The epidemiology of metastases in neuroendocrine tumors.

The epidemiology of metastases in neuroendocrine tumors (NETs) is virtually unknown. The present novel approach took use of two nationwide Swedish registers to assess the distribution of metastatic sites in comparison to adenocarcinoma. 7,334 patients with NET were identified from the Swedish Cancer Registry. Metastatic sites were identified from the National Patient and Cause of Death Registries. Sites of metastasis were investigated depending on the primary site of NET. The metastatic potential of NET was assessed. The liver was the most common site of metastasis (82% of patients with metastases), and the small intestine was the most common source of NET metastases. Of all patients with metastatic lung NETs, 66% had liver metastases, whereas the corresponding number for adenocarcinoma of lung was only 20%. The risk of metastasis was highest if the primary was in the small intestine or pancreatohepatobiliary tract, whereas it was lower with appendiceal and rectal NET. Men had more bone metastases compared to women. Patients with metastatic NET had worse prognosis if the primary site was unknown (11 months, 9% of NET patients) compared to those whose primary was known (19 months). The metastatic potential of NETs varies profoundly depending on the primary site. NETs show a clear preference to metastasize to the liver. Surveillance of liver metastases may enable earlier diagnosis and treatment. In liver metastases from NET, the small intestine should be suspected as the primary site, whereas the lung should be suspected in nervous system metastases of NET origin.

Causes of death in patients with extranodal cancer of unknown primary: searching for the primary site.

BACKGROUND: Cancer of unknown primary (CUP) is a fatal cancer, accounting for 3-5% of all diagnosed cancers. Finding the primary site is important for therapeutic choices and we believe that the organ which is designated as the cause of death may give clues about the primary site. METHODS: A total of 20,570 patients with CUP were identified from the Swedish Family-Cancer Database. Causes of death--as reported in the death certificate--were investigated, analyzing reported metastatic sites and histological subtypes separately. Survival was compared with metastatic cancer with a known primary tumor. RESULTS: An organ-specific cancer could be identified as a cause of death in approximately 60% of all CUP patients with adenocarcinoma or undifferentiated histology. In adenocarcinoma, lung cancer was the most frequent cause of death (20%), followed by pancreatic cancer (14%), and ovarian cancer (11%). Lung cancer was the most common cause of death in patients with CUP metastases diagnosed in the nervous system (69%), respiratory system (53%), and bone (47%), whereas ovarian cancer was the most common cause of death when CUP was diagnosed in the pelvis (47%) or the peritoneum (32%). In CUP diagnosed in the liver, liver and pancreatic cancers accounted for 26% and 22% of deaths, respectively. Also in squamous cell CUP, lung cancer was the most common cause of death (45%). CONCLUSIONS: According to the causes of death, the primary site appeared frequently to be either the organ where CUP metastases were diagnosed or an organ which may be traced through the known metastatic patterns of different cancer types.

Site-specific survival rates for cancer of unknown primary according to location of metastases.

Cancer of unknown primary (CUP) is diagnosed at the metastatic stage and despite extensive diagnostic work-up the primary tumor often remains unidentified. Limited population-based survival data are available for metastatic location and none are available that link the location with the cause of death, which might give clues about the tissue-of-origin. A total of 9,306 CUP patients with extranodal metastases of adenocarcinoma and undifferentiated histology were identified from the Swedish Cancer Registry. Hazard ratios (HRs), mean survival times and Kaplan-Meier survival curves were provided according to CUP location at diagnosis and cause of death. The median survival was shortest (2 months) for patients with liver and longest (5 months) for those with nervous system metastases. Lung cancer was the most common cause of death in patients with CUP metastasis in the respiratory system, nervous system, bone and skin, with a median survival of 3 months. Patients with peritoneal/retroperitoneal and pelvical metastasis died not only of ovarian cancer, with a favorable median survival of 8 months, but also of pancreatic and colorectal cancers. Patients with pancreatic, liver, biliary and colorectal cancers with liver metastasis succumbed quickly. The data show that the location of metastases predicts site-specific cancer deaths which in turn may point to the hidden primary tumor. The results should facilitate the management of CUP in proposing that the diagnostic arsenal should target the lungs when metastases are diagnosed in the respiratory or nervous system, bone or skin; ovarian tumors should be suspected after diagnosis of pelvical metastases.

Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer.

