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COPENHAGEN, Denmark—Among patients with severe aortic stenosis at low- or intermediate-risk for surgery who also have very calcified aortic valves, SAVR is associated with lower risks of all-cause mortality, paravalvular regurgitation, and heart failure hospitalization compared with TAVI, according to new single-center data.

“[A] calcium score could potentially be an important criteria to consider when deciding between TAVI versus SAVR in low- and intermediate-risk patients,” said Fadi Hage, MD (Lankenau Medical Center, Wynnewood, PA), who presented the findings at the 2025 European Association for Cardio-Thoracic Surgery meeting. “Further investigation into predictors of outcomes in lower-risk patients is warranted to improve patient selection and [make] a more informed heart team discussion.”

Session moderator Alicja Zientara, MD (Universitätsklinikum Freiburg, Germany), said the results highlight the need for imaging in assessing patients for TAVI.

“It’s not only about the clinical risk factors of patients and choosing the right valve, but very much about imaging and evaluating if a TAVR is very well feasible for a patient,” she told TCTMD. “We know that there is a risk of aortic regurgitation and there is a risk of pacemaker, and not every patient necessarily is the right one for this kind of treatment. So, we as surgeons have to work very much on implementing regular imaging in our daily practice to also evaluate the valve, like cardiologists do.”

Better Outcomes With SAVR

The analysis included 227 patients who underwent TAVI (mean age 82 years; 77% male) and 99 who had SAVR (mean age 68 years; 88% male) at their institution between June 2021 and December 2023. All patients were considered low-to-intermediate risk for surgery and had a high aortic valve calcium score (≥ 3,000 Agatston units). More patients in the TAVI arm had peripheral vascular disease (20% vs 6%) and fewer had bicuspid aortic valve anatomy (4% vs 39%) than in the surgery arm.

In a propensity score-matched analysis, survival at 2 years was higher in the SAVR arm compared with TAVI (HR 0.17; P = 0.001). The same relationship was seen for freedom from paravalvular regurgitation (HR 0.05; P = 0.001) and heart failure rehospitalization (HR 0.33; P = 0.045). Unadjusted analyses showed advantages for SAVR over TAVI with regard to survival and freedom from paravalvular regurgitation, but not freedom from heart failure rehospitalization.

There was a higher risk of new permanent pacemaker with TAVI compared with SAVR at 30 days (16% vs 6%; P = 0.01), but a lower rate of postoperative transfusion (7% vs 36%; P < 0.001).

During the discussion, session panelist Ferdinand Vogt, MD (Paracelsus Medical University Nürnberg, Germany), pointed out a challenge for surgeons. “In the real world, we don’t have for every surgical patient an Agatston score,” he said, questioning whether this creates a “bias” in real-world practice when patients are deciding between TAVI and surgery.

“It would be an important thing to consider,” Hage responded, adding that it’s not “very difficult to get” this information.

In an informal poll of the audience, about one-third in the room raised their hands indicating that they do send patients for calcium score imaging before the procedure.

Zientara said she was “a little” surprised by how few of the attendees use this kind of imaging in their workups. “But on the other hand, it’s always a hot topic,” she added. “We have new guidelines for the treatment of those patients where there are different opinions.”

Panelist Gregory Fontana, MD (Cardiovascular Institute of Los Robles Health System, Thousand Oaks, CA), commented that CT scans prior to SAVR have “become the gold standard” at his institution.

Hage, too, said he calculates his own CT measurements for each patient, enabling him to be “nonbiased.” As surgeons, he added, “we should select the right procedure for the right patients.”

WASHINGTON — NASA’s acting administrator says he plans to “open up the contract” SpaceX holds to land astronauts on the moon for the Artemis 3 mission because the company has fallen behind schedule.

In appearances on CNBC and Fox News on Oct. 20, NASA Acting Administrator Sean Duffy said NASA would allow other companies to compete to land astronauts on the moon for Artemis 3, a mission currently assigned to SpaceX’s Starship under a Human Landing System (HLS) contract awarded in 2021.

