The second week of August brought together important updates across GU oncology, with expert posts covering prostate cancer, urothelial carcinoma, bladder cancer, renal cell carcinoma, germ cell tumors, and non-muscle-invasive bladder cancer.
This week’s selection includes updates on HER1–HER4 expression and co-expression in advanced urothelial carcinoma, PARP inhibitors in metastatic prostate cancer, PROpel and HRR gene mutations in metastatic castration-resistant prostate cancer, active surveillance trends in favorable-risk prostate cancer, and treatment outcomes in mCRPC from the TRUMPET Registry.
Other posts highlight LITESPARK-011 with belzutifan plus lenvatinib in advanced clear cell RCC, overlapping genetic etiology of pediatric and adult germ cell tumors, key JAMA prostate cancer publications on active surveillance, focal therapy, and SBRT, lifestyle inflammation and outcomes in NMIBC, and focal therapy use in nonmetastatic prostate cancer.
Together, these posts reflect the continued evolution of GU oncology across biomarker-driven therapy, precision medicine, active surveillance, focal therapy, radiotherapy, real-world evidence, tumor genetics, treatment sequencing, and survivorship-focused research.
Sara Coca Membribes — Medical Oncologist, Clinical Research Fellow in GU Oncology | Barts Cancer Institute | United Kingdom
“Pleased to share our latest work, now published in ESMO Open.
As HER-targeted antibody-drug conjugates continue to reshape the treatment landscape in urothelial carcinoma, most attention has understandably focused on HER2.
However, HER2 expression is heterogeneous, and an increasing number of agents are now targeting other members of the HER family.
In this study, we characterized HER1–HER4 expression and co-expression in advanced urothelial carcinoma using tumor samples collected within a prospective randomized clinical trial.
We found that HER receptors were rarely expressed in isolation: 96% of tumors expressed at least 2 HER receptors, and 61% co-expressed all four.
These findings provide a biological rationale for HER-targeted ADCs beyond HER2, including emerging dual-targeted strategies. Izalontamab brengitecan is being tested in IZABRIGHT-Bladder01, NCT07106762.
In an exploratory analysis, HER1 expression was associated with lower platinum response rates, whereas HER3 and HER4 were associated with higher response rates.
We also found distinct expression patterns across molecular subtypes, with HER2 enriched in luminal tumors and HER3 in basal tumors.
I am very grateful to Tom Powles and Charlotte Ackerman for their mentorship and support, and to everyone at Barts Cancer Institute, Queen Mary University of London, who contributed to this work.”
María Natalia Gandur Quiroga — GU Medical Oncologist, Head of GU Tumours, Ángel H. Roffo Oncology Institute, University of Buenos Aires | Argentina
“How far can we extend the benefit of PARP inhibitors in metastatic prostate cancer?
Recent advances continue to reinforce the role of PARP inhibitors, particularly in patients with BRCA1/2 alterations.
But an important question remains: how can we identify other patients who may benefit?
This review explores the evolving evidence around PARP inhibitors, including combination strategies with androgen receptor pathway inhibitors, molecular stratification, biomarker refinement, and their potential application in earlier stages of prostate cancer.
Beyond treatment efficacy, the challenge is increasingly about understanding which patients are most likely to benefit, and when.
An interesting review for anyone following the evolution of precision medicine in prostate cancer.
What do you think will be the next major step in expanding the role of PARP inhibitors?”
Giuseppe Procopio — Chief of Genitourinary Oncology | Director Prostate Program | Full Professor Qualified | FICOG and Meet-URO President | Italy
“New insights into precision medicine for metastatic castration-resistant prostate cancer.
A new analysis from the phase 3 PROpel trial, published in European Urology Oncology, provides further insight into the efficacy of olaparib plus abiraterone according to individual homologous recombination repair gene mutations.
Among 796 patients enrolled in PROpel, 28.4% had an HRR gene mutation, with BRCA2, ATM, and CDK12 representing the most prevalent single-gene alterations.
The analysis showed the greatest treatment benefit in patients with BRCA2 mutations, with outcomes favoring olaparib plus abiraterone versus placebo plus abiraterone for both:
• rPFS: HR 0.20, 95% CI 0.08–0.44
• OS: HR 0.20, 95% CI 0.07–0.48
Numerical improvements were also observed in patients with ATM and CDK12 mutations, although the smaller number of patients in these subgroups limits definitive conclusions.
These findings add another important piece to our understanding of the molecular heterogeneity of prostate cancer and reinforce the role of genomic testing in treatment planning, helping to identify patients who may derive the greatest benefit from targeted therapeutic strategies.
Ultimately, integrating molecular information into clinical decision-making is becoming increasingly important as we move toward a more precise and personalized approach to the treatment of advanced prostate cancer.”
Read the full article
Matt Cooperberg — Professor at University of California, San Francisco | United States
“Out in JAMA today from Grace Lee et al.: trends from the national U.S. Department of Veterans Affairs VAHCS database.
Active surveillance is now the first management strategy for 93% of men with low-risk prostate cancer and 62% of those with favorable intermediate-risk disease.
