The first 60 days: Cancer of unknown primary (CUP)
Cancer found already spread, where doctors cannot find where it started. Genomic profiling finds a drug target in about a third of cases and tumour-agnostic approvals apply directly; the rest still rely on general-purpose chemotherapy, which is what those tests are changing. Below, week by week, is what OnCo's record of Cancer of unknown primary (CUP) says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Unfavourable, first line, Molecularly directed.
- SurgeonNamed in the standard of care for: Favourable subsets.
- Medical oncologistNamed in the standard of care for: Favourable subsets, Unfavourable, first line, Molecularly directed.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Favourable subsets.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Treat as the presumed primary: e.g. axillary node-only adenocarcinoma in women as breast cancer (mastectomy or axillary dissection + radiotherapy, systemic therapy); cervical node SCC with chemoradiation; peritoneal serous carcinoma as ovarian.
Empiric carboplatin-paclitaxel or cisplatin-gemcitabine ×4-6; comprehensive genomic profiling at diagnosis to find targetable alterations or immunotherapy biomarkers.
Targeted therapy for actionable alterations (e.g. NTRK, BRAF V600E, HER2, ALK) and pembrolizumab for MSI-H/TMB-H; CUPISCO supports molecular-guided therapy after induction chemotherapy.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Immunohistochemistry panel, Comprehensive genomic profiling, MSI, TMB, PD-L1, Tissue-of-origin classifiers, AFP, hCG, PSA, CA-125), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Favourable subsets, Unfavourable: adenocarcinoma with liver/multiple metastases, Poorly differentiated carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Favourable subsets
- For my situation (favourable subsets), which of the standard options do you recommend and why?Guideline options include: Treat as the presumed primary: e.g. axillary node-only adenocarcinoma in women as breast cancer (mastectomy or axillary dissection + radiotherapy, systemic therapy); cervical node SCC with chemoradiation; peritoneal serous carcinoma as ovarian.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Unfavourable, first line
- For my situation (unfavourable, first line), which of the standard options do you recommend and why?Guideline options include: Empiric carboplatin-paclitaxel or cisplatin-gemcitabine ×4-6; comprehensive genomic profiling at diagnosis to find targetable alterations or immunotherapy biomarkers.
- Am I a candidate for Carboplatin, Paclitaxel / nab-paclitaxel, Gemcitabine + cisplatin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Molecularly directed
- For my situation (molecularly directed), which of the standard options do you recommend and why?Guideline options include: Targeted therapy for actionable alterations (e.g. NTRK, BRAF V600E, HER2, ALK) and pembrolizumab for MSI-H/TMB-H; CUPISCO supports molecular-guided therapy after induction chemotherapy.
- Am I a candidate for Pembrolizumab, Nivolumab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Comprehensive genomic profiling, Liquid biopsy (ctDNA), DNA methylation profiling, Pembrolizumab?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether finding the primary matters, or only finding the target”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Median survival under a year for unfavourable CUP despite decades of trials”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Cancer of unknown primary (CUP): the full pageCancer found already spread, where doctors cannot find where it started. Genomic profiling finds a drug target in about a third of cases and tumour-agnostic approvals apply directly; the rest still rely on general-purpose chemotherapy, which is what those tests are changing.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Immunohistochemistry (IHC): Staining a tissue slice with antibodies so a protein shows up in colour under the microscope.
- Tumour mutational burden (TMB): How many mutations a tumour has.
- Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR): Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise.
- Tumour-agnostic (tissue-agnostic) approval: A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
Every term links to the glossary.