 3.16-44.71, AER 1029.25), followed by Non-Hispanic Asian/Pacific Islanders (SMR 8.67, CI 5.22-13.55, AER 1781.62), then Hispanics (SMR 3.67, CI 2.63-4.97 994.43), Non-Hispanic Whites (SMR 2.69, CI 2.44-2.95, AER 788.19), Non-Hispanic Blacks (SMR 2.33, CI 1.67-3.16, AER 648.94). Based on cancer stage, distant had the highest risk of COPD mortality (SMR 16.65, CI 9.70-26.65, AER 3985.35) while regional had relatively the lowest risk (SMR 3.62, CI 2.18-5.65, AER 1174.61) with localized (SMR 4.00 CI 3.37-4.72, AER 1572.98). In terms of age, patients aged 40-59 years had an SMR of 5.33 (CI 4.28-6.56, AER 619.66), 60-79 years had an SMR of 2.73 (CI 2.45-3.03, AER 838.76), while 80 years and above had an SMR of 2.00 (CI 1.63-2.43, p<0.05, AER 1261.89).
Conclusions:
We evaluated the extent of the risk of COPD-related deaths in RCC patients. Compared to the general United States population, patients with RCC have a higher risk of COPD mortality. Therefore, there is a need to improve primary and secondary preventive modalities and modify risk factors in this subset of patients to reduce morbidity and mortality.
Adherence to clinical surveillance guidelines in von Hippel-Lindau (vHL) disease: Evaluating the impact of a coordinated care centre implementation in Canada.
Authors: Born Dawson , Pasco Anna , Soleimani Maryam
Published: February 2025

460

Background:
VHL is a rare hereditary cancer syndrome, predisposing to the development of multiorgan tumour growth, including bilateral and recurrent clear cell renal cell carcinoma. While guidelines for the screening and management of these patients exist, adherence to guidelines is variable. The development of coordinated clinical care centres with multidisciplinary expertise in rare diseases has been demonstrated to improve outcomes.
Methods:
In this study, we reviewed adherence to surveillance guidelines prior to and after development of a Canadian provincial vHL clinic at our institution, British Columbia (BC) Cancer. Care in this clinic is provided both in-person and through telehealth. We sought to evaluate whether patient geographic distance from the clinic impacted time to being seen for consultation, and whether there was a change in management plan after being seen in the clinic.
Results:
Between June 2022, and April 2024, 57 patients were seen in the vHL clinic (median age 34, 58% female, and 42% male). Of these, 13 lived within 50km from the clinic, 7 within 50-100km, 8 within 100-500km, and 29 lived more than 500km away. We found significant improvement in adherence to nearly all surveillance guidelines after the development of the vHL Clinic (table). 10.5% of patients had never had germline confirmation of vHL and were referred for expedited testing after being seen. We did not find any difference in time from referral to consultation based on patient geographic proximity to the clinic, F(3,53)=1.10,
p
=0.35 nor the modality of initial consultation (t(55)=1.07,
p
=0.29; in person vs telehealth). Finally, after initial consultation, 87% of patients had a change in their management plans, most commonly involving referral for further subspecialty evaluation (n=41) or initiation of pharmaceutical treatment (n=24).
Conclusions:
Our results add to existing evidence that coordinated care centres with multidisciplinary expertise in vHL are feasible in the Canadian public healthcare system and can result in improvements in quality of care. Our clinic model has a robust multidisciplinary care team that utilizes technology to reach patients for equitable access to care. Future work will evaluate potential cost savings to the healthcare system with this model, as well as patient satisfaction with their care pre and post participation in the vHL clinic.

Adherence to clinical screening guidelines for patients with vHL before and after consultation with the BC cancer provincial vHL clinic.

Screening Guideline Parameter
Pre connection with vHL clinic
Post connection with vHL clinic

Central nervous system imaging
51.8%
100%*

Abdomen/Pelvis imaging
44.6%
100%*

Metanephrines
8.9%
64.3%*

Ophthalmologic
75.0%
85.7%

Audiology
21.4%
85.7%*

*Statistically significant difference (
p
<0.05).
Understanding health inequalities based on socio-economic factors and geographical location in renal cell carcinoma: A large-scale national cohort study in England.
Authors: Das Prantik , Owide Joshua , Mohammed Rania
Published: February 2025

