**2.1. Epidemiology and risk factors**

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. In almost all populations, males have higher liver cancer rates than females, with male/female ratios usually averaging between 2:1 and 4:1 [1, 2].

HCC global distribution varies by region, incidence rate, sex, and also, by etiology. Normally, HCC incidence in female peaks 5 years later than males. Age-specific onset patterns are likely related to differences in the dominant hepatitis virus in population, age at viral infection, and the existence of other risk factors. As for average age at infection, normally, HCV carriers became infected in adulthood, while HBV carriers tend to become infected in childhood [2].

Recently, a significant increase in HCC incidence in hepatitis-free patients was noted; this index had a boost and went from 22% in 2000–2004 to 31% in 2010–2014 (database ITALICA) [5]. Among nonvirus-related hepatopathy, incidence of HCC in Alcoholic fatty liver disease patients (AFLD-patients) remains stable (17 vs. 19%), while a significant incidence increase was seen in Non Alcoholic fatty liver disease Patients (NAFLD-Patients) or in patients suffering from cryptogenic cirrhosis (0.5 vs. 9%) [5].

Often NAFLD-patients are demanding to treat; patients in this group have commonly several comorbidities such as metabolic syndrome; therefore, they need a more accurate and multidimensional clinical evaluation in order to choose the best treatment and achieve the best outcome from their condition.

HCV interferon-mediated clearance, associated with mild to severe fibrosis reduces hepatopathy progression and cirrhosis incidence, thus HCC's incidence reduction in SVR patients is expectable.

HCC hazard in HBV replication-controlled infection is reduced but not abolished, although effective antiviral therapy reduces HCC incidence in HBV- or HCV-positive patients [6].

Sudden HCC recurrence was reported by several papers after Direct Acting Antiretrovirals (DAA) mediated HCV clearance [7]. Other papers have found similar incidence of HCC after DAA-mediated HCV clearance when compared to IFN-mediated SVR but considering an overall 24-month follow-up [7]. HCC incidence after HCV clearance is still not sufficiently evaluated.

#### **2.2. Elderly management and evaluation**

More than two-third of patients newly diagnosed with HCC are aged >65 years [8], and this number is expected to increase as the world population ages. Furthermore, there is heterogeneity in the aging process, which further contributes to the complexity of treatment decisions. These factors contribute to age-related variations in treatment patterns and outcomes, potentially resulting in increased likelihood of under- or overtreatment, which can influence both risk of treatment toxicity and survival [9].

Geriatric patients may be extremely complex to treat due to comorbidities that may affect them. Therefore, a clinical evaluation is fundamental to assess the best treatment for each patient.

clear evidence that GA items independently predict OS in a variety of oncology diseases and treatment settings. Poorer OS in older patients with cancer and deficits identified in geriatric domains might potentially be explained by several factors (e.g., increased risk of death resulting from causes other than cancer, increased death resulting from cancer because of less

HCC in Elderly Patients. Curative Intraoperative Strategies and Management in Recurrences

http://dx.doi.org/10.5772/intechopen.79748

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Patients with risk factors, in particular if older in age, must be lifelong under clinical surveillance for HCC onset. Principal conditions that require normally a twice per year follow-up are advanced cirrhosis, active HCV infection or cleared HCV infection, and HBV-controlled infection. Surveillance is made by liver-US and serum α-fetoprotein assessment. Oncologicalmarker-only surveillance is not recommendable and since cirrhotic parenchyma is on average poorly explorable, imaging shall be performed by a hepatobiliary dedicated team. Suspect nodules shall be further investigated by CT scan or hepatospecific MRI, which allows to make in the same session either a noninvasive diagnosis or staging when nodule is >10 mm in diameter [11]. Noninvasive diagnosis is cost-effective and a big advantage especially for elderly in

Patients older in age are the cohort that receives the highest benefit in early cancer detection since lower stage HCCs are associated with less invasive interventions, faster recovery, lower

Therefore, geriatric patients shall be educated to strictly comply to follow-up timing and to

HCC shall never be considered as a single-cell malignancy: it is a whole organ malignancy; cell transformation is due to liver damage from hepatotropic viruses, toxins, and metabolic syndrome [2, 4]. Even a radical liver resection that cures the single malignancy does not exclude the onset of further lesions and rarely metastases after radical resection is possible [12].