“SpaceX had the contract for Artemis 3,” Duffy said on CNBC. “The problem is they’re behind. They push their timelines out, and we’re in a race against China. The president and I want to get to the moon in this president’s term.”

“So, I’m going to open up the contract,” he continued. “I’m going to let other space companies compete with SpaceX, like Blue Origin, and again, whatever one can get us there first, to the moon, we’re going to take.”

Duffy made similar remarks on Fox News. “SpaceX has the contract. SpaceX is an amazing company. They do remarkable things, but they’re behind schedule,” he said. “So, I’m in the process of opening that contract up.”

“We’re going to have a space race in regard to American companies competing to see who can actually get us back to the moon first,” he said.

Duffy did not explain how such a “space race” would work or how it would be funded. Asked for further details, Bethany Stevens, NASA’s press secretary, provided only transcripts of Duffy’s television appearances. Most of NASA’s public affairs staff are currently furloughed because of the government shutdown that began Oct. 1.

The comments are the first public acknowledgment by NASA’s acting leader that development of the HLS version of Starship is behind schedule. Duffy previously maintained that Artemis 3 would launch in 2027, the agency’s official target, even as multiple Starship test flight failures earlier this year made that timeline increasingly unlikely.

In late July, Duffy told social media influencers attending the Crew-11 launch that SpaceX executives, including company president Gwynne Shotwell, assured him Starship would be ready for Artemis 3. “They feel very comfortable on Starship. They feel like they’re on pace for the lander,” he said then. “They said if there’s a holdup for Artemis 3, it’s not going to be them.”

After former NASA Administrator Jim Bridenstine told a Senate committee in September it was unlikely the United States would return humans to the moon before China’s first crewed landing, Duffy pushed back. “We are going to beat the Chinese to the moon. We are going to make sure that we do this safely. We’re going to do it fast. We’re going to do it right,” he said in an internal NASA town hall, without suggesting a change in approach for Artemis 3.

In his Oct. 20 interviews, Duffy acknowledged that Artemis 3 likely would not launch in 2027. On CNBC, after discussing Artemis 2’s planned launch as soon as next February, he said that “Artemis 3 comes a couple years after that.”

One of the competitors Duffy mentioned was Blue Origin, which has a separate HLS award to develop its Blue Moon Mark 2 lander for missions beginning with Artemis 5. The company reportedly has studied ways to adapt its smaller Blue Moon Mark 1 lander for a crewed mission, although one industry source described those concepts as “jury-rigged” and noted that Mark 1 currently cannot lift off from the lunar surface with any useful payload.

Other companies are also examining lunar lander concepts. “Throughout this year, Lockheed Martin has been performing significant technical and programmatic analysis for human lunar landers that would provide options to NASA for a safe solution to return humans to the moon as quickly as possible,” Bob Behnken, vice president of exploration and technology strategy at Lockheed Martin Space, said in a statement.

“We have been working with a cross-industry team of companies, and together we are looking forward to addressing Secretary Duffy’s request to meet our country’s lunar objectives,” he said, without providing details about the Lockheed lander concept.

SpaceX Chief Executive Elon Musk appeared unconcerned about potential competition. “They won’t,” he said in a social media post responding to a comment that it was “silly” to think another company would have a lander ready before Starship. “SpaceX is moving like lightning compared to the rest of the space industry.”

“Moreover, Starship will end up doing the whole moon mission. Mark my words,” he added.

Related

Commercial shipping accounts for 3 percent of all greenhouse gas emissions globally. As the sector sets climate goals and chases a carbon-free future, nuclear power — long used as a source for military vessels — presents an enticing solution. To date, however, there has been no clear, unified public document available to guide design safety for certain components of civilian nuclear ships. A new “Nuclear Ship Safety Handbook” by the MIT Maritime Consortium aims to change that and set the standard for safe maritime nuclear propulsion.