464

Background:
Kidney cancer is 7
th
most common cancer in England with renal cell carcinoma (RCC) accounting for about 80% of all cases of kidney cancer. It has well established that the incidence and mortality rates of RCC are strongly associated with four main risk factors, including family history, lifestyle, environment, and occupation. In addition, unequal access to improvements in RCC cancer treatment and limited access to screening and diagnosis, significantly contribute to the difference observed in survival rate.
Methods:
We aim to assess the association between area-level measures of socioeconomic deprivation, from the 20% most deprived of the population (quintile 1) to the 20% least deprived (quintile 5), or geographical regions in England, with both the diagnosis and treatment of RCC, over five years from April 2019 to March 2024. This study utilized patient-level data for primary and metastatic renal cancer (ICD-10: C64) by organisation, procedure, ethnicity, age group and deprivation quintile from Hospital Episode Statistics (HES).
Results:
Among 54,535 included patients, 9,935 (18.2%) came from the most deprived quintile and 11,330 (20.8%) from the least deprived quintile with a mean age of 62 years across all patients. Of included patients, 43,290 (79.3%) were Caucasian (white) and the remaining 14,235 patients came from other ethnic groups. In total, 61.0% of patients were middle aged (aged from 45 to 74), with 35.0% elderly (75 and above) and 5.4% classed as young (below 45). Caucasian populations have higher rates of metastatic disease (34.6%) vs non white (29.6%). Prevalence of metastatic disease increases with age (24.1% vs 33.3% vs 34.6% in young, middle aged and elderly respectively). Higher deprivation is associated with lower rates of nephrectomy (42.3% in most deprived vs 43.6% in least deprived). Patients in areas of higher deprivation are on average younger than those in least deprived areas (57 years in most deprived vs 64 in least deprived) while non-white renal cancer patients are also typically younger (57 non-white vs 64 white). The Midlands (central England) region is associated with the highest rates of metastatic cancer (37.4%) while North East & Yorkshire (30.8%) and London (31.1%) has the lowest metastatic disease rates. Conversely, total nephrectomy rates are highest in North East & Yorkshire while they are lowest in the South West region and London (46.6% vs 42.8% vs 43.0% respectively).
Conclusions:
This study presents the most recent and extensive RCC data from England, exploring the impact of socioeconomic status and geographical location in diagnosis and management of RCC. These findings could facilitate targeted initiatives to improve health inequity across regions in England.
Burden of cancer in metastatic renal cell carcinoma (mRCC).
Authors: Battle Dena , Griffith Meghan , Msaouel Pavlos , Psutka Sarah P. , Vaishampayan Ulka N. , Zhang Tian , Staehler Michael D.
Published: February 2025

467

Background:
Combination regimens and sequencing of multiple agents have significantly improved clinical outcomes for patients (pts.) with mRCC. We sought to assess the burden of mRCC on patients and interference with daily life.
Methods:
The survey was developed by the Kidney Cancer Research Alliance (KCCure), and broadcast between 09/24 and 10/24 to pts. via website, mailing lists and social media platforms.
Results:
Of 1167 respondents, 492 pts. had received systemic therapy for mRCC. Median age was 58.7 years (range 17.2 - 87.0), 83% were from the United States. 42% were on first line treatment, 30% second line, 13% third line, and 15% in fourth or later line. 69% were on systemic on therapy with evidence of disease, 10% were receiving treatment with no evidence of disease, 13% had discontinued treatment with no evidence of disease; 8% had discontinued treatment with evidence of metastatic disease. 45% of pts. take ≥7 prescriptions per day, 11% take ≥10 prescription medications per day. One-third (33%) of pts. are concerned they are taking too many medications. In the last year, pts reported seeing 4.24 (range 1-17) different types of doctors for cancer related care. In the last 90 days: 36% have gone to the emergency room, 20% more than once. 96% had blood drawn at least once, 35% had ≥5 blood draws. 95% had at least one clinic visit, 22% ≥5 clinic visits. 30% had ≥5 pharmacy visits. 23% have been hospitalized, 12% for ≥5 days. In the last year, 45% were hospitalized at least once, 52% more than once, 11% ≥5 times. Hospitalizations and visits to the emergency room were significantly correlated with a lower quality of life and higher NCCN distress score (p<.001). 89% of pts think about cancer every day; 44% spend a few to several hours per day thinking about cancer. When asked how confident they feel about making plans, 33% feel completely confident making plans 6 months from now, 21% one year and 10% two years from now. Pts. with no evidence of disease are significantly more likely to rank their QOL as excellent (19%) compared to pts. with evidence of disease (4%), independent of treatment. Pts. who have discontinued treatment and still have evidence of disease rank their QOL as poor (17%).
Conclusions:
Pts. living with mRCC are physically and mentally consumed with cancer and disease management. mRCC disrupts fundamental daily activities, including eating, sleeping, and socializing. Pts. must routinely engage with the healthcare system, extensively managing scheduled and unscheduled appointments with multiple providers. Nearly all contemplate their cancer daily. More research is needed to improve care and alleviate disease burden in mRCC.

Disruption of daily and routine activities.

