10.4 Prognostic Indicators & Site-Specific Data Items (SSDIs): HPV, KRAS, HER2 and More
Key Takeaways
A prognostic factor predicts outcome regardless of treatment (for example, stage or Breslow thickness); a predictive factor predicts benefit from a specific therapy (for example, HER2 for trastuzumab, or RAS mutation for lack of benefit from anti-EGFR antibodies).
HPV-mediated (p16-positive) oropharyngeal cancer has its own AJCC 8th edition staging because of its much better prognosis than p16-negative disease.
ER Summary [3827] is coded 0 (negative, less than 1%), 1 (positive), 7 (test ordered, results not in chart) or 9 (not documented or unknown); PR Summary is [3915] and HER2 Overall Summary is [3855].
Breslow Tumor Thickness [3817] is recorded in millimeters to the nearest tenth (for example, 0.8), and in situ melanoma is coded XX.9.
Tumor Deposits [3934] is coded 00 for none, 01–99 for the exact number, X1 for 100 or more, and X2 when deposits are present but the number is unknown.
Prognostic versus predictive
| Type | Definition | Examples |
|---|---|---|
| Prognostic | Predicts the likely course of disease, independent of treatment | Stage, grade, Breslow thickness, lymphovascular invasion, Ki-67, cytogenetic risk group |
| Predictive | Predicts benefit (or lack of benefit) from a specific treatment | ER/PR (endocrine therapy), HER2 (HER2-targeted drugs), KRAS/NRAS (anti-EGFR antibodies), EGFR/ALK/ROS1 (tyrosine kinase inhibitors), PD-L1 and MSI-H (immunotherapy) |
| Both | Many markers are both | HER2, MSI-H/dMMR, BRAF V600E |
The markers named in the ODS outline
HPV (human papillomavirus)
- Where: oropharynx (tonsil, base of tongue), cervix, anus, vulva, vagina, penis.
- Testing: p16 IHC is the usual surrogate for high-risk HPV in the oropharynx; HPV DNA or RNA testing confirms it.
- Why it matters: AJCC 8th edition stages HPV-mediated (p16+) oropharyngeal cancer in a separate chapter from p16-negative disease, because HPV-related tumors have much better survival. The staging schema, and therefore the SSDIs and stage group, depend on this result.
KRAS (and NRAS, BRAF)
- Where: colorectal, lung and pancreatic cancer.
- Why it matters: in metastatic colorectal cancer, RAS-mutated tumors (KRAS or NRAS) do not benefit from anti-EGFR antibodies (cetuximab, panitumumab), which makes KRAS a predictive marker. BRAF V600E in colorectal cancer carries a poor prognosis. In lung cancer, KRAS G12C has its own targeted drugs.
HER-2 (ERBB2)
- Where: breast and gastric/GE junction cancer, among others.
- Testing: IHC (0, 1+, 2+, 3+) with reflex in situ hybridization for 2+ results (see Section 10.3).
- Why it matters: HER2-positive tumors are more aggressive untreated but respond to HER2-targeted therapy (trastuzumab, pertuzumab, antibody-drug conjugates). In breast cancer, HER2 status is required to assign the AJCC prognostic stage group.
Other high-yield indicators
| Site | Indicators |
|---|---|
| Breast | ER, PR, HER2, grade, multigene signatures (21-gene recurrence score; RS below 11 places some T1–T2 N0 ER+ HER2− tumors in prognostic stage IA), Ki-67 |
| Colorectal | MSI/MMR, KRAS, NRAS, BRAF, CEA, tumor deposits, circumferential resection margin, perineural invasion |
| Lung | EGFR, ALK, ROS1, BRAF, KRAS G12C, PD-L1, separate tumor nodules, visceral pleural invasion |
| Prostate | PSA, Gleason patterns and score, Grade Group, number of positive cores |
| Melanoma | Breslow thickness, ulceration, mitotic rate, LDH |
| Testis | Serum AFP, beta-hCG and LDH (the AJCC S category) |
| CNS | IDH mutation, 1p/19q codeletion, MGMT methylation |
| Myeloma and leukemia | Cytogenetic risk, for example del(17p) and t(4;14) in myeloma, or FLT3 and NPM1 in AML |
Site-Specific Data Items (SSDIs)
SSDIs are defined in the NAACCR Site-Specific Data Item Manual. They took effect for 2018 diagnoses, replacing the Collaborative Stage site-specific factors. Each SSDI belongs to one or more schemas. The registry software derives the schema from the primary site, histology, and sometimes a schema discriminator, and then displays only the SSDIs that apply.
