Case Report of Synchronous Prostate, Hepatocellular, and Rectal Carcinomas and Review of the Literature

Synchronous occurrence of three histopathologically distinct malignant tumors is a rare event, and there are no definitive guidelines about the optimal treatment of these patients. We report a case of synchronous prostate, hepatocellular, and rectal carcinomas and discuss our therapeutic strategy that resulted in excellent clinical results.


Introduction
Synchronous malignancies are defined as tumors diagnosed within two to six months of the initial diagnosis of a primary tumor and occur in 0,002% to 1,96% of cancer patients [1,2]. This frequency is increasing despite a general decline in cancer deaths since 1991 because of the increased lifespan of the general population secondary to proper screening, earlier diagnosis, improvements in treatment, and surveillance of patients [3]. Management of synchronous cancers is challenging [4]. We present a patient with synchronous liver, colorectal, and prostate cancers treated by a multidisciplinary approach with an excellent clinical outcome.

Case Presentation
A 67-year-old man presented with a history of change of bowel habits, blood in stool, and weight loss. His past medical history included only tobacco and alcohol use. According to his family history, two of his first-degree relatives had developed colonic cancer. A colonoscopy revealed the presence of a 4 cm mass approximately 10 cm from the anal verge and was confirmed to be a well-differentiated colon adenocarcinoma at a biopsy. Laboratory tests showed elevated serum carcinoembryonic antigen (CEA) (8,07 ng/ml), elevated serum prostate-specific antigen (PSA) (17,87 ng/ml), and elevated α-FP (17,9 ng/ml). The patient was seronegative for HBsAg and anti-HCV (IgM and IgG). His liver function tests were within normal limits. The abdominal MRI showed the presence of an 11 × 10, 5 × 10, 5 cm mass in the right hepatic lobe, with radiologic features consistent with a primary liver lesion (Figures 1 and 2). The CTguided liver biopsy revealed a well-differentiated hepatocellular carcinoma. Additionally, because of the elevated PSA values, a prostate biopsy was performed. Seven core biopsies were taken from the left prostatic lobe and eight from the right lobe, and all of them were positive for prostatic adenocarcinoma (Gleason score 3 + 4 = 7/10).
Given the patient's good performance status, surgical resection for the hepatocellular carcinoma was considered. However, because of the small liver remnant, it was decided to first perform transarterial chemoembolization, to partially control the hepatocellular carcinoma ( Figure 3). Two weeks later, the rectal carcinoma was treated by low anterior resection ( Figure 4). After six weeks, right portal vein embolization was performed to allow for hypertrophy of the liver remnant ( Figure 5). Finally, one month later, the hepatocellular carcinoma was treated by right hepatectomy (Figures 4 and 6). Active surveillance was adopted for the prostate cancer.
Histopathological evaluation of the rectal specimen showed a moderately differentiated adenocarcinoma Stage IIA (T3N0M0) and a well-differentiated hepatocellular adenocarcinoma Stage IIIA (T3N0M0). Recovery was uneventful, and the patient remained disease-free up until the 2-year follow-up when he died of acute myocardial infarction.

Discussion
According to the Surveillance Epidemiology and End Results (SEER) project and the International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC), synchronous multiple primaries are defined   2 Case Reports in Surgery as two or more independent primaries diagnosed within two to six months of the initial diagnosis [4,5]. Factors associated with increased risk of developing multiple primary malignancies include environmental exposures, genetic factors (family cancer syndromes and other genetic susceptibility factors), lifestyle (tobacco and alcohol consumption), immunodeficiency syndromes (either acquired or inherited), and carcinogenic effects of cancer treatment [6].

Case Reports in Surgery
Male genital cancers and urinary tract cancers are the most widespread combination of synchronous multiple malignancies, followed by colorectal and noncolorectal digestive tract cancers [2]. Specifically, a synchronous occurrence of rectal and prostate cancers has been described approximately in 0,1%-30,5% of cancer patients [7,8]. In HCC patients, prostate and rectal tumors coexist in 0,05% and 0,4% of cases, respectively [9,10]. Triple synchronous primary tumors involving hepatocellular, rectum, and prostate cancers are a rare occurrence with few cases reported in the English literature (Table 1).
During pretreatment work-up of cancer patients, the diagnosis of a second mass raises the possibility either of metastasis or of a synchronous primary malignant tumor. When multiple tumors are pathologically confirmed, the therapeutic approach is decided after staging each tumor independently. Moreover, the patient's age, life expectancy, and comorbidities as well as the tumor's biological behavior should be considered. Treatment options include curative surgical resection of each tumor, when possible in a single setting, radiation, or chemoradiation [26][27][28]. As there exist no systematic and authoritative treatment guidelines for the treatment of synchronous primary malignancies, the aim is to cover all primaries without negatively affecting the overall patient's outcome.
Especially for triple synchronous carcinomas, treatment strategies remain poorly defined. Several studies have failed to show a significant impact of a second extra hepatic malignancy on the survival of patients with HCC, suggesting that aggressive treatment of HCC by curative resection is an inde-pendent prognostic factor associated with a good outcome [29,30]. In the present case, we prioritized the cure of the hepatocellular carcinoma independently of two other malignancies. However, the successful implementation of hepatectomy represented a therapeutic challenge due to the large size of the tumor and the small functional liver remnant. We opted for sequential TACE and PVE of the hepatocellular carcinoma as this strategy is associated with longer recurrence-free survival [31,32]. TACE allowed for local control of the hepatocellular carcinoma during which the rectal carcinoma was resected, and PVE was performed allowing eventual radical HCC excision. Taking into account the presence of two other synchronous malignancies and patient's preferences, active therapy of prostate cancer was withheld, and active surveillance was adopted. Recent guidelines for the follow-up of HCC after liver resection recommend dynamic CT/MRI studies every 3 months during the first year and every 6 months thereafter [33]. Follow-up recommendations for rectal carcinoma include rectosigmoidoscopy and CEA testing every 6 months for 5 years and abdominal and chest CT scan annually for 3 years [34]. Our patient kept the above-mentioned follow-up protocol for six months and opted for a simple clinical follow-up for two years, during which he remained in an excellent clinical condition.

Conclusion
Our case highlights the value of targeted curative therapy of synchronous malignancies in a framework of a patient- Figure 6: (a) CT scan before TACE and PVE. (b) One month after PVE and three months after TACE, anticipated hypertrophy of LLL is observed. On CT scan, one month (c) and three months (d) after liver resection, there is no evidence of HCC recurrence. Significant hypertrophy of the liver remnant is noted. 5 Case Reports in Surgery centered multidisciplinary approach. We achieved an excellent result with curative therapy of two of the three synchronous lesions and opted for conservative management of the prostate cancer.