Activities Impacted by Cancer
Frequency - Always or Often

Eating a meal
37%

Sleeping
38%

Engaging with Friends
31%

Grocery Shopping
25%

Attending an Event
31%

Buying Clothes
18%

Traveling
43%
Extensive necrosis as a prognostic indicator in metastatic RCC patients undergoing deferred cytoreductive nephrectomy after immunologic checkpoint inhibitor treatment.
Authors: Siqueira do Amaral Paulo , Beckermann Katy , Polho Gabriel Berlingieri , Moses Kelvin A. , Gordetsky Jennifer B. , Chang Sam S. , Luckenbaugh Amy , Ancell Kristin Kathleen , Lambrecht Morgan , Schaffer Kerry Roe , Kaiser Elizabeth , Joyce Daniel D. , Rini Brian I.
Published: February 2025

468

Background:
The role of cytoreductive nephrectomy (CN) in patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitor (ICI)-based therapies remains under debate. Retrospective cohorts have reported shrinkage in the primary tumors and no residual tumor in primary specimens (pT0), however, the clinical relevance has not been explored. Assessing the pathological outcomes of CN following ICI may provide valuable information.
Methods:
This is a single-center retrospective analysis of metastatic/locally advanced RCC who underwent CN between May 2017 and September 2024 after ICI-based treatment. Demographic and clinicopathological were collected. The primary endpoint was the rate of patients with extensive necrosis (EN), defined as ≥ 95% of necrosis in the resected primary tumor. Progression-free survival (PFS) was calculated at two timepoints: from the date of ICI initiation (PFS1) and from the date of surgery (PFS2) until event (progression or death) or last follow-up, using the Kaplan-Meier method. Differences between groups (pts with EN in resected kidney vs not) were assed with the log-rank test and hazard ratios were calculated with Cox regression model. Correlations were made with the Fisher test between presence of EN and other categorical variables.
Results:
Twenty-five pts were identified, with a median age of 62 years (range, 40–83), and median follow-up of 31.5 months after initiating ICI. 84% were metastatic, with 84% receiving first-line ICI-based combinations (5 Ipi/Nivo;16 ICI-TKI), while the remaining 16% had second-line nivolumab. The median ICI exposure before surgery was 10.5 m (range, 2.1–42.7) in the entire cohort, 12.7 m (range, 2.1–28.8) in the EN subgroup and 10.3 m (range, 3.1–42.7) in the non-EN. Best overall radiological response prior to surgery included 4% CR, 68% PR and 28% SD. Pathological assessment revealed 76% clear cell, 16% unclassified and 8% papillary RCC and 16% had a sarcomatoid component. 40% of pts had ≥ 95 % necrosis, with half of these pts (20%) achieving pT0. The median PFS1 was numerically longer in pts with EN, not reached (NR) vs 27.7 m, (HR 0.33; 95% CI, 0.09 -1.26; p = 0.09). The median follow-up after surgery was 10 months, and the median PFS2 was longer in the EN subgroup, NR vs 9.7 m, (HR 0.2; 95% CI, 0.04–0.96; p < 0.05). No significant correlations were found between EN and Fuhrman grade, presence of sarcomatoid differentiation, treatment duration, or radiological response.
Conclusions:
ICI-based regimens showed activity in primary RCC tumors, leading to EN (≥ 95% of necrosis) in a subset of pts. Those who achieved EN appear to have reduced risk of disease progression.
Exploring the efficacy of belzutifan in the treatment of renal cell carcinoma associated with von Hippel-Lindau disease: A comparative analysis with external control arm.
Authors: Linehan W Marston , Jemielita Thomas , Cornell Jerry , Chen Ke , Ball Mark Wayne , Srinivasan Ramaprasad , Liu Yanfang , Perini Rodolfo F. , Pinto Cathy Anne
Published: February 2025

469

Background:
Randomized controlled trials are the gold standard for demonstrating treatment efficacy but are not feasible in certain disease settings. In such cases, external control arm (ECA) analysis can be an effective way to interpret experimental treatment results. Our aim, based on a natural history study (NHS), was to develop an ECA for a Phase 2 single-arm trial (LITESPARK [LS]-004) for belzutifan in 61 patients with VHL disease-associated RCC. With a median follow-up of 37.8 months in LS-004, the objective response rate (ORR) for VHL RCC patients was 64% (95%CI: 50.6, 75.8) and the median time to surgery (TTS) was not reached.
Methods:
The ECA was developed using NHS data for VHL RCC patients undergoing active surveillance at the US National Cancer Institute with up to 5 years of follow-up. Key LS-004 eligibility criteria (e.g., no prior systemic therapy or metastasis) were applied. Propensity score (PS) weighting was used to balance baseline characteristics (age, sex, number and size of RCC, prior surgery and time from prior surgery, VHL mutation status) between LS-004 and ECA, with balance evaluated using standardized mean difference (SMD). PS adjusted point estimates and 95% CI for ORR, assessed by independent blinded committee review using RECIST 1.1, and TTS were estimated. For the ECA, the ORR was evaluated among patients with ≥3 serial scans to allow the opportunity for a confirmed response.
Results:
The ECA included 244 patients with 178 patients in the ORR analysis. Prognostic factors were well balanced between the ECA and LS-004 with a SMD<0.1 for all covariates. The PS adjusted ORR (95% CI) for LS-004 and the ECA was 63.9% (51.9, 76.0) and 1.5% (0.0, 3.3), respectively. Median (95% CI) TTS was 44.4 (35.7, 51.1) months in the ECA, and not yet reached in LS-004.
Conclusions:
The magnitude of the treatment effect with belzutifan is large compared with the ECA. Although residual confounding is still possible, including effects of unmeasured confounders, observing such a large effect is unlikely due to chance. The results support the demonstrated antitumor activity and efficacy of belzutifan in the treatment of VHL RCC.
Barriers to and facilitators of first-line treatment intensification (TI) in metastatic castration-sensitive prostate cancer (mCSPC) by practice setting and intensification frequency: A sub-analysis of IMPLEMENT.
Authors: Agarwal Neeraj , Loeb Stacy , El-Chaar Nader N. , de Ruiter Laura , Kim Janet , Mack Jessica , Thompson Betty , Rich-Zendel Sarah , Sheldon Jay , Joo Jin Su , Dyson Judith
Published: February 2025

