Specialty Spotlight: Clinical Approach to Lung Tumors in Dogs and Cats
March 20th, 2023 | Posted in General, Medical Articles
Clinical Approach to Lung Tumors in Dogs and Cats
Joseph Palamara, DVM, DACVS-SA
Surgery of the lungs is typically pursued to address acquired pulmonary diseases, including lung lobe torsion, consolidated lung lobes and abscesses, traumatic and spontaneous pneumothorax, and primary/solitary pulmonary neoplasia. Primary pulmonary neoplasia accounts for 1% of canine tumors and < 1% of feline tumors. Adenocarcinoma represents about 60% to 70% of feline lung tumors, whereas carcinomas account for up to 97% of primary lung tumors in dogs, with adenocarcinoma being more prevalent. 85% of canine primary epithelial pulmonary tumors (i.e., carcinomas) are bronchoalveolar in origin with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma trailing the remaining ~15%. Recently McPhetridge et al. JAVMA 2022 cited almost 10% of canine pulmonary tumors to be nonepithelial (sarcomas, neuroendocrine tumors). Most pulmonary tumors are diagnosed incidentally during general practice examination. Coughing tends to be the most commonly reported clinical sign in dogs with pulmonary neoplasia, with an incidence of 52% to 93%. Non-productive cough, exercise intolerance, lethargy, and weight loss have also been reported. A majority of pulmonary tumors are first diagnosed with plain film thoracic radiography, with a reported 83% of tumors visible in dogs. Solitary or multiple pulmonary masses are present in 67% to 91% of cats with primary pulmonary tumors. A comprehensive physical examination is recommended to identify any outward evidence of cutaneous/subcutaneous, oral, aural, osseous, and perianal evidence of primary neoplastic disease.
Diagnostic Workup for Pulmonary Tumors
Lung cancer is the primary cause of cancer-related human deaths worldwide, but primary lung cancer remains relatively uncommon in pet dogs and cats. Randomized controlled trials conducted from 1980 to 1990 concluded that screening with chest radiographs was not effective in reducing mortality of lung cancer in people. Chest radiography has been shown to be inferior to chest CT in terms of sensitivity but superior in terms of specificity in people. Those findings mirror our experience in veterinary medicine. Veterinary patients with suspect pulmonary nodules are typically recommended to undergo a full diagnostic workup to differentiate between primary and metastatic neoplasia. A minimum database (complete blood count, serum biochemistry, and urinalysis) is helpful for patient evaluation before anesthetic measures and to identify the presence of comorbidities as patients’ average age approaches 11-13 years in most studies. Pleural effusion is noted with more frequency in cats than dogs, approaching up to 30% of cases based on reports. When present, a sample should be acquired and has been shown to be diagnostic in up to 50% of cases. Bronchoalveolar lavage (BAL) has also been advocated as a method of diagnosis, showing either definitive or supportive evidence in 85% of dogs in a retrospective study most likely associated with a high incidence of bronchoalveolar origin of many canine primary epithelial lung tumors.
