Diagnostic Workup and Multidisciplinary Management Approaches

Dr. Strosberg discusses clinical practice approaches when encountering patients like James with colonic masses demonstrating very high Ki-67 indices and neuroendocrine immunohistochemical markers. When pathologists confirm poorly differentiated carcinoma with characteristic Ki-67 exceeding 55% to 70% and appropriate morphology, metastatic disease typically requires medical oncology management with cytotoxic chemotherapy as the primary intervention.

Multidisciplinary therapy roles prove much more robust for well-differentiated neuroendocrine tumors compared to poorly differentiated carcinomas. Limited roles exist for surgical debulking or liver-directed therapies in poorly differentiated disease, with traditional management centering on intravenous platinum-based chemotherapy regimens. Staging uncertainty may warrant FDG-PET imaging, which proves more useful than somatostatin receptor scintigraphy typically showing negative results in poorly differentiated tumors.

Dr. Strosberg addresses common clinical pitfalls when managing patients with extrapulmonary NECs. Practitioners often reflexively consider colorectal cancer regimens for colonic primaries or lung cancer protocols for thoracic presentations. However, extrapulmonary NECs comprise approximately 10% of all poorly differentiated NECs, with lung primaries representing the vast majority including SCLC and fewer large cell variants.

Due to rarity, treatment approaches traditionally extrapolate from SCLC regimens. Extrapulmonary sites commonly include gastrointestinal tract locations (colon, pancreas, esophagus with universally poorly differentiated presentations, gallbladder) and genitourinary organs (cervix, ovaries, rarely endometrial, bladder). Prostate NEC typically evolves from conventional adenocarcinoma under hormonal therapy pressure.

Standard therapy has consisted of platinum-etoposide combinations using cisplatin or carboplatin, with some centers employing platinum-irinotecan based on Japanese Phase 3 trial data demonstrating comparable outcomes. This approach has remained standard care for 4 to 5 decades despite suboptimal outcomes and uncertain applicability to gastrointestinal primaries compared to lung cancers.