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RCC → Adjuvant clear-cell RCC

Last reviewed: 2026-09-22 · Next review: 2026-12-21

current — pembrolizumab has randomized DFS and OS benefit; in the US, pembrolizumab plus belzutifan is FDA-labeled with immature OS

Who this applies to

KEYNOTE-564 eligibility and decision boundary

Risk group	Exact trial definition	Adjuvant discussion
Intermediate-high risk	Clear-cell RCC: pT2 grade 4 or sarcomatoid, N0 M0; or pT3 any grade, N0 M0¹	Discuss pembrolizumab and risk-adapted surveillance¹¹⁴.
High risk	Clear-cell RCC: pT4 any grade, N0 M0; or any pT, any grade, N+ M0¹	Discuss pembrolizumab and risk-adapted surveillance¹¹⁴.
M1 NED	Primary tumor plus solid, isolated, soft-tissue, nonbone/nonbrain metastasis completely resected with negative margins synchronously or within 1 year after nephrectomy; NED at baseline¹	Discuss in a multidisciplinary setting; the subgroup is small and should not be treated as equivalent to M0 cohorts¹⁴.
Lower-risk clear-cell RCC	Does not meet a trial risk definition¹	Use risk-adapted surveillance; do not extend the trial result to lower-risk disease¹¹⁴.
Non-clear-cell RCC	Outside the KEYNOTE-564 population¹	Do not extrapolate the pembrolizumab result; discuss surveillance or a clinical trial¹¹⁴.

KEYNOTE-564 required nephrectomy and, when relevant, metastasectomy within 12 weeks before randomization¹. This is trial eligibility, not a universal treatment-start mandate¹⁴.
Confirm histology, pT/pN stage, grade, sarcomatoid features, margin status, surgery date, NED status, recovery, renal function, autoimmune history, and baseline endocrinopathy before deciding¹¹⁴.

Standard options

Circumstance	Option	Shared-decision discussion	Typical course
KEYNOTE-564–eligible clear-cell RCC	Pembrolizumab¹	Randomized benefit was versus placebo, not surveillance¹. Discuss the DFS/OS results, immune-related toxicity, and possibility of overtreatment⁴².	Trial regimen: 200 mg IV every 3 weeks for up to 17 cycles¹. The current US label also permits 400 mg IV every 6 weeks¹⁸.
US adult with intermediate-high/high-risk clear-cell RCC or qualifying M1 NED	Pembrolizumab plus belzutifan⁵¹⁹	FDA-labeled in the US¹⁸¹⁹. LITESPARK-022 showed a DFS benefit over pembrolizumab plus placebo (24-month DFS 80.7% vs 73.7%; HR 0.72), but OS was immature and grade ≥3 treatment-emergent AEs were 52.1% vs 30.2% with pembrolizumab plus placebo⁵. Do not present it as OS-proven or interchangeable with pembrolizumab alone⁵¹⁹.	Pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks plus belzutifan 120 mg orally daily; up to 1 year per label¹⁸¹⁹.
Eligible patient preferring no adjuvant systemic therapy, or with competing risk/frailty/major immune-risk concern	Risk-adapted surveillance¹⁴¹⁵	Active management option; use postoperative imaging and functional follow-up individualized to recurrence risk, renal function, and preferences¹⁴¹⁵.	Ongoing¹⁴
Non-clear-cell RCC or a patient outside the pivotal population	Clinical trial or risk-adapted surveillance¹¹⁴	There is no KEYNOTE-564 direct-evidence basis to select pembrolizumab¹.	Protocol or ongoing¹⁴

EAU timing after restaging—not trial eligibility

The EAU RCC guideline strongly recommends offering adjuvant pembrolizumab after restaging, preferably 12–16 weeks after nephrectomy, to patients with KEYNOTE-564-defined risk¹⁴. It also directs shared discussion of the discordant adjuvant-ICI trials, overtreatment, and immune-related adverse effects¹⁴.

