SEER Inquiry System - Search

The SEER Manual seems to give somewhat conflicting instructions for clinical trial therapies under the Neoadjuvant Therapy data item. One section states that limited systemic therapy may occur in clinical trials to impact the biology of a cancer, but is not a full course of neoadjuvant therapy with the intent to impact extent of surgical resection or other outcomes (organ preservation, function or quality of life); do not code as neoadjuvant therapy for the purposes of this data item. Then another section states for purposes of this data item, the criteria for neoadjuvant therapy include that treatment must follow recommended guidelines for the type and duration of treatment for that particular cancer site and/or histology, and that neoadjuvant therapy may be given as part of a clinical trial.

For example, a patient was diagnosed with invasive ductal carcinoma of the breast, 6 cm in size; treatment planning conference recommended neoadjuvant chemotherapy. The patient elected to participate in a clinical trial and was assigned to a group given the antibody drug conjugate datopotamab deruxtecan (Dato-DXd) plus durvalumab for 12 weeks. There was no physician documentation of intent or expected outcomes, nor yC staging or statement of clinical response. Post-therapy imaging showed no residual mass, and post-therapy mastectomy path report showed only residual ductal carcinoma in situ, stating "Treatment Effect (after neoadjuvant): Residual Cancer Burden - pCR, In the breast - complete response."  The medical oncologist stated post-therapy stage was ypTis ypN0 cM0.

The trial drugs this patient were given do not appear to be approved or standard neoadjuvant/pre-operative drugs in SEER*Rx or NCCN guidelines for this type of cancer; however, the duration of treatment was fairly substantial, and although we don't have clear documentation from physicians as recommended in the SEER manual (which is usually not stated, in our experience), it seems like they may be considering it as neoadjuvant therapy. How should the Neoadjuvant Therapy data item be coded for cases like this? What is the best way to differentiate between clinical trial therapies that are "limited systemic exposure" (code 3) versus true neoadjuvant therapy (code 1)?

Example: Patient has a 04/2023 diagnosis of symptomatic anemia not responsive to Retacrit. Further testing includes diagnostic bone marrow biopsy 10/2023 proving MDS with low blasts and SF3B1 mutation, treated with Relozyl (Luspatercept).

There is no SEER*Rx listing for Reblozyl or Luspatercept. Per web search, Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes.

Is this non-cancer directed treatment since it is given to address the anemia rather than the MDS? If cancer-directed treatment, how should it be coded?

The race category in some hospital electronic medical record systems includes a combined category of “Native Hawaiian/Pacific Islander.” What race code should be used in a situation where the only available information is “Native Hawaiian/Pacific Islander?”

Example: Patient had a 2023 nasopharyngeal mass biopsy showing “Nasopharyngeal non-keratinizing squamous cell carcinoma, undifferentiated type.” 

The Head and Neck Solid Tumor Rules (STRs) do not include an H Rule that instructs us how to code histology when there are two subtypes/variants present for a head and neck primary, nor does the STR define undifferentiated carcinoma as a subtype/variant for 8072.

The WHO Classification of Head and Neck Tumors states non-keratinizing nasopharyngeal carcinoma (non-keratinizing squamous cell carcinoma (SCC) is the most common subtype for nasopharyngeal ca, but that non-keratinizing can be subdivided into undifferentiated and differentiated subtypes.

Should histology be 8020 (undifferentiated carcinoma) or 8072 (non-keratinizing SCC)?

The Solid Tumor Rules state that for cases diagnosed in 2022 and forward, p16 testing CAN be used to assign histology code 8085 (squamous cell carcinoma, HPV positive). The rules also state that for cases diagnosed prior to 1/1/2022, code 8085 MUST be based on ISH testing and not p16. ISH testing is not specifically addressed for 2022+ cases, but are we correct in assuming it can still be used as the basis for 8085?

Multiple CAnswer Forum posts and the AJCC 8th edition Head and Neck staging webinar indicate that the correct chapter/registry staging schema in this situation is determined ONLY by p16 results - not ISH testing, and therefore the Schema Discriminator 2 SSDI should be coded as 1 – p16 negative, regardless of ISH results.

While we understand that histology codes should not be changed based on staging criteria, there is a SEER/NAACCR edit, “Schema Discriminator 2, Head and Neck, Histology (NAACCR)” tag number N6802, that will not allow coding 8085 if Schema Discriminator 2 is coded as 1 (p16 negative). The edit does seem to be correctly enforcing the AJCC guidelines for choosing the staging schema, based on the sources noted above. Do the Solid Tumor or Site-Specific Data Items (SSDI) guidelines need to be modified for this situation?

Example: Patient has a 2023 brain MRI described as having a “new dural based nodule, statistically meningioma, along the left distal tentorial incisura.” All subsequent chart information is related to patient’s unrelated diagnosis of multiple sclerosis only.

Is the terminology “statistically” reportable ambiguous terminology in this context?

We included this histology in SEER Workshop Case 12 and the histology coding accuracy was less than 40%. From emails we received, it is clear that registrars are unaware that the "somatic type malignancy" can vary but code 9084 applies when the diagnosis is teratoma WITH any non-germ cell tumor component. It may be helpful to add a definition for "teratoma with somatic-type malignancy" (9084) to the Solid Tumor Manual.

Note 1 states that this histology is treatment-related neuroendocrine prostatic carcinoma demonstrating complete neuroendocrine differentiation or partial neuroendocrine differentiation with adenocarcinoma after androgen-deprivation therapy (ADT). Conversely, Note 2 says to code 8574/3 only when there is no history of previous prostate adenocarcinoma or history of androgen-deprivation therapy.

The WHO Blue Book does confirm this is a treatment-related histology, so it seems we would only use this for an adenocarcinoma with neuroendocrine differentiation (or even possibly a mixed histology tumor with adenocarcinoma and small cell carcinoma components) if the patient had previous treatment.

If this histology is treatment-related, why would we use this code for a patient without a history of prostate adenocarcinoma or androgen-deprivation therapy? Should Note 2 be corrected?

Does this histology apply to a post-treatment diagnosis of mixed adenocarcinoma and small cell carcinoma? If yes, should this clarification be added?

The patient underwent a gross total resection of the 2005 glioblastoma multiforme (9440/3). The patient was subsequently diagnosed with a 2024 diagnosis of astrocytoma, IDH-mutant, WHO grade 4 (9445/3).

Should Rule M13 apply to the new 2024 diagnosis and a new primary be accessioned because astrocytoma, IDH-mutant, WHO grade 4 is listed on a different row than glioblastoma? It is unclear whether histology 9445 should be classified as being on a different row because it is also listed as a subtype/variant for glioblastoma in Table 3. Table 3 lists histology 9445 as both “Astrocytoma, IDH-mutant, WHO grade 4” and as “Glioblastoma IDH-mutant.”