Research Library | MONARCH Precision Oncology

Clinical Overviews

Visual reference maps for clinical context. Not for treatment decisions — refer to ESMO/NCCN guidelines.

GYNAECOLOGICAL ONCOLOGY FIGO 2014 · ESMO 2023 · NCCN v2.2024

Ovarian Cancer — Histology, Spread, Biomarkers & Treatment Logic

Epithelial · Germ Cell · Sex Cord Stromal · FIGO I–IV · Debulking · Carboplatin · PARP inhibitors · BRCA1/2

Tumor subtypes

High grade serous

Most common · BRCA1/2, TP53 · Fallopian tube origin · Post-menopausal

BRCA1/2TP53Epithelial · 90%

Low grade serous

Indolent · KRAS / BRAF driven · Better prognosis than HG serous

KRASBRAF

Endometrioid

Endometriosis-related · PTEN mutations · Better prognosis · Lynch syndrome link

PTENLynch

Clear cell

Platinum-resistant · Worst prognosis among epithelial subtypes

Platinum resistant

Mucinous

Large · Unilateral · Pseudomyxoma peritonei · Exclude appendix primary

Unilateral

Germ cell & sex cord

Dysgerminoma (LDH) · Yolk sac (AFP) · Teratoma · Granulosa cell (inhibin B) · Sertoli-Leydig (testosterone)

AFPLDHInhibin B

Key biomarkers

BRCA1/2 — HGS, germline/somatic TP53 — HG serous KRAS / BRAF — LG serous PTEN — endometrioid CA125 >35 U/mL — serous monitoring AFP — yolk sac LDH — dysgerminoma Inhibin B — granulosa cell Testosterone — Sertoli-Leydig

CA125 is not specific — falsely elevated in endometriosis, PID, peritoneal disease. USS/CT + CA125 used together for initial workup.

Spread pattern

Peritoneal deposits

Diaphragm · Bowel · Mesentery studding

Omental cake

Greater omentum replaced by tumour — visible on CT

Nodal spread

Para-aortic (primary drainage) · Pelvic iliac · Obturator (secondary)

Late presentation

Silent killer · 70% present FIGO III · Bloating · Pelvic pain · Early satiety · Urinary frequency

FIGO staging summary

IConfined to ovaries — IA one ovary, IB both, IC capsule rupture / positive washings

IIPelvic extension — IIA uterus/tubes, IIB other pelvic structures

IIIPeritoneal spread beyond pelvis / para-aortic nodes — 70% of cases at diagnosis

IVDistant metastasis — IVA pleural effusion, IVB liver parenchyma / distant nodes

Treatment logic

Debulking surgery

TAH-BSO + omentectomy
<1 cm residual = optimal

→

Carboplatin / paclitaxel

Platinum-based · AUC 5-6 IV
3 weekly × 6 cycles

→

PARP inhibitor maintenance

Olaparib · BRCA mutated
Synthetic lethality

→

± Bevacizumab

Anti-VEGF · Added to chemo
Advanced disease

BRCA testing guides PARP inhibitor eligibility. Neoadjuvant chemotherapy (NACT) used when primary debulking is not feasible — interval debulking after 3 cycles.

References: FIGO 2014 staging · ESMO Clinical Practice Guidelines: Ovarian Cancer 2023 · NCCN Ovarian Cancer v2.2024 · SOLO-1 trial (olaparib maintenance) · ICON7/GOG-0218 (bevacizumab). Not for clinical decision-making.

BREAST ONCOLOGY St Gallen 2023 · ESMO Early BC 2023 · NCCN v4.2024

Breast Cancer — Molecular Subtypes, Biomarkers & Treatment Logic

Luminal A · Luminal B · HER2-enriched · Triple Negative · ER · PR · HER2 · Ki-67 · BRCA1/2 · PD-L1

Four molecular subtypes

Luminal A

ER strong+ · PR+ · HER2− · Ki-67 low
Slow growing · Best prognosis · Highly endocrine-sensitive

ER strong+Ki-67 lowBest Px

Luminal B

ER+ · HER2− or HER2+ · Ki-67 higher
Faster growth · Moderate endocrine sensitivity · Chemo more likely