“This handbook is a critical tool in efforts to support the adoption of nuclear in the maritime industry,” explains Themis Sapsis, the William I. Koch Professor of Mechanical Engineering at MIT, director of the MIT Center for Ocean Engineering, and co-director of the MIT Maritime Consortium. “The goal is to provide a strong basis for initial safety on key areas that require nuclear and maritime regulatory research and development in the coming years to prepare for nuclear propulsion in the maritime industry.”

Using research data and standards, combined with operational experiences during civilian maritime nuclear operations, the handbook provides unique insights into potential issues and resolutions in the design efficacy of maritime nuclear operations, a topic of growing importance on the national and international stage. 

“Right now, the nuclear-maritime policies that exist are outdated and often tied only to specific technologies, like pressurized water reactors,” says Jose Izurieta, a graduate student in the Department of Mechanical Engineering (MechE) Naval Construction and Engineering (2N) Program, and one of the handbook authors. “With the recent U.K.-U.S. Technology Prosperity Deal now including civil maritime nuclear applications, I hope the handbook can serve as a foundation for creating a clear, modern regulatory framework for nuclear-powered commercial ships.”

The recent memorandum of understanding signed by the U.S. and U.K calls for the exploration of “novel applications of advanced nuclear energy, including civil maritime applications,” and for the parties to play “a leading role informing the establishment of international standards, potential establishment of a maritime shipping corridor between the Participants’ territories, and strengthening energy resilience for the Participants’ defense facilities.”

“The U.S.-U.K. nuclear shipping corridor offers a great opportunity to collaborate with legislators on establishing the critical framework that will enable the United States to invest on nuclear-powered merchant vessels — an achievement that will reestablish America in the shipbuilding space,” says Fotini Christia, the Ford International Professor of the Social Sciences, director of the Institute for Data, Systems, and Society (IDSS), director of the MIT Sociotechnical Systems Research Center, and co-director of the MIT Maritime Consortium.

“With over 30 nations now building or planning their first reactors, nuclear energy’s global acceptance is unprecedented — and that momentum is key to aligning safety rules across borders for nuclear-powered ships and the respective ports,” says Koroush Shirvan, the Atlantic Richfield Career Development Professor in Energy Studies at MIT and director of the Reactor Technology Course for Utility Executives.

The handbook, which is divided into chapters in areas involving the overlapping nuclear and maritime safety design decisions that will be encountered by engineers, is careful to balance technical and practical guidance with policy considerations.

Commander Christopher MacLean, MIT associate professor of the practice in mechanical engineering, naval construction, and engineering, says the handbook will significantly benefit the entire maritime community, specifically naval architects and marine engineers, by providing standardized guidelines for design and operation specific to nuclear powered commercial vessels.

“This will assist in enhancing safety protocols, improve risk assessments, and ensure consistent compliance with international regulations,” MacLean says. “This will also help foster collaboration amongst engineers and regulators. Overall, this will further strengthen the reliability, sustainability, and public trust in nuclear-powered maritime systems.”

Anthony Valiaveedu, the handbook’s lead author, and co-author Nat Edmonds, are both students in the MIT Master’s Program in Technology and Policy (TPP) within the IDSS. The pair are also co-authors of a paper published in Science Policy Review earlier this year that offered structured advice on the development of nuclear regulatory policies.

“It is important for safety and technology to go hand-in-hand,” Valiaveedu explains. “What we have done is provide a risk-informed process to begin these discussions for engineers and policymakers.”

“Ultimately, I hope this framework can be used to build strong bilateral agreements between nations that will allow nuclear propulsion to thrive,” says fellow co-author Izurieta.

Impact on industry

“Maritime designers needed a source of information to improve their ability to understand and design the reactor primary components, and development of the ‘Nuclear Ship Safety Handbook’ was a good step to bridge this knowledge gap,” says Christopher J. Wiernicki, American Bureau of Shipping (ABS) chair and CEO. “For this reason, it is an important document for the industry.”

