What is osteosarcoma?
Osteosarcoma is the most common primary bone tumour of dogs. It more typically affects the large to giant breeds of dogs. An increased risk of disease has been identified in rottweilers (5x) and greyhounds (10x), and a possible genetic basis for disease present in rottweilers and Scottish deerhounds.The median age of onset is 7 years, with a slight male bias to tumour development.
Osteosarcoma may occur anywhere in the skeleton. However, more than 75% of tumours develop in the appendicular skeleton, with the forelimbs affected twice as commonly as the hind limbs. The proximal humerus and distal radius are the two most common locations for tumour development. In the hind limb, tumours may occur at the distal femur, or the proximal and distal tibia.
How can I tell if my pet has osteosarcoma?
Appendicular osteosarcoma usually presents as a lameness, often of acute onset. A mild, recent trauma may sometimes be described, but this is often an incidental event and not contributory to the development of the tumour. Swelling and focal pain is sometimes evident at the local site. Pathological fractures may occur due to the weakness of the affected bone. For this reason, careful appraisal of radiographs should be made when a fracture has occurred with comparatively minor trauma.
A high index of suspicion for osteosarcoma is based on presentation of an acutely lame, middle-aged to older, giant breed dog, with pain or swelling localisable to common predilection sites for tumour development. Confirming the diagnosis, and planning appropriate therapy, will require a diagnostic investigation which may include imaging, blood tests or biopsies. The extent of this investigation is often dependent on individual factors, and the nature of any treatment plan.
How is osteosarcoma diagnosed?
The radiographic appearance of osteosarcoma is often distinctive. Possible differentials include osteomyelitis (especially fungal), other primary bone tumour, or metastatic bone disease (especially mammary, myeloma, prostatic, or thymic tumours). However, fungal osteomyelitis is rare/unrecorded in the UK.
Radiographs of the chest are essential to detect occult metastasis, the presence of which has a direct bearing on immediate prognosis. Only about 10% of cases will have detectable metastasis at the time of diagnosis, but it is generally considered that most, if not all, cases will have microscopic disease at the time of diagnosis. The reason for this discrepancy is that a lung nodule must be 6-8mm in diameter to be detected radiographically – at this size it is calculated to contain close to a billion tumour cells. A CT lung scan will improve the sensitivity of detection of pulmonary metastasis. The use of nuclear scintigraphy has also been reported to detect distant skeletal metastasis. This modality is mainly employed to improve the accuracy of clinical staging prior to embarking on expensive treatments such as limb sparing procedures. Nuclear scintigraphy is very sensitive for detection of areas of increased bone activity but is not specific to tumour.
Bone biopsy is a quick, and relatively simple technique that can be used to provide a definitive diagnosis of underlying pathology. Because the radiographic appearance of bone cancer is usually quite dramatic, biopsy is not always required to proceed with a treatment plan, but it may be performed when the radiographic findings are equivocal, or treatment decisions may be affected by the precise diagnosis of the lesion. The biopsy should be performed without compromising future treatment options.
The levels of serum alkaline phosphatase (AlkP) activity in the blood of dogs with osteosarcoma is known to have some prognostic significance. Dogs with normal pre-treatment total AlkP and bone-associated AlkP activities survived significantly longer than dogs with increased pre-treatment activities (P = .001 and .003, respectively). Median survival times for dogs with normal or increased total AlkP activities before treatment were 12.5 and 5.5 months, respectively; and median survival times for dogs with normal or increased bone-associated AlkP activities before treatment were 16.6 and 9.5 months, respectively.
How is osteosarcoma treated?
It can be useful to divide the management options for osteosarcoma into those that focus on management of the pain in the limb, and those that focus on trying to reduce the progression of secondary disease and extending life. Treatment of the ‘limb’ is directed at relief of pain, and provision of mobility. Treatment of the ‘life’ is directed at control of metastatic disease, and maximising the remission period. In very broad terms, the following prognosis can be given:
Will my dog require amputation?
Although amputation is the more common treatment offered, for some dogs this option is not tenable. This may be because of pre-existing orthopaedic or neurological disease in other limbs, or in very large or heavy dogs. In these instances, limb sparing, or radiotherapy may be an option. These options, however, are not appropriate for all cases and careful counselling and case selection is important.
