Portal vein involvement is considered one of the most fearful complications of 
hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is 
associated with aggressive tumor biology (high grade), high tumor burden (number 
and size of lesions), high levels of serum markers (AFP), poor liver function 
(deranged LFT), and poor performance status of patients. The Barcelona Clinic 
Liver Cancer staging system places HCC patients with PVTT in advanced stage 
(BCLC Stage-C). This group contains a fairly heterogeneous patient population, 
previously considered candidates for palliative systemic therapy with sorafenib. 
However, this provided modest overall survival (OS) benefit. The results of a 
recent Phase III (IMbrave150) trial favor the combination of atezolizumab and 
bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. 
While only lenvatinib proved to be non-inferior against sorafenib in a phase III 
(REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and 
cabozantinib (CELESTIAL) have been approved second-line therapy in phase III 
clinical trials. Recently, the data on the prospect of other modalities in the 
management of HCC with PVTT is mounting with favorable results. Targeting 
multiple pathways in the HCC cascade using a combination of drugs and other 
modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and 
loco-regional control. The quest for the ideal combination therapy and the 
sequence set is still widely unanswered and prospective trials are lacking. With 
the armament of available therapeutic options and the advances and refinements 
in the delivery system, down-staging patients to make them eligible for curative 
resection has been reported. In a rapidly evolving treatment landscape, 
performing surgery when appropriate, in the form of LR and even LT to achieve 
cure does not seem farfetched. Likewise, adjuvant therapy and prompt management 
of the recurrences holds the key to prolong OS and DFS. This review discusses 
the management options of HCC patients with PVTT.