The ABS, which is the American classification society for the maritime industry, develops criteria and provides safety certification for all ocean-going vessels. ABS is among the founding members of the MIT Maritime Consortium. Capital Clean Energy Carriers Corp., HD Korea Shipbuilding and Offshore Engineering, and Delos Navigation Ltd. are also consortium founding members. Innovation members are Foresight-Group, Navios Maritime Partners L.P., Singapore Maritime Institute, and Dorian LPG.

“As we consider a net-zero framework for the shipping industry, nuclear propulsion represents a potential solution. Careful investigation remains the priority, with safety and regulatory standards at the forefront,” says Jerry Kalogiratos, CEO of Capital Clean Energy Carriers Corp. “As first movers, we are exploring all options. This handbook lays the technical foundation for the development of nuclear-powered commercial vessels.”

Sangmin Park, senior vice president at HD Korea Shipbuilding and Offshore Engineering, says “The ‘Nuclear Ship Safety Handbook’ marks a groundbreaking milestone that bridges shipbuilding excellence and nuclear safety. It drives global collaboration between industry and academia, and paves the way for the safe advancement of the nuclear maritime era.”

Maritime at MIT

MIT has been a leading center of ship research and design for over a century, with work at the Institute today representing significant advancements in fluid mechanics and hydrodynamics, acoustics, offshore mechanics, marine robotics and sensors, and ocean sensing and forecasting. Maritime Consortium projects, including the handbook, reflect national priorities aimed at revitalizing the U.S. shipbuilding and commercial maritime industries.

The MIT Maritime Consortium, which launched in 2024, brings together MIT and maritime industry leaders to explore data-powered strategies to reduce harmful emissions, optimize vessel operations, and support economic priorities.

“One of our most important efforts is the development of technologies, policies, and regulations to make nuclear propulsion for commercial ships a reality,” says Sapsis. “Over the last year, we have put together an interdisciplinary team with faculty and students from across the Institute. One of the outcomes of this effort is this very detailed document providing detailed guidance on how such effort should be implemented safely.”

Handbook contributors come from multiple disciplines and MIT departments, labs, and research centers, including the Center for Ocean Engineering, IDSS, MechE’s Course 2N Program, the MIT Technology and Policy Program, and the Department of Nuclear Science and Engineering.

MIT faculty members and research advisors on the project include Sapsis; Christia; Shirvan; MacLean; Jacopo Buongiorno, the Battelle Energy Alliance Professor in Nuclear Science and Engineering, director, Center for Advanced Nuclear Energy Systems, and director of science and technology for the Nuclear Reactor Laboratory; and Captain Andrew Gillespy, professor of the practice and director of the Naval Construction and Engineering (2N) Program.

“Proving the viability of nuclear propulsion for civilian ships will entail getting the technologies, the economics and the regulations right,” says Buongiorno. “This handbook is a meaningful initial contribution to the development of a sound regulatory framework.”

“We were lucky to have a team of students and knowledgeable professors from so many fields,” says Edmonds. “Before even beginning the outline of the handbook, we did significant archival and history research to understand the existing regulations and overarching story of nuclear ships. Some of the most relevant documents we found were written before 1975, and many of them were stored in the bellows of the NS Savannah.”

The NS Savannah, which was built in the late 1950s as a demonstration project for the potential peacetime uses of nuclear energy, was the first nuclear-powered merchant ship. The Savannah was first launched on July 21, 1959, two years after the first nuclear-powered civilian vessel, the Soviet ice-breaker Lenin, and was retired in 1971.

Historical context for this project is important, because the reactor technologies envisioned for maritime propulsion today are quite different from the traditional pressurized water reactors used by the U.S. Navy. These new reactors are being developed not just in the maritime context, but also to power ports and data centers on land; they all use low-enriched uranium and are passively cooled. For the maritime industry, Sapsis says, “the technology is there, it’s safe, and it’s ready.”