Surveillance and treatment de-escalation

EAU Leibovich-adapted imaging (chest + abdomen CT; abdominal MRI alternative)

Risk (ccRCC Leibovich 2003)	3 mo	6 mo	12 mo	18 mo	24 mo	30 mo	36 mo	After year 3	After year 5
Low (score 0–2)¹⁴	—	CT	—	CT	—	CT	—	CT every 2 years¹⁴	Consider stopping oncologic imaging based on age/comorbidity/preference¹⁴
Intermediate (score 3–5)¹⁴	—	CT	CT	—	CT	—	CT	Annual CT¹⁴	CT every 2 years; consider stopping after year 5¹⁴
High (score ≥6)¹⁴	CT	CT	CT	CT	CT	—	CT	Annual CT¹⁴	CT every 2 years¹⁴

Phase	Labs / on-treatment monitoring	Stop, hold, or de-escalate	Re-escalation / next line
Risk-adapted surveillance (no adjuvant)¹⁴¹⁵	Renal function and blood pressure with imaging visits¹⁴.	No systemic therapy when outside KEYNOTE-564 eligibility or patient declines¹¹⁴.	Recurrence → metastatic RCC page or metastasectomy discussion for oligometastatic disease¹⁴¹⁵.
Adjuvant pembrolizumab (± belzutifan US label)¹⁸²	CBC, CMP, TSH every 3 weeks (or q6wk if q6wk pembro); immune-symptom review each visit¹⁸².	Complete up to 17 cycles (pembro) or 1 year per label unless progression or toxicity; hold for grade ≥3 immune events¹¹⁸. Belzutifan continues with pembro for labeled duration; OS immature for combination—shared decision to stop at 1 year⁵¹⁹.	Recurrence on or after adjuvant → mRCC page; prior adjuvant PD-1 exposure informs first-line metastatic choice¹⁴¹⁵.

KEYNOTE-564 DFS/OS curves already appear under Landmark evidence (source-recreated); use them when counseling surveillance versus adjuvant pembrolizumab³⁴.
EAU recommends offering adjuvant pembrolizumab after restaging, preferably 12–16 weeks post-nephrectomy, for KEYNOTE-564-defined risk¹⁴.

Landmark evidence

KEYNOTE-564: practice-changing DFS and OS

KEYNOTE-564 full source-recreated disease-free and overall survival curves

Approximate source-recreated full Kaplan–Meier traces digitized from the published KEYNOTE-564 DFS and OS figures at the September 15, 2023 data cutoff; no journal artwork or individual-patient data are reproduced³. Exact published 12-, 24-, 36-, and 48-month estimates are labeled³. Intermediate curve positions are approximate visual digitization and must not be read as reported landmark estimates³.

Cross-trial comparison

Trial results are not head-to-head efficacy comparisons: eligibility, recurrence risk, M1 NED inclusion, treatment exposure, endpoint assessor, and comparator differ¹⁴. Hazard ratios and published landmark rates are reported where available.