This is huge progress and shows the VA absolutely leading the way in quality of care in this domain.”
Neal Shore — Medical Director, CPI – Carolina Urologic Research Center, Director, START GU Oncology Center of Excellence | United States
“Treatment and outcomes of patients with metastatic castration-resistant prostate cancer by race, initial diagnosis, and family history: results from the TRUMPET Registry.”
Enrique Grande — Medical Oncologist, Medical Oncology Department Director at Quironsalud Madrid | Spain
“LITESPARK-011 was published in The Lancet: belzutifan plus lenvatinib versus cabozantinib in advanced clear cell renal cell carcinoma after anti-PD-1 or anti-PD-L1 therapy.
The study included 747 patients.
Median PFS was 14.8 months with belzutifan plus lenvatinib versus 10.7 months with cabozantinib, with HR 0.70.
Overall survival was not significantly different at interim analysis, with HR 0.85.”
Shannon M. Sullivan — Assistant Professor, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School | United States
“I am excited to share our new paper in JNCI: Journal of the National Cancer Institute: ‘Overlapping Genetic Etiology of Pediatric and Adult Germ Cell Tumors.’
Germ cell tumors are rare tumors that can appear almost anywhere in the body, including the testes, ovaries, brain, chest, or abdomen in children and adolescents.
For years, we have known that adult testicular cancer has strong genetic risk factors. However, we did not know whether those same genes matter in younger patients and for tumors outside the testes.
Using data from 1,927 pediatric germ cell tumor patients, the largest collection to date, we found:
• 4 risk loci near BAK1, SPRY4, DMRT1, and DEPTOR
• 6 loci linked specifically to intracranial germ cell tumors, including 4 completely novel findings
• 18 of the 78 known adult testicular cancer genes also appeared in pediatric germ cell tumor patients, providing strong evidence of shared biology
• Strong genetic overlap between pediatric intracranial germ cell tumors and adult testicular cancer
• Evidence that shared biology across ages, sexes, and tumor locations traces back to early germ cell development, supporting the idea that these tumors, however different they look clinically, may share a common origin story
This is a big step toward understanding why these tumors happen and, eventually, identifying children at increased genetic risk.”
Himanshu Nagar — Director of Genitourinary Program and Manhattan Chief of External Beam Radiotherapy, Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center | United States
“JAMA published 3 important prostate cancer publications, with accompanying editorials recommended:
- Active surveillance is increasing in the VA population, which is encouraging.
- Focal therapy use is increasing, which is concerning.
- SBRT gains more data for intermediate-risk prostate cancer in NRG GU 005, which is reassuring.”
Joann Kiebach — PhD candidate at Radboudumc | MSc Nutrition and Health from Wageningen University & Research | Netherlands
“I am excited to share our latest work and the second paper of my PhD research, published in Nutrition.
Using data from approximately 1,300 patients with non-muscle-invasive bladder cancer in the UroLife cohort, we investigated whether a pro-inflammatory lifestyle, measured by the Lifestyle Inflammation Score, a pro-inflammatory diet, measured by the Dietary Inflammation Score, and systemic inflammation, measured by hsCRP after diagnosis, were associated with recurrence and progression.
We found that more pro-inflammatory lifestyle and dietary patterns were associated with higher hsCRP levels, confirming that these scores capture systemic inflammation.
However, neither LIS, DIS, nor hsCRP were associated with recurrence or progression risk in our cohort.
These findings highlight the complexity of the relationship between lifestyle, inflammation, and cancer outcomes.
They also illustrate that biologically plausible mechanisms do not always translate into observable differences in clinical outcomes, highlighting the need to better understand pathways and factors influencing prognosis after cancer diagnosis.
Many thanks to my supervisors, collaborators, and all participants who made this research possible.”
Adam B. Weiner, MD — Urologic Oncologist at Cedars Sinai Medical Center | United States
“Half of focal therapy for prostate cancer in the United States is happening where no guideline supports it.
A JAMA research letter included 1,179,384 patients with nonmetastatic prostate cancer from the National Cancer Database between 2010 and 2023.
Overall, 15,672 patients, or 1.3%, received focal therapy.
Among those who received focal therapy, 51% had low-, high-, or very high-risk disease.
No guideline supports routine use of focal therapy in any risk group outside trials or registries.
Use in low-risk disease remained relatively flat, from 1.8% to 2.2%, while use in favorable intermediate-risk disease increased from 2.1% to 2.9%.
Focal therapy was more likely among patients aged 75 years or older, with adjusted probability 22.9%, in community centers, 7.6% versus 2.5% in academic centers, and among patients with nonprivate insurance.
From the accompanying editorial: ‘Volume of this kind shows diffusion, not benefit.’
The key point is that in low-risk disease, focal therapy can convert surveillance candidates into procedure patients, while in high-risk disease, it may represent undertreatment.
Repeated use is building ‘an aura of legitimacy the data have not earned.’
We owe patients trials, not marketing.”
Find out 10 Must-Read Posts in GU Oncology from the first week of August on OncoDaily.