“The Nuclear Ship Safety Handbook” is publicly available on the MIT Maritime Consortium website and from the MIT Libraries. 

LONDON/GENEVA – The Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) today welcomed a new £6 million investment by GSK plc (LSE/NYSE: GSK) and ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, to strengthen community-led responses to HIV, tuberculosis (TB) and malaria in lower income countries. The commitment will be matched by the Gates Foundation, bringing this total investment in the Global Fund to £12 million.

Deborah Waterhouse, CEO, ViiV Healthcare and President, Global Health GSK said: “We are proud to deepen our partnership with the Global Fund through this catalytic investment, which will help accelerate community-led responses to high burden infectious diseases such as HIV, tuberculosis, and malaria. We believe that sustainable health impact begins with empowering communities and the local organisations that know them best. By supporting programmes that are led by countries, community-owned and community-driven, we’re helping to build stronger, more resilient health systems where they’re needed most.”

The Rt Hon Yvette Cooper MP, Foreign Secretary for the United Kingdom, said: “The Global Fund has saved 70 million people from AIDS, TB and malaria since 2002. But the fight isn’t over. Climate change is contributing to a rise in malaria cases, HIV stigma still stops people from seeking treatment, and TB kills more people than any other infectious disease.

“As the UK co-hosts the Global Fund’s 8th replenishment with South Africa, it’s really welcome and important to see British business stepping up. Private sector investment and innovation is key to finding new treatments, improving access to care and ultimately ending AIDS, TB and malaria – because we know that global challenges won’t be solved if we wait until they land on our own doorstep.”

The announcement was made at a high-level event in London, marking a key milestone on the road to the 8th Replenishment Pledging Summit in November. The event showcased the power of partnership and solidarity to end AIDS, TB and malaria, building on recent momentum, catalyzing further commitments, and positioning the campaign for a successful pledging summit.

The Global Fund’s 8th Replenishment, which will finance programmes for the 2027–2029 grant cycle, is being co-hosted by the Republic of South Africa and the United Kingdom. With just five weeks to go until the Replenishment Summit, the Global Fund has raised over US$3billion, including more than US$1 billion from private sector donors – a significant portion of which has come from British philanthropy.

Hon. Ronald Lamola, Minister of International Relations and Cooperation of the Republic of South Africa, said, “South Africa is proud to co-host the Global Fund’s 8th Replenishment, and we welcome the renewed commitment from GSK and ViiV Healthcare to innovation and equity in global health. Partnerships like these — between governments, the private sector, and communities — are essential to sustain progress against HIV and malaria. As we look toward the pledging summit, South Africa calls on all partners to match this spirit of solidarity and ambition, so that together we can build a healthier, more resilient world for all.”

GSK and ViiV Healthcare have long led innovation in the fight against HIV, malaria and TB, developing solutions that have helped to reduce the burden on communities most affected by highly prevalent infectious diseases. Their advances include a portfolio of medicines and vaccines which are used in the global setting for the treatment and prevention of diseases such as malaria and HIV, and a pipeline which includes research programmes for a next generation malaria vaccine and HIV medicines, and a vaccine candidate for TB – being developed in partnership with Gates MRI, Gates Foundation and Wellcome, all aimed at helping to accelerate the progress toward ending these diseases.

“The Global Fund continues to demonstrate how partnership can drive innovation and deliver impact where it’s needed most,” said Joe Cerrell, Managing Director, Europe, the Middle East and East Asia of the Gates Foundation. “As part of our ongoing commitment, we’re announcing up to $100 million in matching funds to unlock greater private and philanthropic investment. We’re proud that the first contribution – £6 million from GSK and ViiV Healthcare – will activate this matching support. This collaboration underscores the Global Fund’s unique ability to turn bold ideas into real-world results, and we hope it will inspire others to join us in accelerating progress against HIV, TB, and malaria.”