Codes use consistent conventions: actual values or categories, plus special codes. X8 (or XX.8) means not applicable, meaning the information is not collected for this schema, and it will fail edits if a standard setter requires the item. X9 (or XX.9) means not documented or unknown. Always use the SSDI Manual definitions for each item.
Verified SSDI examples
| SSDI | Codes |
|---|---|
| Estrogen Receptor Summary [3827] | 0 = ER negative (0.0% or less than 1%); 1 = ER positive; 7 = test ordered, results not in chart; 9 = not documented, cannot be determined, or unknown if assessed |
| Progesterone Receptor Summary [3915] and HER2 Overall Summary [3855] | Summary interpretations that feed the AJCC breast prognostic stage |
| Breslow Tumor Thickness [3817] | Millimeters to the nearest tenth: 0.0 = no mass or tumor found; 0.1 = more than 0.0 and up to 0.1 mm; 0.2–99.9 = the measurement; XX.1 = 100 mm or larger; A0.1–A9.9 = stated as "at least" that value; AX.0 = stated as greater than 9.9 mm; XX.8 = not applicable; XX.9 = not documented, microinvasion without a depth, in situ melanoma, or unknown |
| Tumor Deposits [3934] (colorectal) | 00 = none; 01–99 = exact number; X1 = 100 or more; X2 = present, number unknown; X8 = not applicable; X9 = not documented, not assessed, or no resection |
Worked example: the pathology report says "Breslow depth 0.75 mm, ulceration present." AJCC melanoma thickness is measured to the nearest 0.1 mm, so 0.75 mm rounds to 0.8 mm. Breslow Tumor Thickness is coded 0.8, and Ulceration is coded as present. The resulting T category is T1b, since a tumor 0.8–1.0 mm, or under 0.8 mm with ulceration, is T1b.
"Data items required by standard setters"
Every NAACCR item has a required status for each standard setter (CoC, SEER, NPCR and the Canadian Council of Cancer Registries). For example, the NAACCR SSDI pages list ER Summary [3827] as "Required, site specific" for NPCR, CoC and SEER. Tumor Deposits [3934] is required by CoC and SEER, with no NPCR recommendation. Key points:
- STORE defines what CoC programs must collect and submit to the NCDB. The SEER manual and NPCR requirements define what central registries collect, and state rules may add items.
- An item "required" by a standard setter must be coded, with unknown codes used only when the information truly is not available. An "X8, not applicable" code in a required field fails edits.
- Dates: NAACCR transmits dates as CCYYMMDD, and the unknown parts are left blank. For example, June 2026 with an unknown day is transmitted as 202606 followed by blanks. The 99 and 99999999 convention belonged to the pre-2010 traditional format. Date flag items explain why a date is blank (for example, no information, or not applicable).
In metastatic colorectal cancer, why is KRAS mutation status considered a predictive marker?
A KRAS mutation proves the tumor arose from an adenomatous polyp.
RAS-mutated tumors do not benefit from anti-EGFR monoclonal antibodies such as cetuximab and panitumumab.
KRAS mutation determines the AJCC T category of colon cancer.
KRAS mutation indicates Lynch syndrome.
A breast pathology report states "ER: positive, 95% of nuclei, strong intensity." How is Estrogen Receptor Summary [3827] coded?
1
95
10
9
A cutaneous melanoma is reported as "melanoma in situ, no invasive component." How is Breslow Tumor Thickness [3817] coded?
0.0
0.1
XX.8
XX.9
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