Amputation of the affected limb is usually well tolerated in the majority of cases. Even large and giant breed dogs can function well after limb amputation. Careful case selection is important, and a thorough orthopaedic/neurological examination should be performed to detect potential problems in the remaining limbs. Hind-limb amputees tend to have better long term function that forequarter patients, due to the greater biomechanical and load bearing function of the forelimb. A large survey of owners following amputation revealed excellent client satisfaction with the procedure. Those clients who were initially anxious were pleased with their pet’s quality of life.
Palliative radiation of primary osteosarcoma can provide local pain control, whilst preserving limb function. Radiation therapy should only be considered when amputation or limb sparing are not acceptable options for treatment. Catastrophic pathologic fracture of the limb during or after treatment is a significant risk with this technique. Furthermore, while most dogs will experience some reduction in lameness, few become fully sound and some show no improvement.
Limb sparing involves the removal of the neoplastic bone, and replacement with either a cortical allograft – a similar sized and shaped bone harvested from a cadaver, or a metallic prosthetic implant. A number of Veterinary Oncology centres around the world have developed impressive experience with limb sparing techniques. Although limb sparing of the proximal humerus, tibia and distal femur have been described, it is generally considered that tumours of the distal radius are most amenable to limb salvage techniques, with the potential for excellent clinical function.
Limb sparing is a complicated procedure and requires specialised training and experience to perform. A multi-modality approach to treatment, including pre-operative radiation or chemotherapy to reduce tumour bulk, plus the need for ongoing post-operative treatment tends to confine this procedure to large institutions. It also requires maintenance of a bone bank to ensure a suitably sized allograft will be available for all cases. Possible post-operative complications may affect up to 50% of candidates, and include osteomyelitis, graft failure, local tumour recurrence. The procedure is expensive, and significant post-operative complications can add substantially to the final bill.
Limb sparing must always be performed in conjunction with chemotherapy. Recovery following surgery (without complications) takes about 3 months, though most dogs are using the limb within 10 days. Limb sparing (plus chemotherapy) does not improve survival times over amputation (plus chemotherapy), with median survival times of about one year reported.
Some dogs with osteosarcoma are not experiencing life-affecting pain from the leg at the time of diagnosis. In these cases, we will try and preserve limb function without removing the tumour for as long as possible. This is achieved using a combination of anti-inflammatory medications, and pain-relieving drugs. Infusions of drugs (bisphosphonates) that help prevent bone destruction by the tumour can also be given very 4-6 weeks. These bone-hardening drugs can provide very positive improvements in pain control for selected patients with bone cancer. Chemotherapy treatment may also be started during this time, to help slow progression of the metastatic disease.
Sadly, this period of relief may only last a few weeks or months, and development of unremitting pain will ultimately require a more definitive solution. However, this period allows the affected dog to maintain a largely normal quality of life. It may also aid in triaging patients who are primed to develop rapid progression of metastatic disease. From survival curve analysis, almost 30% of dogs will succumb within a few months of diagnosis due to progression of secondary disease irrespective of treatment strategies employed.
What other treatments are necessary?
It is generally considered that all osteosarcoma will have metastasised at the time of diagnosis, even though they are not detectable radiographically. For this reason, dogs that do not receive chemotherapy will usually die within a year of metastatic disease (median survival time, 3 months). Chemotherapy is employed for the treatment of dogs with no detectable secondary disease.
Carboplatin is the most commonly used agent in the treatment of canine osteosarcoma, though recent reports of cisplatin and doxorubricin suggest potentially equitable results.
The ideal dose regime has yet to be established. However, most authors agree that a minimum of four to six treatments with carboplatin should be given, at 21 to 28 day intervals. The first treatment should be given oonce the patient has recovered from surgery.
Removal of isolated pulmonary metastases has been performed in an effort to improve survival. Strict case selection was employed, and included: (1) primary tumour in complete remission, preferably for >300 days post-treatment; (2) one or two nodules only present on thoracic radiography; (3) cancer found only in the lung (i.e. no bone metastasis on bone scan); (4) lung nodules to have a long doubling time (>30 days) with no new visible lesions in this time. Although the concept of metastatectomy may be unpalatable to some, studies have demonstrated improvement in median survival times for the operated group to 487 days.