Trial	Population	Intervention	Comparator	Primary endpoint	Clinically meaningful outcomes	Generalizability-critical differences
KEYNOTE-564, NCT03142334	994 ccRCC with intermediate-high/high risk or qualifying M1 NED after nephrectomy ± metastasectomy¹⁴	Pembrolizumab 200 mg IV every 3 weeks for ≤17 cycles¹	Matching placebo¹	Investigator-assessed DFS¹	5-year DFS 60.9% vs 52.2% (HR 0.71)⁴. 5-year OS 87.7% vs 82.3% (HR 0.66)⁴.	ccRCC only; includes qualifying M1 NED but not lower-risk disease¹. Direct evidence base for adjuvant pembrolizumab¹⁴.
LITESPARK-022, NCT05239728	1,841 ccRCC at increased recurrence risk after nephrectomy⁵	Pembrolizumab 400 mg IV every 6 weeks for ≤9 doses + belzutifan 120 mg orally daily⁵	Pembrolizumab 400 mg IV every 6 weeks + placebo⁵	Investigator-assessed DFS⁵	24-month DFS 80.7% vs 73.7% (HR 0.72)⁵. OS HR 0.78 (P=.24) at 29% of planned events; immature⁵.	Add-on trial against pembrolizumab, not pembrolizumab vs surveillance; does not test pembrolizumab monotherapy’s effect versus placebo⁵.
S-TRAC, NCT00375674	615 locoregional, high-risk ccRCC after nephrectomy⁶	Sunitinib 50 mg orally daily, 4 weeks on/2 weeks off, for 1 year⁶	Placebo⁶	Blinded independent central review DFS⁶	Median DFS 6.8 vs 5.6 years (HR 0.76; P=.03); OS immature⁶.	Clear-cell, high-risk population; different recurrence-risk definition and VEGFR-TKI mechanism from the ICI trials⁶.
ASSURE, NCT00326898	1,943 completely resected nonmetastatic RCC, including clear-cell and non-clear-cell; high-grade pT1b or greater⁷	Sunitinib or sorafenib for 54 weeks⁷	Placebo⁷	DFS for each active arm vs placebo⁷	5-year DFS: sunitinib 54.3%, sorafenib 54.0%, placebo 56.4%; HR 1.02 and 0.97, respectively⁷.	Only trial here including non-clear-cell RCC and a lower-risk high-grade pT1b threshold; broader population than KEYNOTE-564⁷.
PROTECT, NCT01235962	1,538 resected pT2 high-grade or ≥pT3/N1 ccRCC⁸	Pazopanib daily for 1 year; starting dose reduced from 800 to 600 mg⁸	Placebo⁸	DFS in the protocol-amended 600-mg intention-to-treat population⁸	Primary DFS HR 0.86 (95% CI 0.70–1.06; P=.165); final OS HR 1.00⁸.	ccRCC only and M0; primary dose/population changed after safety attrition, so the secondary 800-mg DFS signal is not comparable with the primary result⁸.
ATLAS, NCT01599754	724 RCC with >50% clear-cell component, ≥pT2 and/or N+, no macroscopic residual/metastatic disease⁹	Axitinib 5 mg orally twice daily for ≤3 years⁹	Placebo⁹	Independent review committee DFS⁹	Stopped for futility; DFS HR 0.87 (95% CI 0.66–1.15; P=.32)⁹. Highest-risk subgroup IRC analysis HR 0.74 (P=.0704)⁹.	Entry included ≥pT2 disease, potentially lower risk than S-TRAC; highest-risk finding is subgroup evidence, not a positive primary endpoint⁹.
IMmotion010, NCT03024996	778 RCC with clear-cell or sarcomatoid component and increased recurrence risk, including an M1 NED stratum¹⁰	Atezolizumab 1,200 mg IV every 3 weeks for 16 cycles¹⁰	Placebo¹⁰	Investigator-assessed DFS¹⁰	Median DFS 57.2 vs 49.5 months (HR 0.93; P=.50)¹⁰.	Histology criterion and risk definitions differ from KEYNOTE-564; negative PD-L1 inhibitor trial does not establish a class effect¹⁰.
CheckMate 914 Part A, NCT03138512	816 localized, predominantly ccRCC, M0, after partial/radical nephrectomy 4–12 weeks earlier¹¹	Nivolumab 240 mg IV every 2 weeks ×12 + ipilimumab 1 mg/kg IV every 6 weeks ×4¹¹	Matching placebo¹¹	Blinded independent central review DFS¹¹	24-month DFS 76% vs 74% (HR 0.92; P=.53)¹¹. Grade 3–5 AEs 38% vs 10%¹¹.	M0 only; excluded active autoimmune disease or substantial immunosuppression, used a shorter course, and did not include M1 NED¹¹.
CheckMate 914 Part B, NCT03138512	Separate 825-participant cohort with the same localized, predominantly ccRCC M0 eligibility¹³	Nivolumab 240 mg IV every 2 weeks for ≤12 doses¹³	Placebo¹³	Blinded independent central review DFS¹³	18-month DFS 78.4% vs 75.4% (HR 0.87; P=.40)¹³. OS immature¹³.	Same M0-only and immunosuppression/autoimmunity boundaries as Part A; different regimen duration and no M1 NED¹³.
PROSPER ECOG-ACRIN EA8143, NCT03055013	819 previously untreated clinical T2+ or any-N+ RCC, clear-cell or non-clear-cell; selected oligometastatic NED eligible¹²	One preoperative nivolumab 480 mg dose → surgery → nine adjuvant doses¹²	Surgery followed by observation¹²	Investigator-reviewed RFS¹²	Stopped for futility; RFS HR 0.94 (95% CI 0.74–1.21; one-sided P=.32)¹².	Perioperative, open-label strategy with an observation comparator; includes non-clear-cell and selected oligometastatic disease, so it is not an adjuvant-only placebo comparison¹².