Advanced imaging is advised for local and distant staging of the thorax and abdomen for patients with pulmonary tumors, given the high frequency of malignant primary and secondary tumors, including ultrasound (US), computed tomography (CT), and positron emission tomography (PET). In our practice, thoracic CT is a preferred means for staging potential surgical candidates for a variety of reasons. CT has been shown to be more sensitive than radiography for the detection of pulmonary nodules. Local evaluation of pulmonary tumors is performed using thoracic CT, helping first classify tumors, i.e., multifocal, disseminated, solitary, invasive, and/or metastatic. Additionally, locoregional lymph nodes and primary sites of neoplasia are investigated using pre-contrast and contrast CT. US-guided fine-needle-aspirate (FNA) can be combined with thoracic CT procedures if intent for preoperative diagnosis of lung tumors or interest in further diagnostic workup is needed with the identification of a primary extra-pulmonary source for neoplasia. Acquired samples are submitted for formal laboratory cytopathologic assessment. Advantages to pretreatment sampling include: providing additional support for neoplasia for owner decision-making or suspicion for metastatic neoplasia. Older data (1990-2000s) demonstrated a low diagnostic yield for transthoracic FNA and high mortality rate, with the exception being for round-cell malignancy. Practically speaking, if metastatic disease is deemed less likely on staging findings, lung tumor removal is the next logical recommendation. Surgical planning is also achievable through multiplanar reconstruction (MPR) with thoracic CT. The size of the tumor (<5 cm), lymph node involvement, and clean margin at the time of surgery have been established as determinants for long-term outcomes in dogs with primary lung tumors and may also help identify patients as candidates for minimally invasive techniques via thoracoscopic surgery (video-assisted thoracoscopic surgery/VATS). Thoracic CT has been shown to be more accurate than thoracic radiographs in assessment for tracheobronchial lymph node (TBLN) metastases. TBLN lymphadenopathy in patients with pulmonary neoplasia has been shown to significantly shorten survival times in patients, reducing median survival time (MST) on average from 452 days to 26 days. MST of 5.5 months was shown in dogs with positive TBLN metastases in a recent contemporary cohort of cases. Masses > 5cm have also been shown to be a negative prognostic indicator in dogs. Patients with masses < 5cm may be more amenable to thoracoscopic surgery but still require a mini-thoracotomy to remove the mass from the chest cavity, as morcellation is not commonly utilized in veterinary surgery. Locations of lung tumors near the hilus create considerations for the ability for clean margin resection with complete pneumonectomy, whereas more distal tumors may be amenable to partial lung lobectomy.
Surgical Removal of Pulmonary Tumors
A variety of techniques are available to allow for competent thoracic exposure using open techniques or minimally invasive surgery with the utilization of small cameras, vessel-sealing devices (VSD), loop ligatures, and linear stapling equipment (ex., Endo-GIA or Thoracoabdominal/TA stapling devices). VATS is an attractive technique for lung surgery as minimally invasive surgery (MIS) often translates into faster recovery, fewer complications, shorter hospital stays, less pain, and avoids morbidity associated with open surgery especially cutting through the sternum. Minimally invasive surgery is available at Upstate Veterinary Specialties for patients meeting specific criteria involving tumor size (< 5cm for avg sized dogs; < 3cm in cats) and patient size, etc. Unfortunately, not all patients are candidates for MIS approaches. Alternatively, open chest surgery utilizing approaches between ribs (thoracotomy) or sternum (median sternotomy) can be performed as indicated with excellent results. Conversion rates for thoracoscopic lung lobectomy are between 9% to 23%, and is most commonly performed due to poor visualization. At surgery, the involved lung is freed from attachments, including the pulmonary ligament (for caudal lung tumors); in the minimally invasive theater, pulmonary ligaments are often ligated and transected using VSD (i.e., Ethicon Ligasure). Once mobile and based on preliminary staging, CT decision-making confirms intent at partial or complete lung lobectomy. Automatic stapling equipment is very useful at producing a rapid and consistent ligation +/- transection of normal lung tissue in accordance with wide-margin excision of pulmonary tumors. Linear staplers come in a variety of sizes, staple rows, and heights, releasing interlaced rows of staples into the tissue to create a “cross-stitching” to achieve the elimination of blood and airflow. In cases with hilar tumors, hand suturing/suture ligation can be a preferable technique to control tumor-free margins as well as allow for individual ligation of large cardiopulmonary vessels and bronchi. After partial or complete lung removal, patients are assessed for control of cardiopulmonary hemorrhage and bronchial air leakage – simple thoracic lavage and observation of blood or air leakage during manual ventilation is observed. Additional sutures, hemoclips, or staples may be used to control areas of concern. Next, tracheobronchial lymph nodes are investigated, either by incisional or excisional biopsy, to