48

Background:
First-line TI (i.e., androgen-deprivation therapy + chemotherapy, androgen receptor pathway inhibitors, or both) is recommended for mCSPC but is underutilized. Phase 1 of IMPLEMENT identified barriers to and facilitators of TI. Phase 2 prioritized these factors and identified resources to increase TI. This sub-analysis describes the results in academic and nonacademic settings, and among high and low intensifiers (physicians who use first-line TI in >50% vs ≤50% of patients, respectively).
Methods:
Phase 1: Semi-structured virtual interviews with 18 oncologists and 18 urologists, using an implementation science approach based on the Theoretical Domains Framework to analyze themes by setting and intensification frequency. Phase 2: Discrete choice experiment with 302 physicians who reviewed descriptions of potential resources across 12 scenarios and selected the most helpful for increasing TI. We used a mixed-effects logistic regression model to calculate a coefficient of helpfulness for each resource to identify those with the strongest impact on TI decisions.
Results:
Phase 1:Low intensifiers and nonacademic physicians more frequently reported barriers to TI. Low intensifiers had gaps in clinical trial knowledge, tended to reserve TI for later, and had low-intensifier peers; nonacademic physicians had concerns about side effects, cost, and impact on quality of life. High intensifiers and academic physicians more frequently reported facilitators such as good clinical support and anticipated regret about missing the best chance at improving survival. Phase 2: Significant differences were noted between high and low intensifiers in the utility of decision support and clinical trial summaries (Table).
Conclusions:
Decision support tools and databases of post-treatment options may help address barriers to TI and improve guideline-concordant care.

Resource, mean COH (±SD)
Academicn = 81
Nonacademicn = 221
High intensifiersn = 184
Low intensifiersn = 118

Database of post-treatment options
1.89(0.38)
1.80(0.38)
1.94(0.39)
1.65(0.36)

Decision support tool linking patient characteristics to first-line treatment options
1.60(0.53)
1.75(0.53)
1.45*(0.52)
2.12*(0.51)

Summaries of key clinical trial data
1.39(0.40)
1.25(0.44)
1.55*(0.44)
0.88*(0.37)

Cross-specialty treatment guidelines
0.57(0.26)
0.59(0.25)
0.48(0.22)
0.75(0.30)

Information comparing clinical outcomes of first-line vs later TI
0.41(0.21)
0.37(0.18)
0.40(0.19)
0.36(0.19)

Tools to reduce administrative burden
0.13(0.06)
0.23(0.11)
0.18(0.10)
0.25(0.11)

COH, coefficient of helpfulness (scaled to have average value of 1, i.e., >1: above average utility; <1: below average utility).

*
P
< 0.05 from bootstrap testing of subgroup averages.
Real-world analysis of pembrolizumab utilization and characteristics of patients being prescribed treatment in early stage RCC.
Authors: Uzzo Robert , Bhattacharya Rituparna , Bupathi Manojkumar , Elfiky Aymen , Monnette Alisha , Todoroff Karen , Conkling Paul R. , Sundaram Murali
Published: February 2025

