Previously treated, recurrent, or metastatic vulvar or vaginal squamous cell carcinoma wi...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-VULVAR-VAGINAL-SCC-PDL1-CPS-1-PLUS`
Type	Red flag
Status	reviewed 2026-07-11 \| pending_clinical_signoff
Diseases	`DIS-VULVAR-VAGINAL-SCC`
Sources	`SRC-KEYNOTE-158-VULVAR-SHAPIRA-FROMMER-2022`

Red Flag Origin

Definition	Previously treated, recurrent, or metastatic vulvar or vaginal squamous cell carcinoma with PD-L1 CPS ≥1 by 22C3 IHC. KEYNOTE-158 (Shapira-Frommer, Gynecol Oncol 2022) evaluated pembrolizumab monotherapy in previously treated advanced vulvar SCC (n=101): durable responses (ORR 10.9% overall, median DOR 20.4 months among responders) occurred in BOTH PD-L1-positive (ORR 9.5%, n=84) and PD-L1-negative (ORR 28.6%, n=7 — small subgroup, wide CI) patients. CPS≥1 is therefore NOT a validated hard predictive cutoff for vulvar SCC pembrolizumab response, unlike the CPS≥1 FDA-label requirement for cervical cancer (KEYNOTE-826). This RedFlag surfaces PD-L1 CPS status as an eligibility-informing (not strictly gating) marker for pembrolizumab access in metastatic/recurrent vulvar-vaginal SCC, consistent with cross-tumor pembrolizumab-eligibility practice pending a vulvar/vaginal-specific regulatory...
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-VULVAR-VAGINAL-SCC-1L

Trigger Logic

{
  "any_of": [
    {
      "comparator": ">=",
      "finding": "pdl1_cps",
      "threshold": 1
    },
    {
      "comparator": ">=",
      "finding": "pdl1_cps_22c3",
      "threshold": 1
    },
    {
      "comparator": ">=",
      "finding": "BIO-PDL1-CPS",
      "threshold": 1
    }
  ],
  "type": "biomarker"
}

Notes

Severity set to 'minor' (lower than the analogous RF-CERVICAL-PDL1-CPS-1-PLUS, which is 'major') because the vulvar- SCC evidence base (KEYNOTE-158 basket cohort, n=101, non-randomized) does NOT show a clean PD-L1-positive vs PD-L1-negative response differential — unlike cervical cancer's KEYNOTE-826 randomized CPS≥1 stratification. This RF is authored as directed by the disease narrative ('metastatic — pembrolizumab if PD-L1+') for consistency with cross-tumor pembrolizumab-eligibility conventions in this KB, but the notes above make the evidentiary caveat explicit so a clinical reviewer can recalibrate severity/priority or the ALGO's routing logic. STUB pending clinical co-lead signoff (CHARTER §6.1; dev-mode-exempted per CHARTER §8.3 — draft content only).

Used By

Algorithms

ALGO-VULVAR-VAGINAL-SCC-1L - ALGO-VULVAR-VAGINAL-SCC-1L

Indications

IND-VULVAR-VAGINAL-SCC-METASTATIC-1L-PEMBRO - IND-VULVAR-VAGINAL-SCC-METASTATIC-1L-PEMBRO