Through this new investment with the Global Fund, GSK and ViiV Healthcare are continuing to go beyond scientific innovation, to help improve health outcomes for communities in lower income countries. The funding will support locally led partners and programmes accelerating progress in some of the world’s most affected regions. This commitment reinforces the vital role of grassroots leadership in shaping sustainable health solutions and comes at a pivotal time in the global health response, when catalytic funding for community-owned and community-led change is more important than ever.

“This commitment from GSK and ViiV Healthcare sends a powerful message – when public and private actors unite around a shared vision, we can drive real, lasting change,” said Peter Sands, Executive Director of the Global Fund. “We deeply appreciate their generosity and leadership at this critical moment. The innovation of the private sector is central to our partnerships progress, and the renewed pledge will continue our work to ensure those most impacted by infectious diseases, including women and girls, can access the best care when they need it.”

Catalytic funds, such as the one supported through this new pledge, are designed to tackle high-impact, high-priority initiatives that complement country allocations – driving innovation and accelerating progress in areas where it is most needed, for underserved communities.

Early and ambitious private sector commitments like this one are instrumental in building momentum, strengthening confidence in collective action, and inspiring others to contribute to the global effort to end HIV, TB, and malaria.

Adjuvant atezolizumab (Tecentiq) generated a significant improvement in disease-free survival (DFS) and overall survival (OS) compared with placebo in patients with muscle-invasive bladder cancer (MIBC) who were positive for circulating tumor DNA (ctDNA) by serial testing, according to data from the phase 3 IMvigor11 trial (NCT04660344).¹

Findings presented at the 2025 ESMO Congress and simultaneously published in the New England Journal of Medicine demonstrated that, at a median follow-up of 16.1 months, patients who tested positive for ctDNA and were treated with atezolizumab (n = 167) achieved a median DFS of 9.9 months (95% CI, 7.2-12.7) compared with 4.8 months (95% CI, 4.1-8.3) for those given placebo (n = 83), per investigator assessment (HR, 0.64; 95% CI, 0.47-0.87; P = .0047). The DFS benefit was consistent per independent review (HR, 0.69; 95% CI, 0.48-0.91), and an improvement was also observed with atezolizumab in terms of invasive DFS (HR, 0.66; 95% CI, 0.47-0.94).²

Additionally, ctDNA-positive patients in the atezolizumab arm experienced a median OS of 32.8 months (95% CI, 27.7-not evaluable [NE]) compared with 21.1 months (95% CI, 14.7-NE) for those in the placebo arm (HR, 0.59; 95% CI, 0.39-0.90; P = .0131).¹

“Serial ctDNA testing is a novel approach in this setting. One could argue it’s more accurate than the radiology [assessments] we’re using, and perhaps we can start looking at these diseases differently, beyond bladder cancer. Instead of telling patients that they’ve got the all clear and then radiologically [have their] cancer return, we can be doing tests looking for MRD and identifying early metastatic disease, bringing a new ctDNA-positive, radiology-negative group of patients,” lead study author Thomas Powles, MBBS, MRCP, MD, said in a presentation of the data.

Powles is a professor of genitourinary oncology, director of the Barts Cancer Centre at St. Bartholomew’s Hospital, and lead for Solid Tumor Research at Queen Mary University in London.

IMvigor11 Highlights

• Adjuvant atezolizumab improved DFS and OS vs placebo in patients with MIBC who were positive for ctDNA after radical cystectomy.

• Efficacy benefits were observed in patients who were ctDNA positive at baseline and those who converted to ctDNA positivity upon subsequent testing.

• Serial ctDNA testing could play a role in identifying patients with MIBC who could benefit from adjuvant atezolizumab, as well as sparing unnecessary treatment for patients with ctDNA-negative disease.

Why could the IMvigor11 trial be important for the MIBC treatment paradigm?

Radical cystectomy with or without neoadjuvant therapy represents a potential curative option for patients with MIBC, but Powles explained that disease recurrence remains a challenge and is associated with a poor prognosis.