Ki-67 higherER+HER2 ±

HER2-enriched

ER− · PR− · HER2+ · Ki-67 high
Aggressive · HER2-targeted therapy drives outcomes

HER2+ER− PR−Ki-67 high

Triple negative (TNBC)

ER− · PR− · HER2− · Ki-67 high
Most aggressive · BRCA1 link · Chemo backbone · Immunotherapy in PD-L1+

ER− PR− HER2−BRCA1PD-L1

Luminal A vs Luminal B — key differences

Feature	Luminal A	Luminal B
ER status	Strong positive	Positive
Ki-67	Low (<14–20%)	Higher (≥20%)
Growth rate	Slow	Faster
Prognosis	Better	Worse
Chemo benefit	Often small	More likely
Endocrine sensitivity	Very high	Moderate–high
Recurrence risk	Lower	Higher
Genomic testing utility	May avoid chemo (Oncotype low)	High score → chemo benefit

Ki-67 threshold varies by lab — St Gallen recommends ≥20% as a guide. Oncotype DX / Prosigna used to refine chemo decisions in ER+ HER2− early breast cancer.

Key biomarkers

ER — endocrine sensitivity, luminal subtypes PR — additional endocrine marker HER2 — IHC 3+ or FISH amplified · targeted therapy Ki-67 — proliferation index · luminal A vs B cutoff BRCA1/2 — TNBC, hereditary risk, PARPi eligibility PD-L1 (CPS ≥10) — immunotherapy in TNBC Oncotype DX — RS score, chemo decision in ER+ HER2− PIK3CA — alpelisib eligibility in HR+ HER2−

Treatment logic by subtype

Luminal A & B (ER+ HER2−)

Endocrine therapy

Tamoxifen / AI

± Chemo

Oncotype RS guided

± CDK4/6i

Advanced disease

± Alpelisib

PIK3CA mutant

HER2-enriched (HER2+)

Trastuzumab

Anti-HER2

Pertuzumab

Dual HER2 block

Chemo

Taxane backbone

T-DM1 / T-DXd

Residual disease / 2L

Triple Negative (TNBC)

Chemo

Anthracycline / taxane

± Pembrolizumab

PD-L1+ (CPS ≥10)

± Olaparib

BRCA1/2 mutant

Sacituzumab

Trop-2 ADC · 2L+

References: St Gallen International Expert Consensus 2023 · ESMO Early Breast Cancer Clinical Practice Guidelines 2023 · NCCN Breast Cancer v4.2024 · MONARCH-3 (abemaciclib) · MONALEESA-2 (ribociclib) · KEYNOTE-522 (pembrolizumab TNBC) · OlympiA trial (olaparib adjuvant). Not for clinical decision-making.

GENITOURINARY ONCOLOGY ASCO 2026 · ENZAMET · CHAARTED · STAMPEDE · EAU 2024

Metastatic Prostate Cancer — Decipher Classifier, Volume Stratification & Treatment Selection

mHSPC · ADT · Enzalutamide · Docetaxel · Decipher DGC · ARPI · Triplet vs Doublet · Biomarker-guided intensification

Decipher Prostate Genomic Classifier (DGC) — what it is

What it measures

22-gene RNA expression panel derived from tumour biopsy. Captures biological aggressiveness beyond Gleason grade — proliferation, androgen signalling, immune infiltration, and cell differentiation pathways.

Score range & thresholds

Score 0–1 (continuous):
Low <0.45
Intermediate 0.45–0.60
High >0.60
ENZAMET threshold >0.85

Sample & platform

FFPE prostate biopsy cores (primary tumour). Transcriptome profiling via Veracyte clinical test. Can be performed on diagnostic biopsy — does not require prostatectomy specimen.