Biomarkers

Marker	Current clinic role	Emerging / investigational	How it changes decision now	Limits
Clear-cell + KEYNOTE-564 risk features	Direct-evidence selection for adjuvant pembrolizumab¹	—	Defines who is inside the pivotal population for adjuvant discussion¹.	Confirm on nephrectomy pathology; do not extend benefit claims to non-clear-cell or lower-risk disease¹.
Leibovich score (2003)	Risk-adapted surveillance imaging intensity (EAU)¹⁴	—	Sets chest/abdomen CT cadence for observation after nephrectomy¹⁴.	Prognostic imaging framework only; not a substitute for KEYNOTE-564 adjuvant eligibility¹¹⁴.
PD-L1	Not a routine adjuvant selector¹¹⁴	Exploratory correlatives in adjuvant ICI trials¹¹⁴	Does not select who receives adjuvant pembrolizumab¹¹⁴.	No validated threshold for adjuvant benefit¹¹⁴.
ctDNA / MRD	Not standard for adjuvant selection¹⁴	MRD GATE RCC testing MRD-guided observation vs pembrolizumab in KEYNOTE-564–eligible ccRCC¹⁴	Do not withhold adjuvant therapy for a negative MRD result outside a trial¹⁴.	Assay performance and decision thresholds are not practice-ready on this page¹⁴.
Tumor genomic / expression signature	Not used to select adjuvant pembrolizumab¹⁴	Investigational molecular classifiers¹⁴	No change to adjuvant or surveillance choice today¹⁴.	No validated assay for this setting¹⁴.
Germline evaluation	Hereditary-risk assessment when age, bilateral/multifocal disease, family history, or syndrome features raise concern¹⁴¹⁷	Broader panel testing when indicated¹⁴¹⁷	Informs genetic counseling and contralateral/family risk; not adjuvant drug selection¹⁴¹⁷.	Does not replace KEYNOTE-564 pathology criteria¹¹⁴.

Upcoming research

Field direction: adjuvant pembrolizumab remains the DFS-proven anchor; intensifying with HIF-2 (LITESPARK-022), broadening ICI platforms (RAMPART), and MRD- or VEGFR-guided strategies (MRD GATE RCC, STRIKE) are the next experiments⁵¹⁴¹¹⁵.

Trial or publication	Why it may change care	Evidence status
LITESPARK-022 mature follow-up	Clarifies whether the established DFS advantage of pembrolizumab plus belzutifan over pembrolizumab alone becomes an OS advantage and how durable the added toxicity is⁵.	Peer-reviewed phase 3 publication; OS immature at the reported analysis⁵. Study follow-up remains active⁵.
RAMPART, NCT03288532	Tests adjuvant durvalumab alone or with tremelimumab against active monitoring in resected RCC, including non-clear-cell disease; longer follow-up may contextualize the discordant ICI-trial results¹⁴.	Phase 3 platform. Enrollment closed in June 2023; congress reporting and OS follow-up are pending peer-reviewed maturity¹⁴.
MRD GATE RCC, NCT06005818	Tests whether an MRD-guided strategy can safely observe MRD-negative, otherwise KEYNOTE-564–eligible clear-cell RCC while treating MRD-positive participants with pembrolizumab¹¹⁴.	Recruiting, nonrandomized phase 2; no efficacy results¹⁴.
STRIKE, NCT06661720	Phase 3 test of adding tivozanib to adjuvant pembrolizumab for high-risk RCC¹⁴¹⁵.	Registry-posted trial; no efficacy results¹⁴.