The aim of HCC treatment is to freeze the disease into a chronic stage and to treat lesions as they show. There are several possible treatments that allow in some cases extremely long

Management of HCC patients can be extremely complex, so only dedicated multidisciplinary

Hepatic resection is the gold standard in noncirrhotic liver. In western countries, HCC inci-

Patients with these pathologic conditions can develop HCC in the absence of cirrhosis or severe fibrosis [14], although hepatic parenchyma shall not be considered healthy since steatosis is determinable in 50% of patients and steatohepatitis (NASH) in 25% [15, 16]. A

teams shall treat these patients who are regularly discussed into liver units [4].

dence is raising, mostly due to NAFLD and metabolic syndrome [13].

change their lifestyle in order to ameliorate liver function and reduce liver damage.

aggressive treatment, or death resulting from complications of cancer treatment) [9].

poor performance status.

mortality rate, and better QoL [4].

survival, even in metastatic patients [12].

**3. Surgical therapy**

**3.1. Hepatic resection**

Aspects that must be considered comprehend not only biological age, HCC stage, and liver status, but also general patient conditions, performance status, and, in particular, individual and familial psychological frame, will to fight against the disease, and treatment tolerability. All these parameters are included into the concept of physiological age which goes far beyond chronological age and considers many crucial aspects of aging which is an extremely individual process.

Since chronologic age alone is a poor descriptor of heterogeneity in the aging process, a systematic and evidence-based way to assess physiological age is needed to guide treatment decisions.

Comprehensive geriatric assessment (CGA) is defined as a multidimensional, interdisciplinary diagnostic process focusing on determining an older person's medical, psychosocial, and functional capabilities to develop a coordinated and integrated plan for treatment and longterm follow-up [10] (**Table 1**).

Important reasons to perform GA in older patients with cancer are detection of unidentified problems and risks for which targeted interventions can be applied and prediction of adverse outcomes (e.g., toxicity, other relevant items such as functional or cognitive decline, postoperative complications); and better estimation of residual life expectancy and lethality of the malignancy in the context of competing comorbidities and general health problems. There is


**Table 1.** Considered parameters in Comprehensive geriatric Assessment.

clear evidence that GA items independently predict OS in a variety of oncology diseases and treatment settings. Poorer OS in older patients with cancer and deficits identified in geriatric domains might potentially be explained by several factors (e.g., increased risk of death resulting from causes other than cancer, increased death resulting from cancer because of less aggressive treatment, or death resulting from complications of cancer treatment) [9].

Patients with risk factors, in particular if older in age, must be lifelong under clinical surveillance for HCC onset. Principal conditions that require normally a twice per year follow-up are advanced cirrhosis, active HCV infection or cleared HCV infection, and HBV-controlled infection. Surveillance is made by liver-US and serum α-fetoprotein assessment. Oncologicalmarker-only surveillance is not recommendable and since cirrhotic parenchyma is on average poorly explorable, imaging shall be performed by a hepatobiliary dedicated team. Suspect nodules shall be further investigated by CT scan or hepatospecific MRI, which allows to make in the same session either a noninvasive diagnosis or staging when nodule is >10 mm in diameter [11]. Noninvasive diagnosis is cost-effective and a big advantage especially for elderly in poor performance status.

Patients older in age are the cohort that receives the highest benefit in early cancer detection since lower stage HCCs are associated with less invasive interventions, faster recovery, lower mortality rate, and better QoL [4].

Therefore, geriatric patients shall be educated to strictly comply to follow-up timing and to change their lifestyle in order to ameliorate liver function and reduce liver damage.

HCC shall never be considered as a single-cell malignancy: it is a whole organ malignancy; cell transformation is due to liver damage from hepatotropic viruses, toxins, and metabolic syndrome [2, 4]. Even a radical liver resection that cures the single malignancy does not exclude the onset of further lesions and rarely metastases after radical resection is possible [12].

The aim of HCC treatment is to freeze the disease into a chronic stage and to treat lesions as they show. There are several possible treatments that allow in some cases extremely long survival, even in metastatic patients [12].

Management of HCC patients can be extremely complex, so only dedicated multidisciplinary teams shall treat these patients who are regularly discussed into liver units [4].