480

Background:
In the United States, adjuvant pembrolizumab was approved on November 17, 2021, for patients with RCC with intermediate-high (T2N0M0-G4, T3N0M0, any grade) or high risk (T4, any grade; N+, any T, any grade; and M1NED patients) of recurrence following nephrectomy. This study aims to assess adoption of adjuvant pembrolizumab in routine practice and demographic and clinical characteristics of post nephrectomy RCC patients who received this therapy.
Methods:
This retrospective study included adult patients with non-metastatic localized RCC who underwent nephrectomy between November 17, 2021, and December 31, 2022, and were seen in the U.S. Oncology Network. Patients were excluded if they were treated for other documented primary cancer diagnoses or enrolled in clinical trials. Descriptive analyses were conducted to evaluate demographic, clinical, and treatment characteristics overall, and for patients who received adjuvant pembrolizumab monotherapy and those who did not. Multivariate logistic regression was used to identify factors associated with adjuvant pembrolizumab use.
Results:
In total, 178 patients were included. The mean age was 62 years (SD 11.8), with a majority being male (66.3%, n=118), and a median follow-up of 7.9 months (Q1,Q3: 4.1,9.8). The majority had intermediate-high risk (n=86, 57.5%), clear cell (cc) RCC (n=147, 82.6%) and received adjuvant pembrolizumab monotherapy (n=118, 66.3%). Among those who received adjuvant pembrolizumab, 90.7% had ccRCC, 62.5% were intermediate-high risk (T2N0G4: 8 (55.1%), T3N0 All Grades: 53 (44.9%)), 27.5% were N+ with a median follow-up of 8.3 (Q1, Q3: 6.0, 10.1) months. Median time to the start of adjuvant pembrolizumab post nephrectomy was 1.6 months (Q1, Q3: 1.3,2.1). The median time to treatment discontinuation was 11.5 months (Q1, Q3: 9.0, 11.5) (the recommended duration of treatment for adjuvant pembrolizumab is: 12 months at 17 cycles at 200mg/ Q3W or 9 cycles at 400mg/Q6W). Multivariate analysis showed that patients with non ccRCC histology were 93% less likely (p-value: <0.0001) and those whose with first oncologist visit >=2 months post nephrectomy were 60% less likely (p-value:0.035) to receive adjuvant pembrolizumab treatment.
Conclusions:
This study demonstrated notable uptake of adjuvant pembrolizumab among post-nephrectomy RCC patients in this community setting following FDA approval. RCC histology and the timing of oncologist visits post nephrectomy were significant factors influencing the receipt of adjuvant pembrolizumab. Future research should focus on examining referral patterns, and identifying the drivers and barriers to treatment adoption, with the goal of developing strategies to enhance its integration. Additionally, future research may explore long-term outcomes and real-world effectiveness of adjuvant pembrolizumab.
A multi-centre review of the use of adjuvant pembrolizumab for renal cell carcinoma.
Authors: McCarthy Eleanor , Chadwick Alice , Soto-Castillo Juan Jose , Pickering Lisa M , Frazer Ricky Dylan , Pillai Manon , Waddell Tom , Lindsay Duncan , Agarwal Ansh , Matthews Diana , Khalid Mahrukh , Grumett Simon Aird , Adamson Ellis , McGrane John , Dearden Helen Clare , Vasudev Naveen , Charnley Natalie
Published: February 2025

484

Background:
In patients with increased risk of recurrence after surgical resection of renal cell carcinoma (RCC), adjuvant treatment with pembrolizumab has been shown to reduce recurrences and improve overall survival. This treatment is now offered as standard of care in England. In the KEYNOTE 564 trial 96.3% of patients who received pembrolizumab experienced at least one adverse event and 32.4% of patients experienced an adverse event of grade 3-5. 38.9% of trial patients discontinued treatment early; 21.3% due to adverse events and 10.5% due to disease recurrence. 7.4% of patients who were treated with pembrolizumab were treated with high dose systemic steroids (≥40mg prednisolone per day). Aims: To evaluate how real world data compares to the findings of KEYNOTE 564, in UK centres.
Methods:
This was a retrospective review of 182 patients treated with adjuvant pembrolizumab following surgery for RCC across 7 centres in the UK between 2022-2024. Toxicity, discontinuation, use of steroids, and recurrences were assessed.
Results:
182 patients were started on adjuvant pembrolizumabbetween 2022-2024. Median FU is 8.4 months. Overall, 18 patients (9.9%) have experienced recurrence, and 15 (83.3%) of these occurred during treatment. 82 (45.1%) patients are currently undergoing treatment, and 41 (22.5%) patients completed the full 12-month course. 59 (32.4%) patients did not complete the full course, 44 (24.1%) due to toxicity and 15 (8.2%) due to recurrence. Mean number of cycles completed for patients discontinuing treatment was 3.4 (range 1 – 8). Toxicity was varied with endocrine (24%), skin (23%) & colitis (12%) being the most common toxicities of all grades. 24 (13.2%) and 3 (1.6%) patients experienced grade 3 and grade 4 toxicities respectively. The commonest toxicity leading to treatment discontinuation was colitis (27.3%). The number of patients requiring steroids for toxicity management was 59 (32.4%) with 34 (18.6%) requiring high dose steroids and 7 (3.8%) requiring additional immunosuppressive agents (methotrexate (3), infliximab (3) and MMF (1)). 26 (14.2%) patients required hospitalisation for management of toxicity. There was 1 treatment-related death due to complications from colitis and nephritis.
Conclusions:
In our group of patients, discontinuations of Pembrolizumab due to toxicity and recurrence rates were similar to data from KEYNOTE 564. A larger proportion of patients in our real world data were treated with high dose steroids (19%) compared to the trial (7.4%).
Trends in kidney cancer: Exploring the impact of sex and age on stage of disease, and prognosis during the past three decades in Denmark—A DaRenCa study.
Authors: Ahrenfeldt Johanne , Jespersen Jesper Huitfeld , Tønder Jens Ejrnæs , Iisager Laura , Krarup Keller Anna , Fristrup Niels , Laurberg Tinne , Lyskjær Iben
Published: February 2025