better determine the presence or absence of local extension of primary pulmonary disease. These lymph nodes can be located left, central, or right of the trachea/carina. Minimally invasive surgery has the benefit of magnification, allowing for the extirpation of small lymph nodes. Nonpublished communication and personal experience have supported the removal of lymph nodes as prognostic indicators, as it is still possible that tumor cells can be present in normal-sized lymph nodes. In humans, endobronchial ultrasound with transbronchial needle aspiration (TBNA) is considered part of a comprehensive evaluation of the extension of malignant disease deemed more sensitive than imaging modalities. After lung removal and TBLN sampling, a thoracostomy tube is placed, and surgical site(s) are routinely closed. The thoracostomy tube is evacuated to reestablish negative pressure to allow the return to spontaneous lung function, postoperative monitoring for hemorrhage or air production, and temporary removal of persistent pleural effusion. Our facility utilizes multimodal pain management for all surgical cases. Particularly, chest cases will receive a variety of constant-rate infusion (CRI) or intermittent medications to provide pain relief during surgery which also helps lower gas anesthesia requirements. Local anesthetics are utilized as intercostal nerve and local skeletal muscle blocks to reduce local pain sensation. Advanced techniques for locoregional anesthesia (ex., ultrasound-guided serratus plane block) have been reported with the use of nerve stimulators and musculoskeletal ultrasound to provide areas of direct blockade. Local anesthetics like bupivacaine are often used with effects limited to up to 8 hours. Nocita, an extended-release liposomal bupivacaine injectable suspension, provides long-acting local control of pain for up to 72 hours. Due to its high costs, the usage of dexmedetomidine in combination with bupivacaine is equally efficacious to shorten the onset for sensory and motor blocks and prolong the duration of action. Postoperative intravenous and oral analgesia, in combination with thermotherapy, round out the conscious efforts to provide comfort for pain during the postoperative recovery. Patients are typically hospitalized for 12-72 hours, followed by removal of low trending productive thoracostomy tubes and discharge from the hospital. All tissues are submitted for histopathology. It is important to submit the entire gross lung/tumor sample to allow for a comprehensive evaluation of surgical margins.
The prognosis for dogs diagnosed with primary pulmonary tumors depends on multiple factors, including clinical signs, tumor-specific factors (e.g., size, histologic subtype, grade), and World Health Organization (WHO) tumor node metastasis (TNM) clinical stage designation. Literature referring to histologic type has shown the improved survival for samples exhibiting papillary adenocarcinomas. Some reports have shown inaccuracies of the presurgical clinical stage based on diagnostics performed when limited to radiography; as discussed, this is expected as radiography has a low sensitivity for evaluation of lymph node status, multifocal disease, and tissue invasion. As forementioned, CT is our current preference for staging given the sensitivity for identification of pulmonary and lymph node involvement as well as detection of primary disease in extrathoracic locations.
In one clinical study of 67 dogs undergoing the removal of primary lung tumors, the overall MST was 361 days. Dogs with clinical signs associated with a primary lung tumor had an MST of 240 days compared with 545 days for asymptomatic dogs. Dogs with single solitary lung tumors (T1 clinical stage) had an MST of 790 days, which was significantly longer than dogs with multiple lung tumors (T2 clinical stage, 196 days) and dogs with lung tumors invading adjacent structures (T3 clinical stage, 81 days). Finally, the MST for dogs with grade I lung carcinomas was 790 days, significantly longer than the MSTs of 251 days and 5 days for dogs with grade II and III lung carcinomas, respectively. Metastasis often occurs through the lymphatics because most lung tumors are derived from epithelial tissue; however, vascular and intra-airway spread has also been reported. Historically, lymph node metastasis has been highly associated with significantly shorter survival, often prompting costly adjunctive treatment that may result in morbidity. Because many patients with high-grade tumors will ultimately develop metastatic disease following surgery, chemotherapy is commonly recommended. Previous reports have suggested a survival of only 26 to 131 days in dogs with lymph node metastasis. A recent retrospective showed no difference in survival times for dogs with or without nodal involvement receiving chemotherapy. The lack of standardized treatment protocols, case selection bias, and inconsistent follow-up has made it difficult to determine the outcome of dogs receiving adjuvant chemotherapy.
In summary, dogs with small, low-grade (well-differentiated) tumors without lymph node involvement have been reported to have an average survival time of 16 months or longer with surgery alone. Dogs with high-grade (poorly differentiated) tumors with lymph node involvement have an average survival of two to three months, even with surgery. Follow-up with a medical oncologist is warranted to review adjuvant treatment options.
– Joseph Palamara, DVM, DACVS-SA