Neoadjuvant, adjuvant, and perioperative systemic therapy in urothelial cancers: Evolving paradigms and future directions

Praloy Basu

doi:10.25259/ASJO_29_2026

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Review Article

2026

:12;

doi:

10.25259/ASJO_29_2026

Neoadjuvant, adjuvant, and perioperative systemic therapy in urothelial cancers: Evolving paradigms and future directions

Praloy Basu^1,_{MBBS, MD, DM}

1Department of Medical Oncology, Desun Hospital, Kolkata, West Bengal, India.

*Corresponding author: Praloy Basu, Medical Oncology, Desun Hospital, 720, Eastern Metropolitan Bypass, Golpark, Kasba, Kolkata, 700107, West Bengal, India. dr.praloybasu@gmail.com

Received: 2026-04-03, Accepted: 2026-06-01, Published: 2026-08-18

Licence

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Basu P. Neoadjuvant, adjuvant and perioperative systemic therapy in urothelial cancers: Evolving paradigms and future directions. Asian J Oncol. 2026;12:26. doi: 10.25259/ASJO_29_2026

Abstract

Radical surgery is the cornerstone of management for localized muscle-invasive urothelial carcinoma (MIUC), yet surgery alone cures only a proportion of patients because occult micrometastatic disease is common at diagnosis. Over the last two decades, perioperative systemic treatment has evolved from a cisplatin-based chemotherapy paradigm to a more complex framework incorporating immune checkpoint inhibitors, antibody-drug conjugates, biomarker-enriched strategies, and risk-adapted postoperative approaches. Cisplatin-based neoadjuvant chemotherapy remains a foundational standard in cisplatin-eligible muscle-invasive bladder cancer (MIBC), supported by randomized trials and meta-analyses demonstrating improved pathologic downstaging and overall survival. However, real-world delivery is limited by renal dysfunction, frailty, hearing loss, neuropathy, and physician or patient reluctance to delay definitive surgery. Adjuvant chemotherapy has been more difficult to establish in bladder cancer because of postoperative attrition and underpowered trials, although the EORTC 30994 study and the upper tract POUT trial support postoperative platinum-based treatment in selected high-risk settings. Single-agent neoadjuvant immunotherapy produced encouraging pathologic complete response (pCR) rates in phase II studies such as PURE-01 and ABACUS, laying the groundwork for modern perioperative immunotherapy.

The perioperative field has changed substantially with positive phase III studies. NIAGARA established perioperative Durvalumab plus neoadjuvant Gemcitabine-cisplatin followed by adjuvant Durvalumab as a new standard for cisplatin-eligible MIBC, improving event-free survival and overall survival. AMBASSADOR showed that adjuvant Pembrolizumab improves disease-free survival after radical surgery in high-risk MIUC, broadening postoperative immune checkpoint inhibition beyond Nivolumab. Most recently, KEYNOTE-905/EV-303 demonstrated that perioperative Enfortumab vedotin plus Pembrolizumab improves event-free survival, overall survival, and pCR versus surgery alone in cisplatin-ineligible or cisplatin-declining MIBC, filling one of the most important historical gaps in perioperative treatment.

This review summarizes the biological rationale, evidence base, current standards, unresolved controversies, and future directions for neoadjuvant, adjuvant, and perioperative systemic therapy in urothelial cancers, including bladder and upper tract disease. Particular emphasis is placed on patient selection, regimen choice, endpoints, biomarker development, and integration of the latest phase III data into clinical practice.

Keywords

Antibody–drug conjugates (ADC)

Immunotherapy

Peri-operative therapy

Systemic therapy

Urothelial cancers

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INTRODUCTION

Urothelial carcinoma (UC) is characterized by a high risk of systemic relapse despite optimal local therapy. Radical cystectomy remains the cornerstone for muscle-invasive bladder cancer (MIBC), yet recurrence rates remain substantial due to occult micrometastatic disease. This biological reality underpins the development of perioperative systemic therapy.

Over the past two decades, treatment paradigms have evolved from chemotherapy alone to include immune checkpoint inhibitors (ICIs) and antibody–drug conjugates (ADCs). The perioperative approach now encompasses neoadjuvant, adjuvant, and integrated perioperative strategies, with recent phase III trials reshaping standards of care.