Validated uses

• Post-RP adjuvant vs salvage RT decision
• Metastatic risk after RP
• Active surveillance candidacy
• NEW (ENZAMET 2026): Doublet vs triplet selection in mHSPC

ENZAMET 2026 — DGC as predictive biomarker for triplet therapy (Level 1B evidence)

Treatment group	N	5yr OS — DGC ≤0.85	5yr OS — DGC >0.85	aHR (higher vs lower)
ADT + ENZ	178	86% (78–93%)	62% (52–72%)	2.29 (1.3–4.2) ⚠
ADT + ENZ + DOC	142	66% (53–79%)	58% (48–68%)	1.08 (0.6–1.9) ✓
ADT + ENZ (high volume)	55	81% (65–96%)	41% (23–60%)	2.83 (1.1–7.5) ⚠⚠
ADT + ENZ + DOC (high volume)	98	58% (42–75%)	48% (36–61%)	1.07 (0.6–1.9) ✓

p-interaction DGC × docetaxel benefit = 0.043. Overall DGC >0.85 prognostic: aHR 1.37 [1.06–1.78], p=0.02. Median follow-up 5.6 years. N=634. ⚠ = significant OS penalty · ✓ = penalty abolished

mHSPC treatment selection — volume + Decipher framework

DGC ≤0.85 — any volume

No docetaxel benefit demonstrated.
ADT + ARPI doublet appropriate.
Endocrine-sensitive biology.

ADT + ENZADT + ABIDoublet

DGC >0.85 — low volume

Poor prognosis on doublet alone.
Consider triplet — docetaxel benefit likely.
Interaction seen but LV numbers small.

ADT + ENZ + DOCConsider triplet

DGC >0.85 — high volume

Strongest evidence for triplet. 5yr OS 41% on doublet vs 48% with DOC added. aHR 2.83 penalty negated by docetaxel.

ADT + ENZ + DOCTriplet preferred

No Decipher available

Fall back to clinical criteria:
High volume (CHAARTED) → triplet.
Low volume + sync → doublet ARPI.
Fit patient + rapid progression → consider triplet.

Volume-guidedClinical staging

Volume definitions & key trial context

CHAARTED high volume

≥4 bone mets (≥1 beyond pelvis/spine) OR visceral mets. Docetaxel OS benefit established in HV mHSPC.

≥4 bone metsVisceral

STAMPEDE / ENZAMET

Defined synchronous (de novo mHSPC at diagnosis) vs metachronous (progression after localised treatment). Sync associated with higher DGC and poorer baseline OS.

Sync 62%Metach 38%

Decipher in ENZAMET

Median DGC 0.88 (IQR 0.75–0.96). 55% had DGC >0.85. Higher in planned DOC group (62%) vs non-DOC (49%). Reflects biological enrichment in clinically selected high-risk patients.

Median 0.8855% >0.85

Limitations to note

Conference abstract — full peer review pending. Propensity-weighted observational analysis within RCT. LV subgroup underpowered (n=44 DOC). Available in 83% of pts — selection bias possible.

Abstract onlyPrespecified

References: Sweeney et al. ASCO 2026 Abstr #5001 (ENZAMET) · Davis et al. NEJM 2019 (ENZAMET primary) · Sweeney et al. NEJM 2015 (CHAARTED) · James et al. NEJM 2016 (STAMPEDE) · Decipher Prostate (Veracyte) · EAU Prostate Cancer Guidelines 2024 · NCCN Prostate Cancer v2.2025. Not for clinical decision-making.

UROLOGICAL ONCOLOGY PARADIGM · Nature Cancer 2026 · NCT04067713

mCSPC — ctDNA + PSA Liquid Biopsy Monitoring on First-Line Treatment

High-volume mCSPC · ADT + docetaxel or ARPI · ctDNA (PCF_SELECT) · On-treatment risk stratification · Survival prediction

Why ctDNA alongside PSA?

PSA limitations

Regulated by androgen receptor — reflects AR signalling, not overall tumour burden. Nadir takes months to reach; doesn't capture all treatment effects.

AR-dependentSlow kinetics

ctDNA advantages

Not regulated by AR — captures tumour dynamics independently. Detects resistant clones months before radiological progression. Becomes a risk factor before PSA nadir is reached.

AR-independentEarlier signal

How ctDNA is detected (PCF_SELECT)

Targeted NGS panel detecting allelic imbalance at heterozygous SNPs in copy-number-change regions (8p, 16q, PTEN, RB1) — characteristic of advanced prostate cancer, even at low circulating fractions.