Previously reported data from the phase 3 IMvigor10 trial (NCT02450331) showed that adjuvant atezolizumab did not produce DFS or OS benefits vs placebo in patients MIBC who were unselected for ctDNA.³ However, an exploratory analysis from that trial showed that patients who were positive for ctDNA after cystectomy experienced an OS benefit, whereas those with ctDNA-negative disease did not have a survival benefit.¹

“[IMvigor10] is an example of one of the big negative trials that we’ve performed in bladder cancer. The group…went back to [IMvigor10] and performed an exploratory analysis, [then] launched a subsequent phase 3 [study (IMvigor11)] based on that,” Powles explained.

Thusly, the IMvigor11 trial sought to further explore the potential role of adjuvant atezolizumab in ctDNA-positive MIBC.

How as the IMvigor11 trial designed?

Investigators enrolled patients with MIBC who underwent radical cystectomy within 6 to 24 weeks of screening. Patients needed to have histologically confirmed (y)pT2-T4aN0M0 or (y)pT0-T4aN+M0 urothelial cancer with no evidence of radiographic disease progression. Prior neoadjuvant therapy was allowed, and patients needed to have an ECOG performance status of 0 to 2.

Enrolled patients underwent serial ctDNA testing every 6 weeks and radiographic imaging every 12 weeks, and serial ctDNA testing was continued for any patients who tested negative. The Signatera MRD test was used for ctDNA detection for patients enrolled outside mainland China, and those in China were tested using the BGI MRD test.

Patients who remained ctDNA negative for up to 1 year did not receive any treatment, and surveillance continued with follow-up. Patients who tested positive for ctDNA at any point without evidence of radiographic disease were randomly assigned in a 2:1 ratio to receive atezolizumab at 1680 mg once every 4 weeks for up to 1 year, or matching placebo.

Investigator-assessed DFS served as the trial’s primary end point, and OS was a key secondary end point.

During the study, 379 patients tested positive for ctDNA at any point, and 377 patients remained in persistent ctDNA negativity. In the ctDNA-positive population, 129 patients were excluded dur to investigator-assessed radiographic recurrence (n = 72), independent review–assessed radiographic recurrence, and other (n = 34). Furthermore, 250 ctDNA-positive patients were randomly assigned and included in the efficacy population; the safety population included 248 patients who received treatment with either atezolizumab (n = 165) or placebo (n = 83).

At the data cutoff, 8 patients were ongoing treatment in the experimental arm vs 4 patients in the placebo arm. Ninety-two and 35 patients, respectively, remained in follow-up; 67 and 44 patients, respectively, discontinued the study.

In the ctDNA-negative population, 20 patients were excluded due to no post-baseline assessment (n = 14), insufficient follow-up (n = 5), and no cystectomy (n = 1). Overall, 357 patients were evaluable for efficacy in the ctDNA-negative population; 310 completed or were continuing surveillance. Forty-seven patients discontinue the study due to investigator-assessed radiographic progression (n = 18), patient withdrawal (n = 14), death (n = 11), and other (n = 4).

Within the ctDNA-positive population, the median age was 69 years (range, 42-87) in the atezolizumab arm vs 67 years (range, 44-84) in the placebo arm. Most patients in both groups were male (atezolizumab, 84.4%; placebo, 80.7%), were from Europe (60.5%; 59.0%), had an ECOG performance status of 0 (67.7%; 63.9%), had a PD-L1 expression of less than 5% (64.7%; 63.9%), did not receive neoadjuvant chemotherapy (52.1%; 60.2%), had positive nodal status (57.5%; 57.8%), were less than 20 weeks removed from cystectomy to first positive ctDNA sample (70.1%; 71.1%), and were ctDNA positive on their initial test (59.3%; 59.0%).

What other data were reported in the ctDNA-positive population?

