From clinical context to a testing pathway
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Results and counselling
Before ordering germline testing
- Explain what can be found: a pathogenic variant, a variant of uncertain significance, or no variant; and what each does and does not mean.
- Discuss implications for relatives, including daughters and sons, and that a positive result may change screening for breast, ovarian, pancreatic and colorectal cancer in the family.
- Record informed consent. Where a genetic counsellor is not available locally, tele-counselling services exist in several Indian centres; confirm availability before drawing blood.
- Confirm the panel scope, sample type, cost to the patient, turnaround, and whether the laboratory reports according to ACMG/AMP classification.
Interpreting the result
| Result | What it means | What it does not mean |
|---|---|---|
| Pathogenic or likely pathogenic | Inherited predisposition confirmed. Offer cascade testing to first-degree relatives; treatment relevance depends on the gene (see Genes & panels). | Not automatically an indication for a PARP inhibitor; benefit is gene-specific and stage-specific. |
| Variant of uncertain significance | Insufficient evidence to classify. Manage the patient and family on clinical and family-history grounds. Ask the laboratory about reclassification policy and re-contact. | Not a positive result. Do not offer cascade testing or change treatment on a VUS. |
| No variant found | Reduces, but does not remove, the probability of inherited risk, and only for the genes covered by that panel. | Not "no hereditary risk". A strong family history still warrants genetics referral. A negative germline result says nothing about somatic (tumour) alterations. |
| Tumour variant in a predisposition gene | May be somatic or germline; germline confirmation is needed for BRCA1/2, MMR genes, ATM, PALB2, CHEK2 and similar. | Not proof of inherited risk until confirmed on a blood or saliva sample. |
Cascade testing
Once a familial variant is known, relatives need testing only for that variant, which is cheaper and faster than a panel. Provide a written copy of the report naming the exact variant (HGVS nomenclature) so relatives can be tested anywhere.
Genes and panels
Two different questions are often mixed together. Inherited predisposition asks which genes explain risk in the patient and family. Treatment biomarkers ask which tumour alterations change therapy. Some genes appear in both lists; many do not.
Germline predisposition panel (blood or saliva)
| Group | Genes | Note |
|---|---|---|
| Homologous recombination repair | BRCA2, BRCA1, ATM, PALB2, CHEK2 | Core of most guideline panels. BRCA2 carries the highest prostate-specific risk and the strongest treatment relevance. |
| Mismatch repair (Lynch) | MLH1, MSH2, MSH6, PMS2 (and EPCAM deletions) | Relevant to colorectal and endometrial risk in the family and to immunotherapy eligibility if the tumour is dMMR. |
| Other prostate-associated | HOXB13, TP53 | HOXB13 raises prostate risk but has no current treatment implication. |
| Extended HRR (often bundled) | RAD51C, RAD51D, BRIP1, BARD1, NBN, FANCA | Weaker prostate-risk evidence; useful mainly for family counselling and trial eligibility. |
Tumour biomarkers (tissue or ctDNA)
| Biomarker | Evidence for treatment benefit | Overseas approval (regulator, date) | India |
|---|---|---|---|
| BRCA2 / BRCA1 (germline or somatic) | Strongest evidence for PARP-inhibitor benefit; BRCA2 stronger than BRCA1. | Olaparib monotherapy after ARPI, FDA May 2020; EU Nov 2020 (BRCA1/2). Olaparib + abiraterone, FDA May 2023. Niraparib + abiraterone, FDA Aug 2023. | Unverified |
| Other HRR (ATM, CHEK2, CDK12, PALB2…) | Limited or inconsistent; PALB2 has case-level support, ATM and CHEK2 largely do not. | Talazoparib + enzalutamide (HRR-mutated), FDA Jun 2023; olaparib monotherapy label covers a wider HRR list in the US than in the EU. | Unverified |
| MSI-high / dMMR | Tumour-agnostic response to PD-1 inhibition; uncommon (2–3%) in prostate cancer. | Pembrolizumab tumour-agnostic, FDA May 2017. | Unverified |
| TMB-high (≥10 mut/Mb) | Weak in prostate cancer; usually overlaps with dMMR. | Pembrolizumab, FDA Jun 2020 (tumour-agnostic). | Unverified |
"Unverified" means this resource has not confirmed CDSCO marketing approval or the approved indication wording in India. Do not infer Indian approval from overseas approval.