Toxicity

The table preserves regimen-level safety outcomes and limits named-toxicity rows to events reported in more than 5% of patients at any grade; named events with a grade 3 or higher signal are preferred². LITESPARK-022 evaluates belzutifan added to pembrolizumab, not either regimen against surveillance⁵.

Regimen and comparator	Trial-level safety outcomes	Selected named toxicities	Counseling focus
Pembrolizumab versus placebo, KEYNOTE-564	At 30.1 months, grade ≥3 AEs of any cause: 32% versus 18%; immune-mediated AEs: 36% versus 7%; discontinuation due to AEs: 21% versus 2%².	Hypothyroidism: 21% versus 4%; hyperthyroidism: 13% versus 0%². Grade-specific rates for these thyroid events were not reported in the available trial text².	Check thyroid function and review new fatigue, weight or temperature intolerance, and palpitations²¹⁸. Immune toxicity can require a treatment hold, systemic corticosteroids, or hormone replacement; endocrine effects can persist²¹⁸.
Pembrolizumab plus belzutifan versus pembrolizumab plus placebo, LITESPARK-022	Grade ≥3 treatment-emergent AEs: 52.1% versus 30.2%; discontinuation of all study treatment: 11.9% versus 9.0%; immune-mediated AEs or infusion reactions: 35.4% versus 38.7%⁵.	US label: decreased hemoglobin, 95% with grade 3–4 11% (versus 26% and 0.7%); increased ALT, 57% with grade 3–4 13% (versus 33% and 3.2%); hypoxia, 7% with grade ≥3 5%¹⁹.	Monitor CBC, ALT, and oxygen saturation¹⁹. Promptly report new fatigue, lightheadedness, or dyspnea; marked breathing difficulty needs urgent assessment¹⁹.

On-treatment monitoring

SOC/option regimen	Hallmark monitoring toxicity and published rate	Patient action / clinic response
Pembrolizumab	KEYNOTE-564: immune-mediated AEs 36% vs 7%; hypothyroidism 21% vs 4% and hyperthyroidism 13% vs 0%².	Check thyroid function and review fatigue, weight or temperature intolerance, palpitations, and other bowel, lung, liver, skin, or endocrine symptoms; persistent diarrhea, dyspnea, jaundice, or marked fatigue requires prompt contact²¹⁸.
Pembrolizumab plus belzutifan	LITESPARK-022 label versus pembrolizumab plus placebo: decreased hemoglobin 95% vs 26%, grade 3–4 11% vs 0.7%; increased ALT 57% vs 33%, grade 3–4 13% vs 3.2%; hypoxia 7% (grade ≥3 5%) in the combination arm—comparator hypoxia rate not reported in the retained label row¹⁹.	Monitor CBC, ALT, and oxygen saturation; new fatigue, lightheadedness, or dyspnea needs prompt contact and marked breathing difficulty needs urgent assessment¹⁹.

Patient counseling and action plan

For pembrolizumab, ask patients to contact the oncology team for new thyroid symptoms, including unexplained fatigue, weight or temperature intolerance, or palpitations²¹⁸. Immune toxicity can begin during or after treatment and may require a hold, corticosteroids, or hormone replacement; endocrine effects can be lasting²¹⁸.
For pembrolizumab plus belzutifan, monitor CBC, ALT, and oxygen saturation¹⁹. Ask patients to contact the oncology team for new fatigue, lightheadedness, or shortness of breath; marked breathing difficulty needs urgent assessment¹⁹.
For belzutifan, review the label-specific embryo-fetal warning and pregnancy-prevention counseling¹⁹. This clinically critical warning is retained despite not being a numeric trial-toxicity row¹⁹.

Epic phrase

#adjuvantccrcc

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KEYNOTE-564 eligibility

Uses the published trial definition; it does not determine treatment suitability or timing.

