What approach should be taken for neoadjuvant (pre-surgical) therapy in elderly patients with resectable tumors and impaired renal function?

Neoadjuvant Therapy in Elderly Patients: A Cautious Approach

Neoadjuvant chemotherapy in elderly patients with resectable tumors should generally be avoided in favor of immediate surgery followed by adjuvant therapy, particularly in those over 75 years, as limited data suggest increased postoperative complications without clear survival benefit, and this risk is compounded by impaired renal function requiring dose modifications. 1

Evidence Against Neoadjuvant Therapy in the Elderly

Increased Postoperative Complications

• Elderly patients (≥75 years) treated with neoadjuvant chemotherapy experience significantly higher incidence and severity of postoperative complications compared to younger patients, with no difference in postoperative mortality. 1
• The risk-benefit ratio has not been adequately studied in patients over 80 years of age, and extrapolation from highly selected trial populations to the general elderly population should be made with extreme caution. 1

Lack of Demonstrated Benefit

• Randomized trials do not support the use of neoadjuvant chemotherapy over immediate surgery followed by adjuvant chemotherapy in the general NSCLC population, and this applies even more strongly to elderly patients. 1
• Recent evidence from esophageal adenocarcinoma shows elderly patients experience survival benefit equaling only the length of neoadjuvant treatment itself, while younger patients gain substantial additional survival time. 2

Critical Considerations with Impaired Renal Function

Dose Adjustment Requirements

• Because renal function is often decreased in the elderly, renal function must be considered in carboplatin dosage selection, with creatinine clearance calculation mandatory to reduce systemic toxicity. 3, 4
• Elderly patients with impaired kidney function require appropriately reduced initial carboplatin doses, with careful blood count monitoring between courses. 3
• For patients with uncontrolled diabetes and renal impairment, carboplatin should be reduced to AUC = 4 to minimize myelosuppression risk. 5

Increased Toxicity Risk

• Elderly patients treated with carboplatin are more likely to develop severe thrombocytopenia than younger patients. 3
• Concomitant treatment with aminoglycosides (common in elderly with infections) results in increased renal and/or audiologic toxicity. 3
• More elderly patients require dose reduction or termination of neoadjuvant treatment (40.4% vs 12.4% in younger patients). 2

When Neoadjuvant Therapy Might Be Considered

Highly Selected Scenarios Only

• Neoadjuvant therapy might be prescribed for older patients who are deemed borderline for curative surgery and would benefit from tumor downstaging. 6
• Consider only in fit elderly patients with robust functional status, life expectancy >2 years, and adequate renal function (creatinine clearance allowing standard dosing). 4, 6

Predictors of Treatment Completion Failure

• Failure to complete neoadjuvant therapy and eventual resection is associated with borderline-resectable stage, increased post-treatment CA19-9, and Charlson Comorbidity Index ≥6, but notably NOT with older age alone. 7
• However, elderly patients with these risk factors should proceed directly to surgery when feasible. 7

Recommended Approach: Surgery-First Strategy

Primary Recommendation

• Elderly patients with resectable tumors and impaired renal function should undergo immediate surgical resection at high-volume centers, with adjuvant chemotherapy considered postoperatively based on pathologic findings and recovery status. 1
• Surgical treatment should not be denied to elderly patients based on chronological age alone; decisions should incorporate functional status, comorbidities, and life expectancy. 1

Adjuvant Therapy Advantage

• Adjuvant chemotherapy is associated with survival benefit in the elderly and should not be denied, with tolerability similar to younger patients (<70 years). 1
• The adjuvant approach allows for pathologic staging to guide treatment intensity and permits assessment of surgical recovery before initiating systemic therapy. 1

Common Pitfalls to Avoid

• Do not use age alone as a criterion for denying treatment; functional status predicts chemotherapy toxicity and mortality better than chronological age. 4
• Avoid assuming elderly patients cannot tolerate any chemotherapy—the issue is timing and sequencing, not absolute contraindication. 6, 8
• Do not extrapolate data from highly selected trial populations to frail elderly patients with multiple comorbidities. 1
• Never administer carboplatin without calculating creatinine clearance in elderly patients, as standard dosing may cause severe toxicity with impaired renal function. 3