While splenectomy combined with adjuvant chemotherapy remains the standard of care for hemangiosarcoma, survival times are notoriously short, particularly for dogs with stage III disease, where median survival times often range from just 68 to 136 days.
For decades, the prognostic conversation has been dominated by the three-tiered WHO staging system. While tumors confined to the spleen (Stage I) carry a more favorable prognosis and distant metastasis (Stage III) has historically portended poor outcomes, a recent multi-institutional retrospective study suggests the anatomic location of metastatic disease may be as prognostically relevant as its presence.
The study reviewed medical records from 2014 to 2024 across three institutions, including dogs that underwent splenectomy with histologically confirmed splenic HSA. In line with previous reports, metastases had already occurred in approximately 42% of cases at diagnosis. However, with 48% of patients staged only with thoracic radiographs and abdominal ultrasound, metastases in sites like muscle were likely underdiagnosed, suggesting the true incidence may be higher. Advanced imaging such as total-body contrast-enhanced CT may offer more accurate staging and prognostic clarity.
Confirming its role as a primary filter of portal and systemic circulation, the liver was the most common site of metastasis and the most frequently identified site at death, with hemoperitoneum being the ultimate cause of death for most patients. Other documented sites included the lungs, mesentery, omentum, and muscle.
The study’s most compelling finding emerged when they correlated metastatic site with survival. On univariate analysis, hepatic metastasis was a clear negative prognostic indicator, significantly impacting time to survival. This is clinically intuitive; bleeding from often-cavitated, multifocal liver lesions is catastrophic and difficult to manage surgically or durably with chemotherapy.
However, the story differed for metastases elsewhere. Dogs with muscle metastases did not have worse outcomes than those without. The authors propose the muscular microenvironment may be hostile to tumor growth and, more importantly, to life-threatening hemorrhage. Unlike the highly vascular liver, bleeding into a muscle compartment is less likely to cause acute, fatal decompensation.
Similarly, while not reaching statistical significance, dogs with pulmonary metastases trended toward longer survival than those with liver involvement. This aligns with observations that pulmonary metastases are often smaller, non-cavitated, and less prone to spontaneous hemorrhage at diagnosis. They may also be more responsive to systemic therapy than bulky, cavitated visceral lesions.
These findings suggest a paradigm shift: a dog with a solitary, small pulmonary nodule (Stage III) may have a fundamentally different biological trajectory than one with multiple cavitated liver masses (also Stage III). The current staging system, while valuable, may lump together patients with distinct disease behaviors.
The study reinforces that dogs undergoing splenectomy followed by adjuvant chemotherapy lived longer than those treated with surgery alone. However, the type of chemotherapy used added another layer of nuance.
For the overall population, the specific protocol, whether maximum-tolerated dose anthracycline-based or metronomic chemotherapy, did not significantly impact overall median survival time. This echoes previous research suggesting any adjuvant chemotherapy is better than none.
But in stage III disease, a different picture emerged. In patients with advanced disease, AC-based chemotherapy resulted in a survival advantage over MC protocols. This suggests dose-intensive chemotherapy may be necessary for macroscopic disease, whereas metronomic scheduling might be better suited for the adjuvant, microscopic setting. While selection bias is possible, the finding warrants consideration when discussing options with owners of stage III patients.
The authors suggest that different behaviors of metastatic lesions may reflect different underlying tumor biologies, a concept already observed in canine osteosarcoma. This aligns with emerging research into the genetic landscape of hemangiosarcoma, where germline variants have been linked to survival.
For now, this study provides veterinarians with a more sophisticated tool for navigating difficult client conversations. By moving beyond the broad strokes of the stage III label, they can offer more accurate, individualized prognoses and have more meaningful discussions about treatment goals—whether pursuing dose-intense chemotherapy for a patient with a single lung lesion or focusing on quality of life for a patient with diffuse liver involvement.