Complete calculator fields

Counseling: Reviewed pathology-based recurrence risk after nephrectomy with the KEYNOTE-564 eligibility calculator: Not selected. This calculator classifies the published trial-risk category; it does not replace pathology review or patient-specific treatment assessment.
Counseling: Reviewed adjuvant pembrolizumab and risk-adapted surveillance. In KEYNOTE-564, at 5 years estimated disease-free survival was about 61 in 100 vs 52 in 100 with pembrolizumab versus placebo, and overall survival about 88 in 100 vs 82 in 100 (published 60.9% vs 52.2% DFS; 87.7% vs 82.3% OS). Trial compared pembrolizumab to placebo after surgery, not to surveillance alone. Results apply to the trial population and do not establish benefit in lower-risk or non-clear-cell RCC. US label also permits pembrolizumab plus belzutifan with immature OS versus pembrolizumab alone.
Counseling: Reviewed surveillance and treatment de-escalation: if observation selected, use EAU Leibovich-adapted chest and abdomen CT—low risk (score 0–2) at about 6, 18, and 30 months then every 2 years with option to stop after year 5; intermediate (3–5) at 6, 12, 24, and 36 months then annually then every 2 years after year 5; high (≥6) more frequent early CT including 3 months, then annual after year 3 and every 2 years after year 5. If adjuvant pembrolizumab (± belzutifan), complete up to the labeled year unless toxicity or progression, then continue Leibovich-adapted imaging. Recurrence → metastatic RCC pathway.
Counseling: For M1 NED, reviewed that the trial required complete resection of the primary tumor and a solid, isolated soft-tissue metastasis at nephrectomy or within 1 year. The subgroup was small; multidisciplinary review is needed rather than a standalone efficacy estimate.
Counseling: Reviewed pembrolizumab toxicity in KEYNOTE-564: grade ≥3 AEs of any cause were 32% vs 18% with placebo; 21% vs 2% discontinued because of an AE; immune-mediated AEs occurred in 36% vs 7% with placebo. The named immune toxicities retained for counseling are hypothyroidism (21% vs 4% with placebo) and hyperthyroidism (13% vs 0% with placebo). Some immune effects can occur after treatment and can persist; treatment may require holding therapy, corticosteroids, hormone replacement, or specialist care.
Counseling: Reviewed when to contact oncology promptly: new unexplained fatigue, weight or temperature intolerance, palpitations, lightheadedness, or shortness of breath. Marked breathing difficulty needs urgent assessment. *** after-hours/urgent-assessment instructions reviewed.
Monitoring: With pembrolizumab, obtain thyroid testing and review bowel, lung, liver, skin, and endocrine symptoms. With pembrolizumab plus belzutifan, obtain CBC, ALT, and oxygen saturation; new fatigue, lightheadedness, or dyspnea requires prompt contact. ***
Counseling: If considering pembrolizumab plus belzutifan, reviewed that it is FDA-labeled in the US for eligible clear-cell RCC. LITESPARK-022 showed a DFS benefit versus pembrolizumab plus placebo; overall-survival data were immature. Grade ≥3 treatment-emergent AEs were 52.1% versus 30.2% with pembrolizumab plus placebo. Label-verified safety signals versus pembrolizumab plus placebo are decreased hemoglobin (95% vs 26%; grade 3–4 11% vs 0.7%) and increased ALT (57% vs 33%; grade 3–4 13% vs 3.2%); hypoxia was 7% (grade ≥3 5%) in the combination arm—comparator hypoxia rate was not reported in the retained label row. It is not presented as proven to improve overall survival.
Decision: *** elects pembrolizumab / pembrolizumab plus belzutifan / risk-adapted surveillance / clinical-trial evaluation after shared decision-making.
Labs/NGS: Documented KEYNOTE-564 risk assessment: Not selected; confirmed histology * and risk features *. Obtain thyroid testing for pembrolizumab and CBC, ALT, and oxygen saturation for pembrolizumab plus belzutifan per label and institutional protocol. Severe anemia or hypoxia may require a dose hold, reduction, or discontinuation. Review belzutifan pregnancy-prevention counseling per label. Tumor NGS and ctDNA are not required to select adjuvant therapy.
Procedures: *** postoperative restaging and multidisciplinary review completed / planned. For non-clear-cell histology or disease outside KEYNOTE-564 criteria, favor surveillance or clinical-trial review rather than extrapolating pembrolizumab benefit.
Medications: If selected, pembrolizumab monotherapy is 200 mg IV every 3 weeks for up to 17 cycles. Pembrolizumab plus belzutifan is pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks plus belzutifan 120 mg orally daily, for up to 1 year; confirm current FDA label and local formulary.
Referrals: *** medical oncology / endocrinology / nephrology / clinical-trial consultation, as indicated.
Follow-up: *** risk-adapted chest and abdominal surveillance; review new immune-related symptoms and renal function at each visit.