NGS for clinicians
Panel versus exome
A targeted panel sequences a defined gene list at high depth and is the standard for both germline and tumour testing. Exome or genome sequencing covers more but at lower depth per gene and with more incidental findings; it is a research or specialist tool, not a routine order.
Tissue versus ctDNA
- Tissue: prefer the most recent metastatic sample; archival prostatectomy or biopsy tissue is acceptable but older blocks fail more often. Ask the laboratory for a tumour-content threshold and a failure rate.
- ctDNA: useful when tissue is unavailable or fails. Sensitivity depends on tumour burden; a negative ctDNA result at low PSA or low volume does not exclude an alteration. Clonal haematopoiesis can produce false-positive ATM and CHEK2 calls in plasma.
- Neither replaces a germline test. Tumour testing can miss germline variants, and a tumour-detected variant needs germline confirmation.
MSI, dMMR and TMB
MSI is measured on DNA; dMMR is measured by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2. Either is acceptable; IHC is cheaper and widely available in India. TMB needs a large panel and calibrated thresholds, and adds little beyond MSI in prostate cancer.
What to check on a report
- Sample type, tumour content, and sequencing depth.
- Genes covered, and whether large deletions or duplications were assessed.
- Variant classification system and the classification of each reported variant.
- Whether the finding is described as somatic, germline, or undetermined.
- Laboratory accreditation (NABL or equivalent) and the report date.
Evidence and versions
Every statement in this app is one of four kinds. The pathway output labels each line accordingly.
Sources used to build the logic
| Source | Version or date | Used for | Status |
|---|---|---|---|
| NCCN Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic and Prostate | v3.2026, 19 Feb 2026 | Germline testing criteria, family-history thresholds, gene list | Version reported in supplied draft; full PDF and wording require reviewer verification |
| NCCN Prostate Cancer | 2026 version — number to confirm | Somatic testing by stage; intraductal/cribriform "consider" criterion | Version number unverified |
| EAU Prostate Cancer Guideline | 2026 edition | Cribriform/intraductal handling; risk-group definitions | Genomics recommendations to be transcribed by a reviewer |
| Xu et al., The Prostate, 2025 | May 2025 | Gene-level differences in PARP-inhibitor evidence | Peer-reviewed analysis, not a guideline |
| PROfound, PROpel, MAGNITUDE, TALAPRO-2 | 2020–2024 | PARP-inhibitor evidence in mCRPC | Trials |
| AMPLITUDE (niraparib + abiraterone, HRR-deficient mHSPC) | Nat Med, Oct 2025 | Emerging evidence in mHSPC | Trial; regulatory status unverified |
| CDSCO / Indian prescribing information | — | Indian approval status of olaparib, talazoparib, niraparib, pembrolizumab | Not yet checked |
No Indian consensus statement is cited because none has been verified for this build. If one exists, add it here with its date.
About this initiative
Dr. Sachin Arakere Nataraj
Founder & Clinical Lead
Uro-Oncology & Robotic Surgery
Prostate Cancer Genomics India is a free educational resource for urologists, uro-oncologists, medical oncologists and other clinicians in India. It was founded and is clinically led by Dr. Sachin Arakere Nataraj.
How this was written
Drafted with AI assistance from published guidelines and trials, then edited by the founder. Its logic is deterministic: the same inputs always produce the same output. Clinical selections and PDF generation are processed on this device.
Review status
| Review | Status |
|---|---|
| Independent clinical geneticist or genetic counsellor | Not yet done |
| Independent medical oncologist | Not yet done |
| Indian regulatory status of named drugs | Not yet checked |
| Clinical scenario validation | Not yet signed off by an independent reviewer |
| Privacy review | Clinical selections stay on the device; formal review not yet done. Hosting providers may process ordinary access logs. |
What this app is not
It does not replace guideline text, laboratory advice or specialist consultation. Pathway outputs are not signed or endorsed by any clinician. Medical-device regulatory classification has not been established; an educational label alone does not determine that classification.
Founder branding · not a clinical sign-off