Exploration of Targeted Anti-tumor Therapy

Table 1. Characteristics of the included studies (n = 15).

Study	Design	Cancer type	Sample/population	Key outcome(s)	ctDNA method
Del Re et al., 2021 [7]	Original	Prostate, mCRPC	n = 84	AR gain in cfDNA (14.3%) + AR-V7 in exosomes (35.7%) predict primary ARSI resistance; combined-aberration PFS 3.8 vs. 28 months (P < 0.0001)	cfDNA + exosomes (ddPCR)
Isebia et al., 2025 [8]	Original, prospective	Prostate, mCRPC	n = 196	Baseline GWA-high predicts poor ARSI response (HR 2.63) but not taxanes; early GWA-high predicts both (HR 6.73/2.79)	cfDNA aneuploidy (mFast-SeqS)
Sweeney et al., 2024 [9]	Ph III biomarker (secondary analysis)	Prostate, mCRPC	n = 494	ctDNA TF at C3D1 predicts OS; mOS 22.1 vs. 16.0 months (ctDNA-undetected/PSA-not-reduced vs. ctDNA-detected/PSA-reduced; P < 0.001)	Tissue-agnostic plasma (FoundationOne Monitor)
Kwan et al., 2022 [3]	Narrative review	Prostate, mCRPC	NR	Implementation pathways: prognosis, monitoring, genotyping; CHIP misattribution risk 15–20%	Multi-platform overview
Lindskrog et al., 2023 [10]	Original, 2-cohort longitudinal	Urothelial, MIBC	n = 170 (68 + 102)	Post-RC ctDNA: 94% sensitivity/98% specificity for relapse; NAC-naïve post-RC HR 17.8 (P = 0.0002)	Signatera tumor-informed mPCR-NGS
Nawaf et al., 2023 [11]	Narrative review	Urothelial, MIBC	NR	IMvigor010 ctDNA-stratified adjuvant atezolizumab benefit (HR 0.59); TOMBOLA/IMvigor011 ongoing	Signatera + trial landscape
Katsimperis et al., 2025 [12]	Narrative review	Urothelial, MIBC	NR	Tumor-informed vs. agnostic testing; perioperative risk stratification, MRD, bladder-sparing rationale	Multiple
Crocetto et al., 2025 [13]	Systematic review (qualitative)	Urothelial, NMIBC-MIBC	NR	Broader liquid biopsy landscape (urine methylation, CTC, ctDNA); ctDNA one component	Multi-analyte
Del Re et al., 2022 [14]	Original, prospective	Renal, mccRCC	n = 48	cfDNA > 0.883 ng/µL + TP53mut predict shorter PFS (7.23 vs. NR months; P = 0.001) and OS (23.9 vs. NR months; P = 0.008)	cfDNA quantity + Oncomine NGS
Kato et al., 2025 [15]	Original, nationwide cohort	Renal, mRCC	n = 124	TF < 1.2% → better PFS (HR 0.467); BAP1 mutation → poor OS (HR 0.487); new mutations at progression in 46.8%	SCRUM-Japan MONSTAR-SCREEN NGS panel
Alam et al., 2025 [16]	Case series	Renal, diverse histologies	n = 6	Serial ctDNA guided adjuvant/salvage decisions in all 6 cases; authors note lower sensitivity/NPV in kidney cancers	Signatera
Jikuya et al., 2025 [17]	Narrative review	Renal	NR	Lower ctDNA shedding vs. other tumors; no routine treatment-selection biomarker yet; EVs as complementary analyte	Multi liquid biopsy
Nakano et al., 2022 [18]	Original, prospective	UTUC, perioperative	n = 50	Preoperative ctDNA fraction > 2% independently predicts worse RFS; CHIP caused 19% false-positive TP53 calls	Oncomine Pan-Cancer cfDNA (CHIP-filtered)
Jang et al., 2023 [19]	Original, pilot prospective	Mixed GU (RCC 15, UC 4, PC 1), advanced/ICI	n = 20	ctDNA-imaging concordance 83% (15/18); ORR 70%; CNS metastases a discordance blind spot	Signatera tumor-informed
Gerke et al., 2024 [2]	Narrative review	Mixed GU	NR	Cross-site overview of detection/prognosis/monitoring; RCC flagged as highest unmet need	Multiple

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This table describes the 15 studies included in the narrative synthesis (see in ctDNA in RCC: emerging evidence and current limitations section). Distribution by design: original research = 8 (53.3%); narrative reviews = 5 (33.3%); systematic review (qualitative) = 1 (6.7%); case series = 1 (6.7%); the IMbassador250 ctDNA biomarker analysis (Sweeney et al. [9]) and the SCRUM-Japan MONSTAR-SCREEN cohort (Kato et al. [15]) are counted as original research. All percentage denominators refer to n = 15. mCRPC: metastatic castration-resistant prostate cancer; AR: androgen receptor; AR-V7: AR splice variant 7; ARSI: AR signaling inhibitor; PFS: progression-free survival; ddPCR: digital droplet polymerase chain reaction; GWA: genome-wide aneuploidy; HR: hazard ratio; TF: tumor fraction; C3D1: cycle 3, day 1; mOS: median overall survival; PSA: prostate-specific antigen; NR: not reported; not reached (survival estimates); CHIP: clonal hematopoiesis of indeterminate potential; MIBC: muscle-invasive bladder cancer; Post-RC: post-radical cystectomy; NAC: neoadjuvant chemotherapy; mPCR: multiplex polymerase chain reaction; NGS: next-generation sequencing; MRD: minimal residual disease; NMIBC: non- MIBC; CTC: circulating tumor cell; mccRCC: metastatic clear cell renal cell carcinoma; TP53: tumor protein p53; OS: overall survival; mRCC: metastatic renal cell carcinoma; NPV: negative predictive value; EVs: extracellular vesicles; UTUC: upper tract urothelial carcinoma; RFS: recurrence-free survival; GU: genitourinary; RCC: renal cell carcinoma; UC: urothelial carcinoma; PC: prostate cancer; ICI: immune checkpoint inhibitor; ORR: objective response rate; CNS: central nervous system.

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/1002407_sup_1.pdf.

Declarations

Acknowledgments

AI-assisted bibliometric tools (SCITE.ai) were used solely as a secondary verification aid for reference integrity and contextual classification, as described in the main text; final scientific judgment for all search, screening, extraction, and inclusion/exclusion decisions was exercised entirely by the two human authors, in accordance with the journal’s policy on AI-assisted technologies.

Author contributions

AC: Conceptualization, Methodology, Investigation, Writing—original draft, Writing—review & editing, Supervision. APBG: Methodology, Investigation, Writing—review & editing. Both authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

This integrative review analyzed published literature only; no new primary data were generated. The included studies are listed in Table 1 and the References and are accessible through the databases listed in the Methods (PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science). The per-database search strategies are provided in the Supplementary material. Additional supporting data (screening and extraction records) are available from the corresponding author upon request.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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