NMSC is the most common cancer occurring after organ transplantation, after a median time of 5–8 years, and about half of transplanted patients with a primary NMSC develop a second NMSC (2010, 2010, 2006). The burden of morbidity related to NMSC may be severe. The localization of cancer on the head and face may require complex surgical procedures, and the recurrence rate after surgery is increased in comparison to immunocompetent people (2011). Death due to metastatic dissemination of SCC is rare, as observed in our cohort (Table 4), and the impact of NMSC on overall transplant related mortality and graft survival is uncertain (2011, 2011). Incidence rates of noncutaneous cancer in the present study were comparable to those reported in other studies, ranging from 13% at 10 years to 30% after 20 years (2008, 2011, 2011). An excess risk of cancer, compared to an age- and sex-matched reference population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma, and cancer of cervix uteri and of thyroid. These cancers, with the exception of thyroid cancer, are also detected in patients with AIDS, thus supporting the role of reduced immune surveillance in pathogenesis (2011, 2011, 2007, 2009, 2009). The increased risk of thyroid cancer in transplanted patients has recently been described in a meta-analysis (2010). The number of cancers of the small intestine and of the salivary glands was limited but significantly higher than expected in an age- and sex-matched reference population. Given our inability to assess the role of enhanced clinical surveillance inherent in transplant follow-up on the detection of these rare tumors, caution should be exercised in overinterpreting the risk of these tumors in the transplant population. Further studies are needed to determine whether these tumors are actually influenced by transplant-associated therapies. No excess risk for other common epithelial cancers including breast, colon and prostate cancers as well as melanoma was observed, suggesting the heterogeneous role of immune surveillance against tumors. An excess risk for lung, bladder, stomach and pancreas cancer in kidney transplanted patients has been reported in various studies (2011, 2011), but not in the present study, possibly due to the smaller cohort of patients. Patients in the waiting list for kidney transplantation must be therefore extensively screened for cancer including salivary glands, small intestine and thyroid glands (2010, 2009, 2012, 2010). In our cohort overall mortality rates due to cancer were similar to the general population, with an excess risk only in patients at the age of 50 years or younger, in agreement with Kiberd et al. (2009). In this study patients younger than 50 years had higher cancer-related SMR, whereas those who were older and diabetic had a reduced cancer-related SMR, due to competing risk of cardiovascular mortality (2009). A possible bias is represented by the low number of patients and by the lack of information about cancer staging, but transplanted patients undergo a strict medical screening and follow-up, and cancers are usually detected at an early stage, and may have thus a better prognosis (2008, 2009). Our data confirm the severe prognosis of posttransplant lymphomas (2010). The detection of an excess mortality due to carcinoma of the native kidney in our cohort is in contrast with the reports of a favourable prognosis of this cancer in transplanted patients, if compared to nontransplanted patients (2012, 2010). The reduced number of patients in our cohort, and the different study design of the studies cited, may possibly explain these discrepancies, that need to be further investigated.
Limited data exist about the occurrence of second cancers in solid organ transplant recipients (2003, 2006). The occurrence of a second NMSC in nearly 40% of transplanted patients with a first NMSC is well established (14–16), and it has been confirmed in the present study.
The number of second noncutaneous cancers in patients with a first noncutaneous cancer is small, but higher than expected in the whole cohort of transplanted patients, and this is a main novelty of our study. Due to the limited number of second noncutaneous cancers, we could not determine which type of noncutaneous cancer could predict the risk of a second cancer and possible risk factors. Our findings are in agreement with the review by Ng et al (2010, 2008) and with the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (USA), reporting a second cancer in about 8% of cancer patients (irrespective of the type of the first cancer) and an observed/expected ratio of at least 1.27, for patients diagnosed of cancer at the age of 50–60, that is the median age at the diagnosis of our cohort (2006). Our study failed to demonstrate an excess risk of second noncutaneous cancers in patients with a previous NMSC. This is possibly due differences in the biology and immunology of NMSC and noncutaneous cancers and to the small size of our cohort. Our study reports an increased risk of primary and second cancers in renal transplant recipients when compared to nonimmunosuppressed patients. The type of the second cancer is determined by the type of the primary, with patients with primary NMSC being at risk of subsequent NMSC, and patients with noncutaneous cancers being at risk of noncutaneous cancers, emphasizing again the role of factors specific to each cancer type. Interestingly enough, cancer mortality seems not to be increased, if compared to the reference population. Further studies on larger cohorts should better investigate the phenomenon of second neoplasms, therapeutic strategies, and modulation of immunosuppressive therapy.