What is the best approach to manage an adult patient with stage 3 cancer, considering their overall health and specific cancer type?

Management of Stage 3 Cancer

The management of stage 3 cancer fundamentally depends on the specific cancer type, with stage III non-small cell lung cancer requiring multidisciplinary evaluation and concurrent chemoradiotherapy or multimodality treatment including surgery, while stage III breast cancer typically requires neoadjuvant chemotherapy followed by surgery and radiation, and stage III colorectal cancer requires surgical resection with adjuvant chemotherapy. 1

Critical First Step: Multidisciplinary Team Evaluation

Before initiating any treatment, multidisciplinary discussion must occur involving medical oncology, radiation oncology, and surgical oncology specialists. 1 This is not optional—outcomes data demonstrate that patients treated within a multidisciplinary team framework have significantly better survival (adjusted HR for mortality 0.87; 95% CI, 0.84 to 0.90) compared to those treated outside this structure. 1 The multidisciplinary team should include specialists who devote a significant portion of their clinical practice to the specific cancer type being treated. 1

Stage III Non-Small Cell Lung Cancer (NSCLC)

Initial Staging Workup

• Obtain CT scan of chest and upper abdomen with contrast (unless contraindicated) to exclude metastatic disease. 1
• Perform FDG-PET/CT scan and brain imaging (MRI preferred) to complete staging. 1
• Confirm mediastinal lymph node status by pathologic assessment using endoscopic techniques (EBUS or EUS) as the initial staging modality. 1 If endoscopic staging is unavailable or inconclusive, proceed with surgical confirmation via mediastinoscopy. 1
• Obtain tissue for molecular testing and PD-L1 expression before treatment decisions. 2

Treatment Algorithm Based on Resectability

For Potentially Resectable Stage IIIA (N2) Disease:

Induction therapy followed by surgery may be offered ONLY if ALL of the following conditions are met: 1

• Complete R0 resection of primary tumor and involved lymph nodes is deemed possible
• N3 lymph nodes are confirmed not involved by multidisciplinary consensus
• Perioperative 90-day mortality is expected to be ≤5%
• Treatment should be performed at high-volume centers with specific expertise 1

For patients proceeding with surgical approach: 1, 2

• Administer neoadjuvant chemotherapy (platinum-based doublet) or concurrent chemoradiation before surgery
• Following complete resection, give adjuvant platinum-based chemotherapy for 3-4 cycles starting within 12 weeks of surgery 3
• Consider adjuvant immunotherapy based on PD-L1 expression and molecular profile 2

For Unresectable Stage III (N2, N3) Disease:

Concurrent platinum-based chemoradiotherapy (60-66 Gy) is the standard treatment for patients with performance status 0-1 and minimal weight loss (<10%). 1 This approach provides superior survival compared to radiotherapy alone (Grade 1A recommendation) or sequential chemoradiotherapy (Grade 1A recommendation). 1

Following completion of concurrent chemoradiotherapy without disease progression, administer durvalumab (anti-PD-L1 immunotherapy) as consolidation therapy for up to 12 months. 4 This PACIFIC regimen represents a turning point in stage III NSCLC management, with significantly improved median relapse-free survival (16.3 months) and overall survival (46.5 months) compared to chemoradiotherapy alone. 4

Common Pitfalls to Avoid

• Do not use radiotherapy alone—it is inferior to combined chemoradiotherapy (Grade 1A). 1
• Do not routinely recommend neoadjuvant therapy followed by surgery over definitive chemoradiotherapy, as randomized trials show equivalent overall survival. 1 Surgery adds morbidity without clear survival benefit except in highly selected patients at high-volume centers with low perioperative mortality. 1
• Do not give prophylactic cranial irradiation after concurrent chemoradiotherapy outside of clinical trials (Grade 2C). 1
• For patients with performance status 2 or substantial weight loss (>10%), do not pursue aggressive concurrent chemoradiotherapy. 1 Consider sequential approaches or palliative care.

Stage III Breast Cancer

Operable Locally Advanced Disease (Clinical T3N1M0):

Initiate neoadjuvant chemotherapy with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) or anthracycline-based regimen for 3-4 cycles. 1, 5 After induction chemotherapy, perform total mastectomy with axillary dissection, followed by adjuvant chemotherapy and radiation therapy. 1, 5

Inoperable Stage IIIB Disease:

Begin with combination chemotherapy to achieve tumor response, followed by local treatment (surgery and/or radiotherapy), then continue adjuvant chemotherapy. 5 This multimodality approach rendered 94% of patients disease-free with 5-year survival of 44% for stage IIIB disease. 5

Key Considerations:

• Obtain ER/PR receptor status and HER2 status before initiating chemotherapy. 1
• Younger patients and those with estrogen receptor-positive tumors have better survival outcomes. 5
• Quality of response to induction chemotherapy strongly correlates with prognosis. 5

Stage III Colorectal Cancer

Colon Cancer:

Perform surgical resection (complete colectomy with regional lymphadenectomy) followed by adjuvant platinum-based chemotherapy (FOLFOX or CAPOX regimen). 1 Surgery alone is insufficient—adjuvant chemotherapy is the standard of care for stage III colon cancer. 1

Rectal Cancer:

Treatment strategy divides into: 1

• Preoperative short-course radiotherapy alone, OR
• Preoperative long-course chemoradiotherapy (preferred in Europe)
• Followed by surgical resection with total mesorectal excision
• Then adjuvant chemotherapy

Special Considerations:

• Test for MSI-H/dMMR status immediately, as this fundamentally changes treatment from chemotherapy to immunotherapy (pembrolizumab or nivolumab) in metastatic settings. 6
• Elderly patients (≥65 years) are often inadequately staged and less likely to receive appropriate adjuvant therapy, but age alone should not preclude standard treatment. 1

Performance Status and Patient Selection

Performance status is the single most important factor determining treatment intensity: 1

• PS 0-1 with minimal weight loss (<10%): Pursue aggressive concurrent chemoradiotherapy or multimodality treatment
• PS 2 or weight loss >10%: Consider sequential approaches, dose-reduced regimens, or palliative care 1
• Significant cardiopulmonary comorbidities (COPD, coronary disease) may significantly hamper curative-intent strategies. 1

Monitoring and Supportive Care

Provide preparatory and ongoing support with input from dieticians, palliative care professionals, and respiratory physicians during treatment. 1 This approach improves treatment delivery and allows patients to achieve maximum benefit from their treatments. 1

Limit steroid use during chemoradiotherapy, as steroids may negatively impact subsequent immunotherapy efficacy. 1