Copy numberAllelic imbalance

ctDNA positivity threshold

Pre-specified decision tree: ≥20% tumour fraction (copy number + AI profile), OR ≥3% by allelic imbalance depth in hemizygous deletions, OR ≥1% seen in both methods.

Pre-specifiedCLONETv2

Key survival outcomes — ctDNA at cycles 3/4 (primary timepoint, n=104)

Group	12-mo OS	24-mo OS	36-mo OS	Median OS
ctDNA-negative	99%	85%	68%	Not reached
ctDNA-positive	73%	50%	39%	24 months

Overall HR 3.07 (95% CI 1.64–5.74, p<0.001). Strongest in PARADIGM-D (docetaxel): HR 11.86 (3.71–37.94). ctDNA was the only independent predictor of OS in multivariable analysis including all clinical variables. Median follow-up 41 months.

Combined ctDNA + PSA risk groups (cycles 3/4)

Best prognosis

ctDNA-negative + PSA ≤0.2 ng/mL
Reference group. Near-complete biochemical and molecular remission.

HR = reference

Intermediate

ctDNA-negative + PSA >0.2–4 ng/mL
HR 2.43 (0.55–10.72) — trend but not significant in isolation.

HR ~2.4

High risk

ctDNA-positive + PSA >0.2–4 ng/mL
HR 7.86 (1.63–37.93) — independent of PSA alone.

HR ~7.9

Poorest prognosis

ctDNA-positive + PSA >4 ng/mL
HR 20.34 (4.06–101.90). Adding ctDNA to PSA improved 12-mo AUC from 0.82 → 0.91.

HR 20.34AUC 0.91

Both ctDNA and PSA were independent risk factors in multivariable models (HR 3.63 for ctDNA; HR 5.52 for PSA >0.2). At cycle 1, PSA was NOT independently associated with OS — only ctDNA was (HR 2.46).

ctDNA dynamics with treatment

Before ADT

70% ctDNA-positive. Median fraction 0.22. High tumour burden at baseline.

70% positive

Cycle 1 (ADT started)

37% ctDNA-positive. Median fraction 0.04. Significant decline with ADT (p=0.02). PSA still rarely <0.2 at this point.

37% positive

Cycles 3/4 (primary endpoint)

29% ctDNA-positive. Median fraction 0.03. Persistence on doublet = very poor prognosis. Chosen as earliest actionable timepoint.

29% positiveActionable

Positive at both C1 + C3/4

Median OS only 8.5 months. HR 17.00 (6.64–43.47, p<0.0001) vs those negative at both timepoints.

Median OS 8.5 moHR 17.0

Clinical implications & caveats

What this enables

Early identification of patients at high risk of death during first-line treatment — before imaging shows progression. Supports rationale for ctDNA-guided treatment escalation trials.

Relationship to Decipher

Decipher (tissue) guides treatment selection at baseline. ctDNA (liquid) monitors response once treatment is running. Complementary, not competing tools.

Key caveats

Observational — no randomisation. PARADIGM-D underpowered (n=32). PCF_SELECT assay not yet widely available. No change-of-management data yet.

What comes next

PARADIGM-E (n=75, independent validation cohort, results ~2027). Clinical trials formally testing ctDNA-guided treatment modification in mCSPC are the logical next step.

References: Jayaram et al. Nature Cancer 2026 (PARADIGM, NCT04067713) · Orlando et al. NAR Cancer 2022 (PCF_SELECT) · Harshman et al. JCO 2018 (PSA nadir prognostic) · Gharzai et al. NEJM Evid 2023 (PFS/OS surrogacy). Not for clinical decision-making.

Your curatedresearch collection.

Clinical Overviews

Ovarian Cancer — Histology, Spread, Biomarkers & Treatment Logic

Breast Cancer — Molecular Subtypes, Biomarkers & Treatment Logic

Metastatic Prostate Cancer — Decipher Classifier, Volume Stratification & Treatment Selection

mCSPC — ctDNA + PSA Liquid Biopsy Monitoring on First-Line Treatment

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