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Guideline references

Source	Setting-level reference
EAU Renal Cell Carcinoma guideline	Strong recommendation to offer adjuvant pembrolizumab after restaging, preferably 12–16 weeks post-nephrectomy, for KEYNOTE-564-defined clear-cell risk; shared decision-making should address overtreatment, immune toxicity, and discordant ICI trials.
NCCN Kidney Cancer guideline	Current US professional guideline reference for adjuvant systemic-therapy pathways.
ESMO RCC Clinical Practice Guideline	Current European guideline reference for diagnosis, treatment, and follow-up.
AUA localized renal mass guideline	US urology reference for localized-RCC management and follow-up.
FDA Keytruda label, revised July 2026	US labeled adjuvant pembrolizumab monotherapy and pembrolizumab–belzutifan indications and dosing.

Sources

Changelog

2026-09-22: Replaced surveillance with EAU Leibovich-adapted chest/abdomen CT schedule; expanded Biomarkers to five-column clinic/investigational table; mirrored Leibovich cadence in paired dotphrase.
2026-09-22: Renamed Upcoming trial results to Upcoming research; reframed for ongoing trials and field direction.
2026-09-22: Named comparator arms in Standard options / monitoring counseling rates and mirrored comparator-named toxicity counseling in the paired dotphrase.
2026-09-22: Added line-level source superscripts ([^n]) linked to numbered Sources.
2026-09-22: Added Surveillance and treatment de-escalation section; strengthened quantified benefit counseling in dotphrase.

2026-09-21: Added a dedicated all-regimen on-treatment monitoring table for pembrolizumab and pembrolizumab–belzutifan.
2026-09-21: Tightened named-toxicity reporting and paired counseling to a >5% any-grade filter, prioritizing events with a grade ≥3 signal; retained trial-level grade ≥3, immune-mediated, and discontinuation outcomes. Added label-verified decreased hemoglobin, ALT, and hypoxia rates for pembrolizumab–belzutifan.
2026-09-21: Removed calculated risk-reduction and treatment-number metrics from the cross-trial comparison, removed nonstructural emphasis, and condensed Toxicity to a single trial-first table with short counseling; dropped nonessential real-world cohorts and detailed named-toxicity tables.
2026-09-21: Replaced the mixed landmark table with an OpenEvidence-style cross-trial comparison that makes population, regimen, comparator, endpoint, outcome, and generalizability differences explicit.
2026-09-21: Rebuilt around explicit KEYNOTE-564 eligibility, trial-versus-guideline timing, linked primary sources, current FDA-labeled pembrolizumab–belzutifan positioning, named upcoming trial results, and a complete paired counseling phrase.
2026-09-21: Renamed the prospective-evidence section to Upcoming trial results.
2026-09-21: Replaced landmark-only survival display with full source-recreated DFS/OS KM traces, explicitly labeling visual digitization as approximate and keeping later five-year estimates separate.
2026-09-21: Moved and expanded Toxicity to the page bottom; separated trial endpoint/timepoint labels, added regimen-specific anemia/hypoxia and immune-toxicity counseling, and added same-setting real-world pembrolizumab context. Repositioned KM landmark values into dedicated rows to prevent label overlap.

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