BACKGROUND: Cancer of unknown primary site (CUP) is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. METHODS: 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs) of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. RESULTS: Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66-0.72]). The exceptions were cancer of the pancreas (1.71 [1.54-1.90]), liver (1.58 [1.36-1.85]), and stomach (1.16 [1.02-1.31]). For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06-1.46]). The median survival time of CUP patients was three months. CONCLUSIONS: Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the metastatic process at the population level demonstrated large survival differences in organ defined metastases depending on the original cancer.

What do prostate cancer patients die of?

BACKGROUND: A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death. METHODS: Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death. FINDINGS: Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16-1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09-1.37), and heart failure (HR, 1.18; 95% CI, 1.11-1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14-2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55-1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84-1.96). INTERPRETATIONS: Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.

Clinical landscape of cancer metastases.

Population-based data on metastatic patterns are lacking because cancer registries seldom record metastases. This study uses a novel population-based approach to identify metastases and describes metastatic pathways from 14 common primary cancers to 12 specific metastatic sites. A total of 179 581 patients with metastatic cancer were identified from the Swedish Cancer Registry and metastatic sites were identified using the Cause of Death Register and the National Patient Register. Patterns of metastatic spread were described across age and sex. In men, colorectal cancer was the main source of lung, peritoneal, and liver metastases. Lung cancer was the main origin of pleural and nervous system metastases. Prostate cancer dominated bone metastases but had minor contribution to other metastatic sites. Among women, breast cancer was the dominant origin of most metastatic sites, with the exception of peritoneum which was ruled by metastases from the ovary. As other exceptions, for nervous system metastases, lung cancer was the origin of metastases somewhat more frequently than breast cancer and for liver metastases, colorectal cancer was the main origin instead of breast cancer. The present achievement was to implement the first nationwide description of clinical landscape of cancer metastases, with an aim to serve as a reliable source for clinicians and researchers.

Patterns of metastasis in colon and rectal cancer.

Investigating epidemiology of metastatic colon and rectal cancer is challenging, because cancer registries seldom record metastatic sites. We used a population based approach to assess metastatic spread in colon and rectal cancers. 49,096 patients with colorectal cancer were identified from the nationwide Swedish Cancer Registry. Metastatic sites were identified from the National Patient Register and Cause of Death Register. Rectal cancer more frequently metastasized into thoracic organs (OR = 2.4) and the nervous system (1.5) and less frequently within the peritoneum (0.3). Mucinous and signet ring adenocarcinomas more frequently metastasized within the peritoneum compared with generic adenocarcinoma (3.8 [colon]/3.2 [rectum]), and less frequently into the liver (0.5/0.6). Lung metastases occurred frequently together with nervous system metastases, whereas peritoneal metastases were often listed with ovarian and pleural metastases. Thoracic metastases are almost as common as liver metastases in rectal cancer patients with a low stage at diagnosis. In colorectal cancer patients with solitary metastases the survival differed between 5 and 19 months depending on T or N stage. Metastatic patterns differ notably between colon and rectal cancers. This knowledge should help clinicians to identify patients in need for extra surveillance and gives insight to further studies on the mechanisms of metastasis.

Metastatic spread in patients with gastric cancer.

BACKGROUND: The epidemiology of metastatic gastric cancer is unexplored because cancer registries seldom cover metastatic involvement apart from "present or not". We used a novel approach by utilizing Swedish registers to assess metastatic spread in gastric cancer. To our knowledge, this is the first nationwide description of metastases in gastric cancer. RESULTS: The most common sites of metastasis were liver (in 48% of metastatic cancer patients), peritoneum (32%), lung (15%), and bone (12%). Metastases to the lung, nervous system, and bone were more frequent in cardia cancer and men, whereas non-cardia cancer more frequently metastasized within the peritoneum. Signet ring adenocarcinomas more frequently metastasized within the peritoneum, bone and ovaries, and less frequently to the lungs and liver compared with generic adenocarcinoma. The liver and the peritoneum were commonly single metastases while lung metastases occurred frequently together with liver metastases. The median survival in metastatic gastric cancer was 3 months, worst among those with bone and liver metastases (2 months). METHODS: A total of 7,559 patients with gastric cancer were identified. Metastatic patterns and survival depending on sex, age, stage, anatomical location (cardia and non-cardia), and histological type were assessed. CONCLUSIONS: The patterns of metastasis differ notably depending on histological type. Cardia cancer exhibits a completely different metastatic behavior than non-cardia cancer. Awareness of the differing patterns may guide in tailored diagnosis of metastases. Survivors from cardia cancer would benefit from increased surveillance of extraperitoneal metastases. Bone metastases should be considered in patients with signet ring adenocarcinoma if symptoms emerge.