The modern discussion is no longer limited to “neoadjuvant or adjuvant chemotherapy.” It now includes perioperative chemoimmunotherapy in cisplatin-eligible disease, perioperative antibody-drug conjugate plus immunotherapy in cisplatin-ineligible disease, postoperative immune checkpoint blockade after surgery, and biomarker-guided escalation or de-escalation strategies. The challenge for clinicians is to integrate these data into coherent treatment pathways that are biologically rational, logistically feasible, and evidence-based.

BIOLOGICAL RATIONALE FOR PERIOPERATIVE SYSTEMIC THERAPY

Neoadjuvant therapy enables early eradication of micrometastatic disease and benefits from intact tumor vasculature, improving drug delivery. It also allows in vivo assessment of response, with pathologic complete response (pCR) correlating with improved outcomes.

Adjuvant therapy targets residual disease in high-risk patients but is limited by postoperative morbidity and reduced eligibility for systemic therapy.

Perioperative strategies combine both philosophies. They seek to exploit the biological advantages of preoperative treatment while continuing systemic therapy after surgery to suppress residual microscopic disease over a longer interval. This concept has become especially relevant in immunotherapy, where sustained immune modulation after resection might consolidate preoperative antitumor activity. NIAGARA and KEYNOTE-905 are archetypal perioperative trials and provide proof that such a strategy can improve survival in properly selected patients.

NEOADJUVANT CISPLATIN-BASED CHEMOTHERAPY IN MIBC

The modern standard for cisplatin-eligible MIBC was established by randomized trials demonstrating that preoperative platinum-based combination chemotherapy improves outcomes over surgery alone. In SWOG-8710, neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) followed by radical cystectomy improved median survival compared with cystectomy alone and increased the rate of pT0 at surgery.^[1] The broader evidentiary foundation was consolidated by the Advanced Bladder Cancer Meta-analysis Collaboration, which showed that cisplatin-based neoadjuvant chemotherapy produced an overall survival benefit and reduced the risk of death.^[2] A subsequent Cochrane review supported this conclusion and helped cement neoadjuvant cisplatin-based chemotherapy as standard care in fit patients.^[3]

The impact of neoadjuvant chemotherapy derives from both systemic disease control and pathologic response. pCR after neoadjuvant therapy is associated with excellent long-term outcomes, while substantial downstaging to non–muscle-invasive residual disease also portends better survival. These observations made pCR and pathologic downstaging central to later phase II immunotherapy studies and continue to influence trial design in the field. However, a critical nuance is that pCR is a surrogate, not a definitive substitute for survival. Regimens that improve pCR do not always produce a proportionate overall survival gain, especially if toxicity limits treatment delivery or if the biologic effect is confined to a subset of patients.

Despite strong evidence, real-world uptake of neoadjuvant cisplatin remains disappointingly modest. Many patients are cisplatin-ineligible because of reduced glomerular filtration rate, performance status, hearing loss, neuropathy, or heart failure. Others are technically eligible but do not receive treatment because of concerns about delaying surgery, limited referral pathways, age bias, or patient preference. This implementation gap is important when interpreting newer postoperative or perioperative trials: some studies partly reflect not only drug efficacy but also the historical underuse of preoperative cisplatin. In current practice, whenever feasible, cisplatin-based neoadjuvant treatment remains the benchmark against which new perioperative strategies must be judged.

Choice of neoadjuvant regimen

Although classic MVAC established proof of principle, Gemcitabine-cisplatin (GC) became widely used because of familiarity and tolerability, even though the randomized perioperative evidence base was initially less direct than for MVAC. The GETUG-AFU V05 VESPER program helped refine regimen selection. In VESPER, dose-dense MVAC (ddMVAC) outperformed GC for progression-free outcomes in the neoadjuvant subset and has often been interpreted as supporting dd-MVAC as the preferred regimen in fit patients who can tolerate it.^[4-6] dd-MVAC also achieved higher pathologic complete response and organ-confined response rates in secondary analyses, although toxicity profiles and supportive care requirements remain relevant when choosing among regimens.