The DFS and OS benefits with atezolizumab were consistent across subgroups in the ctDNA-positive population. Specifically, patients who tested positive for ctDNA on their initial test experienced a median investigator-assessed DFS of 8.3 months (95% CI, 6.2-12.6) with atezolizumab (n = 99) vs 4.2 months (95% CI, 2.4-7.7) with placebo (n = 49; HR, 0.62; 95% CI, 0.42-0.91). For patients who tested positive for ctDNA on a subsequent test, the median DFS was 10.5 months (95% CI, 7.1-14.6) with atezolizumab (n = 68) vs 8.3 months (95% CI, 4.2-12.6) with placebo (n = 34; HR, 0.66; 95% CI, 0.40-1.10).

In the ctDNA-positive population, the median OS for patients positive at their first test was 27.7 months (95% CI, 22.0-35.9) with atezolizumab vs 18.2 months (95% CI, 10.9-NE) with placebo (HR, 0.71; 95% CI, 0.43-1.17). The median OS was NE (95% CI, 34.4-NE) with atezolizumab vs 27.4 months (95% CI, 18.1-NE) with placebo in those patients who tested positive for ctDNA after the initial screening (HR, 0.52; 95% CI, 0.24-1.12).

Additionally, ctDNA clearance at cycle 3, day 1, or cycle 5, day 1 occurred in 25.1% of patients in the atezolizumab arm vs 14.5% of patients in the placebo arm.

Disease recurrence occurred in 63.5% of patients in the atezolizumab arm vs 78.3% of patients in the placebo arm; 51.5% and 54.2%, respectively, received follow-up therapy. In the atezolizumab arm, 48.5% of patients completed first-line therapy, 17.4% finished second-line therapy, 4.2% completed third-line therapy, and 1.2% finished fourth-line therapy. These respective rates were 51.8%, 21.7%, 4.8%, and 1.2% in the placebo arm. Subsequent treatments in the experimental arm included chemotherapy at 36.5%, immunotherapy at 15.6%, an antibody-drug conjugate at 19.2%, and other at 6.0%. These respective rates were 31.3%, 31.3%, 19.3%, and 4.8% in the control arm.

What were the safety outcomes for atezolizumab vs placebo?

In the ctDNA-positive population, any-grade adverse effects (AEs) were reported in 83.6% of patients in the atezolizumab arm vs 85.5% of patients in the placebo arm; the rates of grade 3/4 AEs were 28.5% and 21.7%, respectively. Any-grade treatment-related AEs (TRAEs) occurred at respective rates of 49.1% and 50.6%, and the rates of grade 3/4 TRAEs were 7.3% and 3.6%, respectively. Serious AEs occurred in 26.7% of patients in the experimental arm vs 20.5% of patients in the control arm; the rates of serious TRAEs were 5.5% and 0%, respectively.

AEs led to death in 3.0% of patients in the atezolizumab arm compared with 2.4% of patients in the placebo arm. TRAEs led to death in 1.8% of patients in the experimental arm vs no patients in the placebo arm.

AEs led to treatment discontinuation and treatment interruption in 9.1% and 23.6% of patients in the atezolizumab arm, respectively. These respective rates were 3.6% and 19.3% in the placebo group.

Immune-mediated AEs of any grade were reported in 38.8% of patients in the atezolizumab arm vs 12.0% of patients in the control arm. The respective rates of grade 3/4 immune-mediated AEs were 4.8% and 1.2%. Immune-mediated AEs led to death in 0.6% of patients in the atezolizumab group vs no patients in the control group.

What were the efficacy outcomes in the ctDNA-negative population?

At a median follow-up of 21.8 months for evaluable ctDNA-negative patients who underwent surveillance, the median DFS was NE (95% CI, NE-NE), with 1- and 2-year DFS rates of 95.4% and 88.4%, respectively.The median OS was also NE (95% CI, NE-NE), with 1- and 2-year OS rates of 100% and 97.1%, respectively.

References

1. Powles T, Kann AG, Castellano D, et al. IMvigor011: a phase 3 trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA8.
2. Powles T, Kann AG, Castellano D, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. N Engl J Med. Published online October 20, 2025. doi:10.1056/NEJMoa2511885
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