485

Background:
Over the past 30 years, renal cell carcinoma (RCC) management has undergone significant advancements, driven by increased diagnosis through imaging scans and the development of more effective systemic therapies for metastatic disease. Understanding the impact of early detection and evolving treatment strategies on patient outcomes is crucial for guiding future advancements in RCC care. This nationwide registry-based cohort study investigates how the number of RCC cases, stage at diagnosis, and prognosis have changed during the past 30 years in Denmark, and how these are associated with sex and age.
Methods:
A population-based cohort was established, including all Danish patients aged 18 and older diagnosed with RCC from 1992 to 2021, excluding individuals with a prior cancer history. Patients were identified and followed from the date of diagnosis until death or end of follow-up using nationwide register data. Comorbidities prior to RCC diagnosis were assessed using nationwide hospital admittance records.
Results:
A total of 17,423 RCC patients were diagnosed during the past 30 years in Denmark. The male-to-female ratio changed significantly from 0.59:0.41 in 1992-1996 to 0.72:0.28 in 2017-2021 (P < 0.001). The age distribution of patients at diagnosis remained relatively constant (ranging from 65-67 years). The number of RCC cases increased from 2,244 in 1992-1996 to 3,947 in 2017-2021. We observed stage migration over time, with Stage I cases increasing from 30% in 2002-2006 to 55% in 2017-2021, and Stage IV cases decreasing from 45% in 2002-2006 to 20% in 2017-2021, while the absolute number of metastatic cases remained relatively unchanged. The median survival of patients with metastatic disease steadily increased by 314% from 4.1 months in 1992-1996 to 12.9 months in 2017-2021. Additionally, married patients showed better survival than divorced and unmarried patients.
Conclusions:
During the past 30 years, the number of RCC cases in Denmark has increased, primarily driven by early-stage tumors, while the number of metastatic cases has remained stable. Additionally, the proportion of female patients has decreased across all stages of RCC during the observation period. Overall survival has significantly improved over time, highlighting the impact of early detection and treatment advancements. Despite only studying Danish patients, this study serves as a reference for how patient dynamics have evolved with the advancements in the diagnosis and treatment of RCC.
Characterization, treatment and survival outcomes of penile cancer: Over a decade in a tertiary Mexican center.
Authors: Cervin Cristhel , Saenz Aaron , Perez Rosado Mariana , Diaz Alvarado Maria Guadalupe , Perez Perla , Aguirre Jorge , Madrid Morales Mariana
Published: February 2025

5

Background:
Penile cancer, as a rare disease worldwide, represents 4.1% of urological cancers in Mexico. Despite the need for multimodal treatments, delayed diagnoses and poor follow-up adherence impact survival outcomes. This study aims to characterize the patient population diagnosed with penile cancer at a tertiary center in Mexico and evaluate treatment and survival outcomes.
Methods:
This cross-sectional retrospective cohort study analyzed patients diagnosed with penile cancer at the medical oncology and urology services of Centro Médico Nacional 20 de Noviembre from January 2005 to January 2024. Statistical analyses included Kaplan-Meier survival analysis and subgroup analyses by age, surgical treatment type and radiotherapy.
Results:
Of the 54 patients analyzed, the median age was 64 years (34-84) with a median time symptoms to diagnosis of 12 months. Clinical stages at diagnosis were stage I (9.2%), II (40.7%), III (29.6%) and IV (20.3%). Human papillomavirus (HPV) was positive in 17 patients (31.4%), negative in 2 (3.7%) and undetermined in 35 (64.8%). HIV status was undetermined in 88.8% of cases. Additionally, 22 patients (40.7%) were smokers. Tumor anatomical locations were glans (64.8%), prepuce (25.9%), body of the penis (7.4%) and scrotum (1.8%). Histologically, all cases were squamous cell carcinoma. Most common sites of metastasis were lymph nodes (79.6%), lungs (7.4%) and liver (5.5%). Systemic therapy was administered to 38.8% and radiotherapy to 55.5% with a median overall survival of 44.8 months. Surgical treatment was required in most cases (88.8%), with total penectomy and bilateral inguinal dissection predominating in 21 patients (38.9%), followed by total penectomy alone in 8 (14.8%), partial penectomy with bilateral inguinal dissection in 6 (11.1%) and partial penectomy in 8 (14.8%). Tumor resection alone was performed in 5 (9%). Subgroup analysis based on age, surgical technique and radiotherapy indicated that overall survival was not significantly affected by age when comparing patients <60 years to those >60 years (p=0.1). However, patients undergoing partial penectomy had significantly higher survival rates (12 months vs 7 months; p=0.04), regardless of clinical stage. There was no significant difference in overall survival between patients who received radiotherapy and those who did not (p=0.7).
Conclusions:
Despite advanced stage at diagnosis, the results suggest that surgical intervention is associated with improved survival rates. However, neither age nor radiotherapy significantly impacted overall survival outcomes, likely due to the homogeneity of clinical stages and surgical approaches. These findings underscore the importance of early detection and comprehensive management strategies to improve survival in this patients.
Efficacy of targeted therapies (TT) after HIF-2⍺ inhibitor-based treatment in advanced renal cell carcinoma (aRCC).
Authors: Rioja Patricia , Rey-Cárdenas Macarena , Esteban Villarrubia Jorge , Plata David , Sparagna Ileana , Schutz Fabio A. B. , Manneh Ray , Iacovelli Roberto , Flippot Ronan , Castellano Daniel , de Velasco Guillermo
Published: February 2025