The neoadjuvant standard, therefore, consists not merely of “any platinum doublet” but ideally a well-delivered cisplatin-based combination, with dd-MVAC and GC being the dominant options. The debate today is less about whether neoadjuvant cisplatin works and more about how it should be integrated with immunotherapy. NIAGARA, for example, used GC as the chemotherapy backbone, showing that the addition of Durvalumab can improve outcomes beyond chemotherapy alone. This result is clinically important because it builds on a regimen already familiar to many centers and may accelerate adoption of perioperative chemoimmunotherapy in daily practice.

ADJUVANT CHEMOTHERAPY

Compared with neoadjuvant therapy, adjuvant chemotherapy in bladder cancer has less uniform evidence base. Several postoperative studies were underpowered, closed early, or were complicated by crossover and delayed chemotherapy in the control arm. The EORTC 30994 trial compared immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3/ pT4 and/or node-positive disease. The trial did not show a statistically significant overall survival benefit for immediate treatment, but the interpretation was limited by inadequate power and treatment heterogeneity. ^[4] Consequently, adjuvant cisplatin-based chemotherapy has often been regarded as reasonable in selected high-risk patients who did not receive neoadjuvant therapy and remain fit for cisplatin after surgery, rather than as a universally mandated standard.

Adjuvant chemotherapy is conceptually attractive in patients upstaged at cystectomy after no neoadjuvant treatment, especially those with pT3/4 or pN+ disease. Yet postoperative renal decline is common after urinary diversion, and recovery from surgery can be prolonged. These realities favor giving systemic therapy before cystectomy whenever possible. In that sense, the limitations of adjuvant chemotherapy are not only evidentiary but logistical, and they partly explain why the field moved quickly toward postoperative immunotherapy, which may be more deliverable than cisplatin in a postoperative population.

NEOADJUVANT IMMUNE CHECKPOINT INHIBITOR MONOTHERAPY

The first major neoadjuvant immunotherapy studies in MIBC were phase II single-arm trials designed to test feasibility and biological activity. PURE-01 evaluated three cycles of Pembrolizumab before radical cystectomy and reported striking pCR and downstaging rates, particularly in tumors with higher PD-L1 expression and higher tumor mutational burden.^[7,8] ABACUS studied two cycles of Atezolizumab before cystectomy in cisplatin-ineligible or cisplatin-refusing patients and also demonstrated meaningful pCR activity with manageable toxicity.^[9-11] These studies generated substantial enthusiasm because the pCR rates appeared competitive with historical chemotherapy outcomes despite the absence of cytotoxic chemotherapy.

Several lessons emerged from PURE-01 and ABACUS. First, neoadjuvant immunotherapy was feasible and generally did not compromise surgery, though vigilant perioperative management remained important. Second, pathologic response correlated with favorable survival outcomes in longer follow-up analyses. Third, biomarkers showed promise but were not yet sufficiently robust for routine clinical selection. PD-L1 expression, tumor mutational burden, immune infiltration, and other signatures displayed associations with response, but none consistently achieved the precision needed for stand-alone clinical decision-making.

These trials were not definitive enough to replace cisplatin-based neoadjuvant chemotherapy in eligible patients. They were small, nonrandomized, and subject to selection bias. Their chief importance was strategic: they established that the intact urothelial tumor can be highly immunogenic in the preoperative setting and justified the move to randomized chemoimmunotherapy and perioperative immunotherapy phase III trials. They also created a framework for cisplatin-ineligible investigation, a setting in which conventional neoadjuvant standards were weak.

ADJUVANT IMMUNE CHECKPOINT INHIBITION

CheckMate 274

CheckMate 274 was the first clearly positive phase III adjuvant immunotherapy trial in high-risk muscle-invasive urothelial carcinoma (MIUC) after radical surgery. Nivolumab significantly improved disease-free survival versus placebo in the intention-to-treat population, with a larger effect in the PD-L1 ≥1% subgroup.^[12] This was a watershed result because it provided a practical postoperative option for patients with residual high-risk disease, including those who had received prior neoadjuvant cisplatin and remained at substantial risk of recurrence. Longer-term follow-up continues to mature, including ctDNA analyses and 5-year data, but CheckMate 274 already changed clinical practice by establishing one year of adjuvant Nivolumab as a postoperative standard in appropriate patients.

