Importance of long-term surveillance after curative esophagectomy for esophageal squamous cell carcinoma

Summary Background The long-term outcomes after esophagectomy for esophageal cancer remain uncertain and the optimal surveillance strategy after curative surgery remains controversial. Methods In this study, the clinicopathological characteristics of patients who underwent curative thoracic esophagectomy between 1991 and 2015 at Toranomon Hospital were retrospectively analyzed and reviewed until December 2020. We evaluated the accumulated data regarding the pattern and rates of recurrence and second malignancy. Results A total of 1054 patients were eligible for inclusion in the study. Of these, 97% were followed up for 5 years, and the outcomes after 25 years could be determined in 65.5%. Recurrence was diagnosed in 318 patients (30.2%), and the most common pattern was lymph node metastasis (n = 168, 52.8%). Recurrence was diagnosed within 1 year in 174 patients (54.7%) and within 3 years in 289 (90.9%). Second malignancy possibly occurred through the entire study period after esophagectomy even in early-stage cancer, keeping 2%–5% of the incidental risk. There was no significant difference in the prognosis between 3-year survivors with and without a second malignancy. Conclusions Most recurrences after resection of esophageal cancer occurred within 3 years regardless of disease stage. However, these patients have an ongoing risk of developing a second malignancy after esophagectomy. Further consideration is required regarding the efficacy of long-term surveillance.

A Multicenter Epidemiological Study on Second Malignancy in Non-Syndromic Pheochromocytoma/Paraganglioma Patients in Italy

No studies have carried out an extensive analysis of the possible association between non-syndromic pheochromocytomas and paragangliomas (PPGLs) and other malignancies. To assess the risk of additional malignancy in PPGL, we retrospectively evaluated 741 patients with PPGLs followed-up in twelve referral centers in Italy. Incidence of second malignant tumors was compared between this cohort and Italian patients with two subsequent malignancies. Among our patients, 95 (12.8%) developed a second malignant tumor, which were mainly prostate, colorectal and lung/bronchial cancers in males, breast cancer, differentiated thyroid cancer and melanoma in females. The standardized incidence ratio was 9.59 (95% CI 5.46–15.71) in males and 13.21 (95% CI 7.52–21.63) in females. At multivariable analysis, the risk of developing a second malignant tumor increased with age at diagnosis (HR 2.50, 95% CI 1.15–5.44, p = 0.021 for 50–59 vs. <50-year category; HR 3.46, 95% CI 1.67–7.15, p < 0.001 for >60- vs. <50-year). In patients with available genetic evaluation, a positive genetic test was inversely associated with the risk of developing a second tumor (HR 0.25, 95% CI 0.10–0.63, p = 0.003). In conclusion, PPGLs patients have higher incidence of additional malignant tumors compared to the general population who had a first malignancy, which could have an impact on the surveillance strategy.

Increased risk of breast cancer-specific mortality among cancer survivors who developed breast cancer as a second malignancy

Background Cancer survivors who develop breast cancer as a second malignancy (BCa-2) are common. Yet, little is known about the prognosis of BCa-2 compared to first primary breast cancer (BCa-1). Methods Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 883,881 patients with BCa-1 and 36,313 patients with BCa-2 during 1990–2015. Compared with patients with BCa-1, we calculated hazard ratios (HRs) of breast cancer-specific mortality among patients with BCa-2, using multivariable Cox regression. Results During the follow-up (median 5.5 years), 114,964 and 3829 breast cancer-specific deaths were identified among BCa-1 and BCa-2 patients, respectively. Patients with BCa-2 had more favorable tumor characteristics and received less intensive treatment e.g., surgery and chemo−/radio-therapy, compared to patients with BCa-1. When adjusting for demographic factors, patients with BCa-2 were at similar risk of breast cancer-specific mortality (HR 1.00, 95% CI 0.97–1.03) compared to patients with BCa-1. However, when additionally controlling for tumor characteristics and treatment modes, BCa-2 patients were at an increased risk of breast cancer-specific mortality (HR 1.11, 95% CI 1.08–1.15). The risk elevation was particularly greater when the first malignancy was lung, bladder, ovarian or blood malignancy (HRs 1.16–1.85), or when the first malignancy was treated with chemotherapy and radiotherapy (HR 1.44, 95% CI 1.28–1.63). Conclusions Overall, patients with BCa-2 have worse breast cancer-specific survival, compared with their BCa-1 counterparts, although the risk elevation is mild. High-risk subgroups based on first malignancy’s characteristics may be considered for active clinical management.