508

Background:
Hypoxia-inducible factor 2⍺ (HIF) inhibitors are active in renal cell carcinoma refractory to prior treatment with tyrosine kinase inhibitors (TKI) and immunotherapy, including anti-PD-1 monotherapy or combinations with anti-CTLA-4, and represent a new therapeutic option. However, the efficacy of TT after HIF-2⍺ inhibitors has not been assessed.
Methods:
A retrospective review of medical records from aRCC patients (pts) treated with HIF-2a inhibitors at five academic institutions was conducted. Pts who received subsequent treatment with TT were identified to collect outcomes in terms of best radiological response by RECIST 1.1 criteria (BRR), time to treatment failure (TTF), defined as treatment failure can be defined as one or a combination of events, including disease progression, discontinuation of treatment due to toxicity, or death from any cause; and overall survival (OS). This work was approved by an ethics board and all patients provided approval.
Results:
Data of 35 pts were available: 30 (85%) were male and 18 (51%) were metastatic at diagnosis. IMDC risk group was favorable, intermediate and poor in 11 (31%), 20 (57%) and 4 (11%) pts, respectively. Belzutifan was administered as monotherapy in 27 (77%) and in combination in 8 (22%) pts. Regarding first subsequent TT, 30 (85%) received TKI and 5 (14%) received mammalian target of rapamycin (mTOR). TT post HIF-2a was administered as second-line, third-line, fourth-line and beyond fourth-line in 3 (8%), 4 (9%), 18 (51%) and 10 (28%) pts, respectively. Treatment was interrupted due to progression in 28 (80%), 1 (3%) discontinued due to toxicity and 7 (20%) remained on treatment after data cut-off. Median follow-up was was 19 months.Median TTF on subsequent TT was 5.74 months (95% CI: 2.82–8.00). Median OS was 10,49 months (95% CI: 6,13-NR) with 17% pts alive at 1 year from the initiation of subsequent TT. Investigator-assessed BRR to subsequent TT was available for 33 out of 35 pts. Partial response and stable disease were observed in 7 (20%) and 12 (34%), respectively. Progressive disease was observed in 14 (40%) pts.
Conclusions:
Both VEGF/VEGFR and mTOR inhibitors have activity following HIF-2α blockade. However, 40% of patients will be refractory to treatment. This highlights the need for new drugs with distinct mechanisms of action.
Comorbidity burden and effectiveness of immunotherapy in patients with metastatic renal cell carcinoma.
Authors: Yekeduz Emre , Zarba Martin , Saad Eddy , Wells Connor , Machaalani Marc , El Hajj Chehade Razane , Eid Marc , Labaki Chris , Nawfal Rashad , Saliby Renee Maria , Semaan Karl , Steiner Clara , Heng Daniel Yick Chin , Choueiri Toni K.
Published: February 2025

509

Background:
Comorbidities pose a challenge in the treatment of patients with cancer and present a barrier to inclusion in clinical trials. While the effect of comorbidities on the efficacy of immunotherapy (IO) has been studied in various malignancies, it remains unclear in patients with metastatic renal cell carcinoma (mRCC) treated with IO-based combinations.
Methods:
Data from patients with mRCC receiving IO-based combinations (IO+IO or IO+anti-vascular endothelial growth factor (VEGF)) as first-line treatment were collected from the Dana-Farber Cancer Institute and the Tom Baker Cancer Centre-University of Calgary. The comorbidity burden was assessed at baseline using the Charlson Comorbidity Index (CCI). Patients were stratified into two groups: CCI-low (≤3) or CCI-high (>3), to predict overall survival (OS) through maximally selected rank statistics. The effect of CCI on OS and time-to-treatment failure (TTF) was assessed using multivariable Cox regression models.
Results:
Overall, 311 patients were included. The median age was 63 years (Q1-Q3: 58-69), and most patients had clear-cell mRCC (89.7%). A total of 167 (53.7%) and 144 (46.3%) patients were treated with IO+IO and IO+anti-VEGF, respectively. The most prevalent comorbidities were cardiovascular disease (20.2%) and diabetes (18.6%). In terms of CCI, 241 (77.5%) and 70 (22.5%) patients were categorized as CCI-low and CCI-high, respectively. Median follow-up was 40.8 months (Q1-Q3: 34.4-47.2) for OS. OS (aHR: 1.89, 95% CI: 1.16-3.06, p=0.010) and TTF (aHR: 1.56, 95% CI: 1.04-2.33, p=0.029) were worse in the CCI-high group (vs. CCI-low group) after adjusting for covariates (IMDC groups, age, Karnofsky score, histology, sarcomatoid features, sites of metastases, treatment type, and nephrectomy status). Rates of all adverse events (AEs) (66% vs. 65.5%) and immune-related AEs (42.1% vs. 35.9%) were comparable between the CCI-low and CCI-high groups, respectively.
Conclusions:
We report for the first time that comorbidity burden is an adverse prognostic factor in patients with mRCC undergoing IO-based combinations, highlighting the need for multidisciplinary care and tailored treatment strategies in this vulnerable patient population. Interestingly, despite the observed difference in survival outcomes, the incidence and profile of AEs were similar between the high- and low-comorbidity groups, suggesting that comorbidity burden does not substantially alter the safety profile of IO-based treatments.
Long follow-up quality of life outcomes from an investigator-initiated randomized trial of enzalutamide versus abiraterone plus prednisolone in docetaxel-untreated castration-resistant prostate cancer.
Authors: Izumi Kouji , Mizokami Atsushi
Published: February 2025