IMvigor010

In contrast, IMvigor010 failed to show a disease-free survival benefit for adjuvant Atezolizumab over observation in an unselected high-risk postoperative population.^[13] At first glance this negative trial seemed discordant with CheckMate 274, prompting debate about assay differences, patient selection, control-arm behavior, timing, and biological distinctions between PD-1 and PD-L1 blockade. However, a major post hoc contribution of IMvigor010 was the ctDNA analysis. Patients with detectable ctDNA after surgery had a markedly worse prognosis, and this biomarker-defined group appeared to derive meaningful benefit from adjuvant Atezolizumab, whereas ctDNA-negative patients did not.^[14] This finding strongly influenced the field and directly informed subsequent ctDNA-guided studies such as IMvigor011.

Taken together, CheckMate 274 and IMvigor010 illustrate two central themes in perioperative urothelial oncology. First, postoperative checkpoint inhibition can improve outcomes, but the benefit is unlikely to be uniform across all resected high-risk patients. Second, molecular residual disease detection by ctDNA may become one of the most important tools for treatment selection, surveillance intensity, and trial enrichment.

AMBASSADOR: Adjuvant pembrolizumab after radical surgery

The Alliance A031501 AMBASSADOR study further advanced postoperative immunotherapy by comparing adjuvant Pembrolizumab with observation after radical surgery in high-risk MIUC. The study included both bladder and upper tract primaries and permitted prior neoadjuvant chemotherapy. AMBASSADOR demonstrated a statistically significant and clinically meaningful improvement in disease-free survival with Pembrolizumab.^[15] The published NEJM report established Pembrolizumab as another validated adjuvant immune checkpoint inhibitor in this setting.

The importance of AMBASSADOR extends beyond simply adding another drug option. It confirms that postoperative PD-1 blockade can improve clinically relevant outcomes versus observation, thereby reinforcing the broader principle introduced by CheckMate 274. It also provides an evidence-based alternative in settings where Nivolumab is unsuitable, unavailable, or less favored for practical reasons. Whether adjuvant Pembrolizumab and adjuvant Nivolumab should be viewed as interchangeable is less important than recognizing that both support the role of postoperative immune checkpoint inhibition for high-risk disease after surgery.

Several nuances matter when integrating AMBASSADOR into practice. First, the trial speaks most directly to patients who have undergone surgery and remain at high pathologic risk, especially those who did not receive perioperative immune therapy preoperatively. Second, as perioperative regimens such as NIAGARA and KEYNOTE-905 move upfront, the role of “purely adjuvant” immunotherapy may increasingly narrow to patients who either had upfront surgery or are found postoperatively to have unexpectedly high-risk disease. Third, overall survival maturation remains important because disease-free survival gains are meaningful, but ultimate treatment sequencing may depend on whether early checkpoint exposure improves cure rather than merely delays recurrence.

PERIOPERATIVE THERAPY

NIAGARA: Perioperative durvalumab plus neoadjuvant chemotherapy in cisplatin-eligible MIBC

NIAGARA is arguably the most practice-changing perioperative MIBC trial to date. In this phase III study, cisplatin-eligible patients with operable MIBC received neoadjuvant Durvalumab plus GC followed by radical cystectomy and adjuvant Durvalumab, or neoadjuvant GC followed by cystectomy alone. The trial met its primary efficacy goals, demonstrating superior event-free survival and overall survival for the Durvalumab-containing perioperative strategy.^[16] According to the NEJM report, NIAGARA also showed that adding Durvalumab did not meaningfully compromise the ability to proceed to surgery, addressing a major practical concern for preoperative immunotherapy combinations.

NIAGARA matters for several reasons. It validates the perioperative concept rather than merely the neoadjuvant one. The regimen uses a familiar chemotherapy backbone, improving external applicability. It demonstrates overall survival benefit, which is the most persuasive endpoint in a curative-intent population. It also shifts the standard for cisplatin-eligible patients from chemotherapy alone to chemoimmunotherapy plus postoperative immune maintenance, at least where access and regulatory approval allow.

