Rectal neuroendocrine tumors: Current advances in management, treatment, and surveillance

Table 1 Current evidence about available prognostic factors for either metastatic spread or tumor progression/recurrence in rectal neuroendocrine neoplasms

Prognostic factor	Cut-off	Risk of metastases	Evidence
Tumor size	15 mm	14%	Retrospective large study[27]
Grading	G2	50%	Retrospective study[30]
	G3	33%	Retrospective study[30]
Lymph node status	N2 (≥ 5 positive lymph nodes)	Not quantified	Retrospective study[35]
Depth of invasion	Invasion of the muscolaris propria	Not quantified	Retrospective study[37]

Table 2 Systemic therapies for advanced disease

Pharmacological class	Therapeutic agent	Superiority vs placebo	Main ongoing clinical trials
Somatostatin analogs	Octreotide (30 mg/4 wk i.m.)	Yes[70]	NCT04129255
	Lanreotide (120 mg/4 wk s.c.)	Yes[69]	NCT03289741 (octreotide vs lanreotide)
Cytokines	Interferon-α (3 MIU/three times a week s.c.)	Yes[72]	NCT02838342 (association with cyclophosfamide)
Targeted agents	Everolimus (10 mg/d p.o.)	Yes[73]	NCT02248012 (association with temozolomide)
	Sunitinib (50 mg/d p.o.)	Yes[74]1	NCT00056693NCT02315625
	Cabozantinib (40-60 mg/d p.o.)	NA	NCT05048901
	Sorafenib (800 mg/d p.o.)	NA	NCT00605566, NCT00131911
Radioligand therapy	177Lu-DOTATATE (Lutathera)	Yes[76]	NCT02743741, NCT03972488 (combination with LAR)
Chemotherapy	Cisplatin/carboplatin ± etoposide/irinotecan	Yes[79]	NCT03963193 (etoposide + cisplatin vs irinotecan + cisplatin)
	Streptozocin ± 5-FU ± doxorubicin	Yes[80]	NCT00602082
	5-FU ± dacarbazine ± epirubicin	Yes [81]	NA

¹Only for p-NENs.

LAR: Long-acting release octreotide; NA: Not available; 5-FU: 5-fluorouracil.