52

Background:
Head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) demonstrated similar survival benefit for castration-resistant prostate cancer. We analyzed quality of life (QOL) reported over time in each treatment arm as sub-analysis study.
Methods:
ENABLE study for PCa, an investigator-initiated, multicenter, phase 3 randomized controlled trial, was conducted. FACT-G QOL questionnaires were reported by patients at timepoints. We analyzed questionnaires up to 48 months, including the detailed assessment of subscales which consist of physical, social, emotional, and functional well-being.
Results:
In total 92 patients in each arm included, 79 and 77 in the ENZ and ABI arm answered questionnaires up to 24 months. There were no significant differences in overall survival and time to PSA progression between arms (P=0.4365 and P=0.2458). Although ENZ did not change the total score of FACT-G during treatment (P=0.8552), ABI significantly deteriorated it gradually (P=0.0002). In ABI arm, the standard dose (1000 mg/day) significantly deteriorated the total score of FACT-G chronologically (n=57, P=0.0002), meanwhile the modified dose (750 mg/day or less) did not change it during treatment (n=15, P=0.1816). In the subscale analysis, ENZ did not deteriorate any subscales, whereas ABI deteriorated social and functional well-beings (P=0.0149 and P=0.0005, respectively). Further dissection of subscale analysis revealed that the modified dose of ABI did not deteriorate social and functional well-beings (P=0.277 and P=0.4026, respectively) but the standard dose of ABI significantly deteriorated them (P=0.0010 and P<0.0001, respectively).
Conclusions:
A head-to-head comparison of QOL between ENZ- and ABI-treated castration-resistant prostate cancer patients was performed for the first time. ABI deteriorated QOL chronologically and the standard dose of ABI was a main cause of the deterioration in QOL. The modified dose of ABI may be a better treatment option. Clinical trial information:
UMIN000015529
.
Organ perforation and fistula formation as adverse events in patients receiving tyrosine kinase inhibitors: A post-market analysis.
Authors: Myint Zin , Li Ning , Ellis Carleton Scott , Whitesell Ashlyn War , Yan Donglin
Published: February 2025

528

Background:
Vascular Endothelial Growth Factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs), such as lenvatinib and cabozantinib, offer significant survival benefits in solid tumors, including renal cell carcinoma (RCC), thyroid cancer, hepatocellular carcinoma, and endometrial cancer. However, rare but serious adverse events (AEs), such as organ perforation and fistula formation, have been reported. This study evaluates the incidence and risk of these events in patients treated with VEGF-TKIs using post-marketing data from the FDA Adverse Event Reporting System (FAERS).
Methods:
We queried the FAERS database for reports of organ perforation and fistula formation associated with cabozantinib, lenvatinib, axitinib, and tivozanib from January 1, 2012, to June 30, 2024. A disproportionality analysis was performed using reporting odds ratios (ROR) to assess the association between VEGF-TKIs and these adverse events. Cases were categorized by organ site, with a focus on gastrointestinal (GI) tract-related events.
Results:
We identified 65,194 reports, including 917 cases of organ perforation and 482 cases of fistula formation. Among the perforation cases, 245 (27%) were intestinal, followed by gastric (5%). Fistula cases included 11% anal, 9% female genital tract and 6% were GI-related. Regarding TKI distribution, 19% of perforation cases were linked to cabozantinib, 35% to lenvatinib, and 46% to other TKIs (axitinib, tivozanib, or multiple TKIs). For fistula cases, 18% were associated with cabozantinib, 41% with lenvatinib, and 41% with other TKIs. Among these reports, 27% of perforations and 20% of fistulas occurred in patients with RCC. Disproportionality analysis revealed a significantly higher risk of both organ perforation (ROR: 3.41, 95% CI: 2.36–4.93) and fistula formation (ROR: 17.06, 95% CI: 14.46–20.12) in VEGF-TKI treated patients.
Conclusions:
Patients treated with VEGF-targeted TKIs, particularly lenvatinib, have a significantly increased risk of organ perforation and fistula formation. Lenvatinib was associated with a higher incidence of these adverse events compared to cabozantinib. These findings highlight the need for increased clinical awareness and monitoring, particularly in patients with RCC. Further research is necessary to better understand the mechanisms underlying these complications and to develop preventive strategies.