A key conceptual question is which component of NIAGARA mattered most: the addition of Durvalumab to neoadjuvant GC, the continuation of Durvalumab after surgery, or the full integrated package. The study was not designed to isolate these contributions. Clinically, however, the answer is less important than the practical conclusion: the tested perioperative strategy improved outcomes and should be delivered as studied when selected. Another important implication is that NIAGARA raises the bar for future perioperative trials in cisplatin-eligible MIBC. New regimens now need to show benefit over a more effective comparator than neoadjuvant chemotherapy alone.

NIAGARA also influences how adjuvant immunotherapy is used. A patient who receives perioperative Durvalumab upfront does not fit the same evidence framework as a patient who undergoes upfront cystectomy and then receives postoperative Nivolumab or Pembrolizumab. As perioperative regimens move earlier, the future postoperative decision space will increasingly depend on prior systemic exposure, residual pathologic stage, and emerging biomarkers such as ctDNA.

KEYNOTE-905/ev-303: Perioperative enfortumab vedotin plus pembrolizumab in cisplatin-ineligible or cisplatin-declining MIBC

The cisplatin-ineligible population has long represented the major unmet need in localized MIBC. Historically, many such patients proceeded directly to cystectomy despite high recurrence risk because no perioperative regimen had convincingly improved overall survival. KEYNOTE-905/ EV-303 changed that landscape. This phase III trial tested perioperative Enfortumab vedotin plus Pembrolizumab plus surgery versus surgery alone in cisplatin-ineligible or cisplatin-declining patients with MIBC. The trial demonstrated superior event-free survival, overall survival, and pCR for the experimental arm.^[17] This is the first high-level evidence establishing an effective perioperative systemic option for the large group of patients unable or unwilling to receive cisplatin.

The biological logic of the regimen is strong. Enfortumab vedotin targets nectin-4, which is broadly expressed in urothelial cancer, and has already shown synergy with Pembrolizumab in advanced disease. Bringing this combination into the perioperative setting offered a way to avoid cisplatin while still providing meaningful systemic cytoreduction and immune activation. The magnitude and breadth of benefit in KEYNOTE-905 are particularly striking because they include both pathologic response and hard time-to-event endpoints.

From a clinical perspective, KEYNOTE-905 has several immediate implications. First, it creates a credible perioperative standard for cisplatin-ineligible MIBC, a space where previous management often defaulted to surgery alone. Second, it narrows the therapeutic disparity between cisplatin-eligible and cisplatin-ineligible patients. Third, it suggests that the perioperative future of urothelial cancer may not be limited to checkpoint inhibitor combinations with chemotherapy; antibody-drug conjugate–immunotherapy combinations may become equally or more important in selected populations. Finally, the trial will likely stimulate study of residual disease biology after perioperative EVPembrolizumab, because patterns of nonresponse may differ from those seen after cisplatin or checkpoint monotherapy.

One caution is that experience with perioperative EVPembrolizumab is still early relative to the decades of cisplatin data. Toxicities such as neuropathy, rash, and hyperglycemia require careful attention, especially in patients undergoing major pelvic surgery. Even so, KEYNOTE-905 is clearly one of the defining perioperative urothelial cancer studies of the current era.

UPPER TRACT UROTHELIAL CARCINOMA

UTUC differs from bladder cancer in epidemiology, anatomy, surgical consequences, and perioperative treatment logistics. After nephroureterectomy, renal function often declines, which may reduce or eliminate cisplatin eligibility. This observation has long provided a rationale for considering neoadjuvant chemotherapy in high-risk localized UTUC, because the preoperative window may be the only time some patients are fit enough for cisplatin. Nevertheless, the strongest randomized evidence in UTUC has come from postoperative treatment.

The POUT trial randomized patients with pT2-T4 and/or node-positive UTUC after nephroureterectomy to adjuvant Gemcitabine-platinum or surveillance and demonstrated a significant disease-free survival benefit.^[18] The final results confirmed sustained benefit and solidified adjuvant platinum-based chemotherapy as a standard for eligible high-risk UTUC.^[19] These findings are particularly important because randomized data in UTUC are relatively scarce.

Whether perioperative immunotherapy will reshape UTUC as dramatically as it has MIBC remains uncertain. Many perioperative bladder cancer trials included only a minority of upper tract primaries or excluded them altogether. AMBASSADOR is relevant because it includes UTUC, but disease-specific conclusions remain limited by subgroup size.

