Sarcoma arising in Paget's disease of bone: declining incidence and increasing age at presentation

Paget's disease is presenting at older ages, with a trend to monostotic disease, associated with lower serum total alkaline phosphatase (serum total ALP) levels. Sarcomatous transformation is a rare complication, which only half a century ago had a median age of presentation of less than 60 years. We have investigated whether sarcomatous change exhibits increasing age at presentation, whether the trend to monostotic Paget's disease exists, whether male predominance in sarcoma still continues and explored factors that might affect survival.

Notes of all patients from the Royal Orthopaedic Hospital, Birmingham primary malignant bone tumour registry were reviewed and all cases of Pagetic sarcoma since 1975 extracted. In addition to basic demographic data, mode of presentation, skeletal involvement by Paget's disease, history of treatment, presence of pulmonary metastases, serum total ALP levels and survival were obtained.

Unequivocal Pagetic sarcoma was identified in 32 patients (23 M, 9 F). Age at presentation was 73.8 years with no sex difference and with known pre-existing Paget's disease in 42%. Only 15% had received any specific Paget's disease treatment. Serum total ALP was not invariably markedly elevated (compared with non-sarcomatous disease) and was related to the number of skeletal sites, but not to the sarcoma histological subtype. Paget's disease was monostotic in 46%. Pagetic sarcoma fell from 23% to 8% of primary bone sarcoma referrals in patients aged over 50 years between the decades 1986-1995 and 1996-2005. Median survival remained poor at 0.66 years. Survival of greater than 2 years occurred in 4 patients, one of whom with a low grade Pagetic sarcoma being alive at 12 years follow up.

The proportion of Paget's disease patients with sarcoma has fallen steadily since Paget's original report and is now about 0.3%, the decline predating availability of effective therapy. Sarcoma is not necessarily associated with very high serum total ALP. It is present amongst polyostotic cases in the expected proportion suggesting that more widespread skeletal involvement by Paget's disease is not a significant risk factor for malignant transformation. Sarcoma is presenting later concurrent with the advancing age of non-malignant disease, but male predominance continues. Pagetic sarcoma is now rare, continues to have a poor prognosis and is often the presenting feature of the disease.