with incomplete margins are low (12–21%) (Thompson 2011; Gill et al. 2020). Mitotic index is a prognostic factor for local recurrence (Thompson 2011).
Postoperative Recommendations
Completely Excised MCTs
Grade I or II MCTs that are Kiupel low grade excised with complete surgical margins do not require any adjuvant therapy as the risk for local recurrence (5–11%) or metastasis is relatively low (Murphy et al. 2004; Séguin et al. 2001; Weisse et al. 2002; Michels et al. 2002). Patients should be evaluated regularly for signs of local recurrence and any new cutaneous masses should be thoroughly investigated. Grade III MCTs that are completely excised have a low chance for local recurrence but a high chance to develop metastatic disease. As such, these cases should receive adjunctive chemotherapy to delay or prevent metastatic spread. Kiupel high‐grade tumors have a local recurrence rate of 18–36%, even when margins are complete (Donnelly et al. 2015; Moore 2020).
Incompletely Excised MCTs
Incompletely excised grade I or II MCTs have a low chance of local recurrence and low chance of metastatic spread (Séguin et al. 2006). The surgeon has several recommended treatment options in the case of incompletely excised grade I or II MCTs, including monitoring, additional surgery, and adjuvant chemotherapy or radiation therapy. Murphy et al. concluded that dogs with well‐differentiated, incompletely excised tumors that did not receive adjuvant treatment did as well as those that did have additional therapy (Murphy et al. 2004).
The preferred treatment for incompletely excised MCTs, if possible, is excision of the surgical scar with a larger margin of normal tissue at least one fascial plane deep. If the anatomical location does not permit extensive resection, a more conservative re‐resection and/or adjuvant radiation therapy is indicated (Kry and Boston 2014; Karbe et al. 2021). One study evaluated the excision of surgical scars after 19 incompletely excised mast cell tumors and 4 mast cell tumors with close margins (tumor cells within 3 mm of a surgical margin (Kry and Boston 2014). Local recurrence occurred in 13% of these cases whereas local recurrence occurred in 38% in a group where no further treatment was performed. Tumors where the scar was re‐excised had longer median time to local recurrence and dogs with a re‐excision had a longer median survival time than dogs and tumors with no further treatment. Presence of microscopic disease was found in 48% of scars and was not prognostic for local recurrence (Kry and Boston 2014). In a more recent study, scar revision (i.e. re‐excision) of 86 mast cell tumors that had been excised with tumor cells at the margins (87% of the tumors), margins of <1 mm (8%), or margins of 1–3mm (5%), local recurrence occurred in 4% of the scars revised (Karbe et al. 2021). Residual mast cell tumor was found in 27% of the resected scars. Following scar revision surgery, complete margins were achieved in 92% of tumors. Margin status and presence of mast cell tumor in the resected scar were not associated with local recurrence or disease progression but grade III tumors were more likely to develop local recurrence, regional lymph node metastasis, or any disease progression (Karbe et al. 2021).
Incompletely excised grade III MCTs have a high chance of both local recurrence and metastatic spread. These cases should receive additional local therapy (either additional surgery or radiation therapy), as well as chemotherapy (Hahn et al. 2004).
Local Tumor Recurrence
Séguin et al. (2006) found that dogs developing local recurrence after surgical excision had shorter survival times than dogs without local recurrence, with incompletely excised grade II MCTs.
Another study showed histopathological tumor‐free vs. non‐tumor‐free margins were not associated with a different frequency of tumor‐related death; however, significantly more dogs in the nontumor‐free margin group relapsed by 12 and 24 months postoperatively compared to the tumor‐free margin group (Michels et al. 2002).
Radiation Therapy for MCT
Radiation therapy can be used as part of multimodal therapy either as an adjunctive therapy after incomplete surgical MCT excision or as a primary treatment modality of the primary tumor and/or regional lymph node(s). Radiation is most effective and most commonly used as an adjunctive therapy after surgical removal or tumor size reduction to a microscopic level (LaDue et al. 1998). When possible, surgery should be performed prior to radiation therapy to decrease the tumor volume, as dogs treated with adjuvant radiation therapy with smaller tumor volumes have longer disease‐free intervals than those with larger tumor volumes (LaDue et al. 1998; Hahn et al. 2004). The risk of systemic effects because of MCT degranulation is present in tumors treated with radiation of macroscopic disease, so pretreatment with prednisolone is recommended (Dobson et al. 2004).
Radiation therapy is very effective at eliminating residual microscopic disease after incomplete excision of grade I and II MCTs. Local tumor control rates of 86–94% at two and three years are reported after adjunctive radiation therapy for incompletely excised grade II MCTs (Frimberger et al. 1997; al‐Sarraf et al. 1996; Poirier et al. 2006). These rates are similar to the local tumor control rate of 89% achieved with complete surgical excision of grade II MCTs (Weisse et al. 2002). Radiation therapy for incompletely excised grade III, stage 0 MCTs, is encouraging compared to untreated incompletely excised grade III MCTs with a one‐year local control rate of 65% and one‐year survival rate of 71% (Hahn et al. 2004).
If the regional lymph node is positive for MCT disease (stage II disease), radiation therapy of the affected lymph node has been advocated by some investigators to improve survival time. A study by Poirier et al. found no difference in overall survival rate, whether the regional lymph node was prophylactically irradiated or not (Poirier et al. 2006).
Palliative radiation using 4 × 8 Gy fractions at weekly intervals has been reported as a treatment option for unresectable MCTs alone or in combination with chemotherapy (Dobson et al. 2004).
Electrochemotherapy
Electrochemotherapy is a local ablative treatment modality that uses direct delivery of electric pulses to change cell membrane permeability to enhance the intracellular accumulation of intra‐tumoral or intravenous injection of cytostatic drugs (most commonly bleomycin). Electrochemotherapy has been shown to be effective for local control of canine MCTs either as a sole treatment or in combination with surgery and should be considered as another local treatment option, especially for MCTs located on the limbs (Lowe et al. 2017).
Chemotherapy for MCT
The use of adjuvant chemotherapy is indicated after resection of grade III or Kiupel high‐grade MCTs because of their high metastatic rate and for metastatic and unresectable MCTs. The use of chemotherapy after incomplete resection of grade I and II MCTs and Kiupel low‐grade MCTs is not indicated based on their lower metastatic potential.
Some of the chemotherapeutic agents that have reported activity against canine MCTs are prednisolone, vinblastine, CCNU (Lomustine), vinorelbine, and chlorambucil.
The response rate of macroscopic cutaneous MCTs to oral prednisolone as a single agent is reported to be 20% (McCaw et al. 1994). Most of these responses were partial responses with remission times between 10 and 20 weeks.
The reported response rates for single‐agent vinblastine range from 12 to 27% (Rassnick et al. 2008). Vinblastine is commonly administered to dogs at a dosage of 2.0 mg/m2. The dose can be escalated to 3.0–4.0 mg/m2 with neutropenia as the dose‐limiting toxicity (Vickery et al. 2008; Bailey et al. 2008).
CCNU (Lomustine) is an antitumor alkylating agent in