BIOMARKERS AND TREATMENT PERSONALIZATION

The central biomarker question in perioperative urothelial cancer is no longer whether biomarkers matter, but which ones are sufficiently validated for practice. PD-L1 has shown inconsistent predictive value across trials because of assay heterogeneity, different scoring systems, temporal variation, and the complexity of immune-tumor interactions. Tumor mutational burden and immune gene signatures have also shown promise, particularly in PURE-01 and ABACUS, but remain investigational for routine patient selection.

ctDNA is the most compelling current biomarker. In IMvigor010, ctDNA positivity after cystectomy strongly identified patients at the highest risk of recurrence and appeared to enrich the benefit from adjuvant Atezolizumab.^[14] This concept has now moved beyond retrospective signal generation, with ctDNA-guided adjuvant Atezolizumab showing positive phase III results in IMvigor011, although integration into routine care will depend on assay access, turnaround time, standardization, reimbursement, and guideline adoption.^[20] ctDNA may eventually serve three functions: postoperative risk stratification, treatment selection, and surveillance. A ctDNA-negative patient after contemporary perioperative therapy may be a candidate for de-escalation, whereas ctDNA positivity may justify adjuvant intensification or trial enrollment.

CURRENT PRACTICAL TREATMENT FRAMEWORK

Cisplatin-eligible MIBC: Perioperative Durvalumab + GC (NIAGARA)^[16]
Cisplatin-ineligible MIBC: EV + Pembrolizumab (KEYNOTE-905)^[17]
Postoperative high-risk disease: Adjuvant Nivolumab or Pembrolizumab^[12,15]
UTUC: Adjuvant platinum chemotherapy (POUT)^[18,19]

UNRESOLVED CONTROVERSIES AND FUTURE DIRECTIONS

Several unresolved questions remain. First, what is the optimal comparator for future trials in cisplatin-eligible MIBC now that NIAGARA is positive? Trials designed against chemotherapy alone may no longer be sufficient in jurisdictions where perioperative Durvalumab becomes standard.

Second, how should clinicians treat residual high-risk disease after modern perioperative regimens? The evidence base for “adjuvant after perioperative” therapy is thin, and simply adding more checkpoint blockade after prior exposure may not be biologically useful.

Third, pCR remains attractive but imperfect as a surrogate. It is useful for early-phase screening, but definitive practice change still requires event-free and overall survival data. NIAGARA and KEYNOTE-905 are important partly because they met those harder endpoints.

Fourth, cisplatin ineligibility itself is heterogeneous. Some patients are formally ineligible by renal criteria but otherwise robust; others are frail with competing comorbidity risks. A regimen proven in the broader cisplatin-ineligible population may not perform identically across all such subgroups.

Fifth, the role of bladder preservation with systemic intensification is expanding. Although this review focuses on surgical perioperative therapy, the success of modern systemic regimens raises the possibility that selected patients might be managed with organ-preserving trimodality approaches augmented by checkpoint blockade or novel agents.

Finally, ctDNA-guided therapy may become the organizing principle of postoperative management. Rather than treating all high-risk patients uniformly, future strategies may intensify treatment for molecular residual disease and spare therapy for those already cured by surgery and neoadjuvant treatment.

The urothelial perioperative field is therefore moving from broad risk-based treatment toward adaptive precision oncology. The decisive trials of the present era—CheckMate 274, AMBASSADOR, NIAGARA, KEYNOTE-905, and ctDNA-guided IMvigor011—are likely to be remembered not merely for changing individual standards but for redefining how perioperative therapy is conceptualized across urothelial cancers.

CONCLUSION

Perioperative systemic therapy has transformed the management of urothelial cancer. Neoadjuvant cisplatin-based chemotherapy remains foundational, but recent trials have expanded treatment options. NIAGARA establishes perioperative chemoimmunotherapy in cisplatin-eligible disease, while KEYNOTE-905 addresses the unmet need in cisplatin-ineligible patients. AMBASSADOR further strengthens the role of adjuvant immunotherapy.

Future progress will depend on biomarker integration and optimization of treatment sequencing.

Ethical approval:

Institutional Review Board approval is not required.

Declaration of patient consent:

Patient's consent not required as there are no patients in this study.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Financial support and sponsorship: Nil.

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