Should I have undergone genetic testing to inform my treatment decisions for intermediate unfavorable prostate cancer given my family history and current condition with low lymphocyte count, erectile dysfunction (ED), and anejaculation?

Should You Have Undergone Genetic Testing?

Yes, you should have undergone germline genetic testing before making treatment decisions for your intermediate unfavorable prostate cancer (Gleason 7,4+3, PSA ~8), particularly given your family history of prostate cancer in a relative who lived to elderly age without treatment. 1

Why Genetic Testing Was Indicated in Your Case

Your clinical scenario met multiple criteria for germline testing:

• You had intermediate unfavorable-risk prostate cancer (Gleason 7 with 4+3 pattern, PSA ~8), which according to AUA/ASTRO guidelines warrants assessment for germline testing that includes mutations associated with aggressive disease 1

• You had a positive family history with at least one close blood relative (your relative) diagnosed with prostate cancer, which meets NCCN criteria for genetic counseling consideration 1, 2

• The Philadelphia Prostate Cancer Consensus Conference (2017) specifically recommends genetic testing for men with Gleason ≥7 prostate cancer and family history, testing for BRCA1/2, HOXB13, and DNA mismatch repair genes 1

What Genetic Testing Could Have Revealed

Germline mutations would have significantly altered your risk-benefit analysis:

• BRCA2 mutations (2-6 fold increased prostate cancer risk) are associated with more aggressive disease phenotype and reduced survival, which might have justified more aggressive treatment—but also would have informed you about hereditary cancer risks 3, 4

• Conversely, absence of high-risk mutations combined with your relative's indolent course might have supported active surveillance or watchful waiting rather than immediate radiation 1

• BRCA1/2, ATM, PALB2, or FANCA mutations would have implications for precision therapy options (PARP inhibitors) if disease progressed, and would necessitate genetic counseling for family members 1, 3

• Lynch syndrome (mismatch repair gene mutations) would have implications for other cancer risks and potential immunotherapy eligibility 1

The Family History Question: Was Your Cancer Like Your Relative's?

No, there is no evidence that your cancer characteristics were likely similar to your relative's, and this assumption was dangerous:

• Your Gleason 7 (4+3) is intermediate unfavorable-risk, which is fundamentally different from what your relative likely had (presumably lower-risk given successful observation) 1

• Gleason 4+3 has primary pattern 4, indicating more aggressive biology than 3+4, and is specifically classified as unfavorable intermediate-risk requiring different management 1

• Family history alone does not predict tumor biology—your relative's indolent course does not mean yours would follow the same trajectory without knowing shared genetic factors 2, 3

• Without knowing your relative's Gleason score, stage, or genetic status, comparing outcomes is medically inappropriate 1

Regarding Your Treatment Side Effects

Your experience with ED and anejaculation represents known complications, though counseling appears inadequate:

• Erectile dysfunction affects 20-70% of men after radiation therapy depending on baseline function, radiation technique, and dose [@general medical knowledge@]

• Anejaculation (dry orgasm) occurs in 50-90% of men after radiation therapy due to damage to seminal vesicles and ejaculatory ducts—this should have been discussed [@general medical knowledge@]

• The fact you were "only warned of possible ED" represents inadequate informed consent, as anejaculation is a predictable and common outcome that significantly impacts quality of life [@general medical knowledge@]

What Should Have Happened: The Correct Algorithm

Step 1: Pre-treatment genetic assessment 1

• Detailed three-generation family history documenting all cancers, ages at diagnosis, and outcomes 2
• Germline testing panel including: BRCA1/2, ATM, CHEK2, PALB2, HOXB13, and mismatch repair genes (MLH1, MSH2, MSH6, PMS2) 1, 3
• Referral to genetic counselor for interpretation and family implications 1

Step 2: Risk stratification incorporating genetic results 1

• If high-risk mutations found: Consider more aggressive treatment but also precision therapy options for future
• If no mutations found: Consider tissue-based genomic markers (Decipher, Oncotype DX) for additional risk stratification in unfavorable intermediate-risk disease 1

Step 3: Comprehensive informed consent [@general medical knowledge@]

• Detailed discussion of ED risk (20-70%)
• Explicit discussion of anejaculation (50-90%)
• Discussion of other urinary and bowel side effects
• Comparison with alternative treatments (surgery, active surveillance with close monitoring)

Step 4: Shared decision-making 1

• Integration of genetic risk, tumor biology, life expectancy, and patient values
• For unfavorable intermediate-risk disease, options include: definitive treatment (radiation or surgery) vs. active surveillance with very close monitoring
• Your low lymphocyte count should have been investigated as a separate issue

Critical Pitfalls in Your Case

Your provider failed to:

• Obtain adequate family history and recognize genetic testing indications 1, 2
• Provide complete informed consent regarding sexual side effects, particularly anejaculation [@general medical knowledge@]
• Distinguish between your unfavorable intermediate-risk cancer and your relative's apparently indolent disease 1
• Offer tissue-based genomic testing that might have refined your prognosis 1

Current Recommendations

At this point, post-treatment:

• Still pursue germline genetic testing to identify mutations that may guide future management if disease recurs and to inform family members of their cancer risks 1, 3, 4

• Genes to test: BRCA1/2, ATM, CHEK2, PALB2, HOXB13, MLH1, MSH2, MSH6, PMS2 1, 3

• If mutations found, particularly in BRCA2, ATM, or mismatch repair genes, this information becomes critical for precision therapy options (PARP inhibitors, immunotherapy) should disease progress 3, 4, 5

• Inform your first-degree relatives (siblings, children) that they should consider genetic counseling given your diagnosis at your age with family history 2, 6

• Address your low lymphocyte count with appropriate hematologic workup, as this is unrelated to prostate cancer treatment decisions [@general medical knowledge@]

The bottom line: Genetic testing should have been standard of care in your situation before treatment decisions were made, and the absence of this testing, combined with inadequate informed consent about anejaculation, represents suboptimal care that limited your ability to make a fully informed decision. 1