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Surgical outcomes in feline mammary adenocarcinoma

Gemignani F, Mayhew PD, et al.  Association of surgical approach with complication rate, progression-free survival time and disease-specific survival time in cats with mammary adenocarcinoma: 107 cases (1991-2014). J Am Vet Med Assoc. 2018 Jun1;252(11):1393-1402.

Mammary gland tumors in cats are relatively common, and unfortunately, in contrast to those in dogs and humans, over 80% are malignant.  These tumors may not be detected early because of the position of the mammary glands on the underside of the animal and the fact that they are usually hidden by the haircoat.  Often, a feline mammary tumor is finally discovered when the owner finds a wet spot on the ventral thorax or abdomen resulting from tumor ulceration.

This retrospective case series of 107 cats that underwent mastectomy surgery at referral hospitals in Europe, the United States, and Canada, reviews the outcome, including progression-free survival time, disease-specific survival time, and postoperative complications associated with various surgical strategies (unilateral mastectomy, staged bilateral mastectomy, and single-session bilateral mastectomy).

Mammary adenocarcinomas are aggressive tumors, being both locally invasive into the vasculature and surrounding tissues and metastatic to draining lymph nodes as well as more distant sites such as lungs, pleura, and liver.  Many treatments are available, including surgical excision, chemotherapy, radiation therapy, and immunotherapy, and sometimes these modalities are used in combination.  Frequently, however, regardless of therapeutic approach(es) employed, these tumors tend to recur or develop at new sites, and often are the cause of the cat’s death.  Outcome is known to improve if a full-chain (radical) mastectomy is performed regardless of tumor size instead of a regional mastectomy.  What is uncertain is whether  unilateral full-chain mastectomy, staged bilateral full-chain mastectomy, or single-session bilateral mastectomy will provide the best outcome for the patient, with minimal complications.  Another question is whether adjuvant treatments are helpful in cats who have undergone radical surgery.

These investigators hypothesized that progression-free survival times and disease-specific survival times would be increased in those mammary adenocarcinoma patients undergoing bilateral mastectomy rather than unilateral mastectomy.  Staged bilateral mastectomy procedures are usually performed several weeks apart. The group was also interested in learning if cats who had bilateral mastectomies, either staged or single-session, had more surgical complications than those undergoing unilateral mastectomy.  An additional area of investigation was to determine if adjuvant chemotherapy prolonged disease-free survival time in the patients. Only cats who had a complete medical record and had a full-chain unilateral or bilateral mastectomy for histopathologically confirmed mammary adenocarcinoma were included in the study.  Those animals who had a unilateral mastectomy but had bilateral disease or who had distant metastasis at the time of surgery were excluded from the investigation.

Based on clinical and diagnostic imaging findings, each cat was assigned a disease stage in accordance with the modified World Health Association TNM staging system.  In this system, tumor size (T), the presence or absence of spread to regional lymph nodes (N) and distant metastasis (M) are recorded.  The disease stage as evaluated by these criteria correlates with the prognosis. Smaller mass(es) and lack of evidence of spread to regional lymph nodes or distant metastasis implies a better prognosis.

Spayed females comprised 93% (99/107) of the included patients.  Five percent (6/107) were intact females, and 2 cats (2%) were neutered males.  Of the 99 spayed female patients, the type of sterilization procedure performed was known in 44:  64% (n = 28) had been ovariectomized only, while 36% (n = 16) had undergone ovariohysterectomy.  None of the cats had been treated with oral progestins.  There was a known parturition history in 44 of the patients; 11/44 (25%) had at least one pregnancy, while 33/44 (75%) were nulliparous. Over half (n = 58) of the cats were Domestic Shorthairs; 25 were Domestic Longhairs, 7 were Siamese, and 17 represented other pedigreed breeds.

Of the 107 patients, tumor location was reported in 103.  In 34 of the cats (33%), there were tumors in more than one site.  The fourth (inguinal) mammary glands were most commonly involved; tumors in this location were found in over half (n = 58; 56.3%) of the cats.  Tumors of the first (axillary) glands were present in 33 (32%) of the patients; 29 (28.2%) had tumors of the second (thoracic) glands, and in 40 (38.8%) the third (abdominal) gland was involved.   No evidence of distant metastasis was found  in any of the cats (93/107; 86.9%) that had three-view thoracic radiographs or in any cats (45/107; 42.1%) in whom abdominal ultrasonography was performed. Inguinal or iliac lymphadenopathy was found in 9/45 of the cats who had abdominal ultrasonography, however.

Unilateral mastectomy was performed in 61/107 (57%) of the animals.  Fourteen cats (13%) had staged bilateral mastectomy, while 32 (30%) underwent single-session bilateral mastectomy.  Despite differences in the extent of surgery, median procedure time for unilateral mastectomy (or first stage of bilateral mastectomy) was 70 minutes (range, 40-100 minutes), while that for single-session bilateral mastectomy was 72.5 minutes (range, 35-165 minutes).   Superficial inguinal lymph nodes were removed in 64 cats; both axillary and inguinal lymph nodes were removed in 29 cats, and 14 cats did not have any regional lymph nodes excised.  No significant differences in patterns of lymph node removal existed among the different mastectomy strategies.  Of the 93 cats who had regional lymph nodes excised, almost half (44.1%; n = 41) demonstrated evidence of lymph node metastasis.

On histopathologic evaluation, tumors from all 107 cats were identified as mammary carcinomas, and most were labeled adenocarcinoma.  As the study spanned 23 years in multiple institutions, histopathologic assessment was not uniform, and this made it impossible to further classify the tumors by histopathologic grade or subtype.  In 53% (57/107) of the patients, extent of tumor differentiation was identified:  21% (12/57) were well differentiated; 36.8% (21/57) were moderately differentiated, and 42.1% (24/57) were poorly differentiated. Lymphatic invasion was present in 43/107 (40.2%) of the animals, while vascular invasion was found in 16/107 (15.0%). Clean margins (> 2 mm) were found in 78 of the 95 cats (82.1%) for whom tissue margins were evaluated. Narrow margins (0-2 mm) were found in 11/95 (11.6%) of these patients, and incomplete excision was identified in 6/95 (6.3%) of cats.

Of the 107 patients in the study, 31 (29%) experienced postoperative complications.  Common complications included such events as infection, dehiscence, or seroma formation; other, rarer complications included abdominal herniation, respiratory failure, pleural effusion, and cardiac arrest. Only 3/107 patients died of causes related to postoperative complications. Bilateral mastectomy, especially single-session bilateral mastectomy, was significantly more likely to result in complications than unilateral mastectomy, but also resulted in substantially longer median progression-free survival time (542 days) than unilateral mastectomy (289 days).  Thirteen of 32 cats (40.6%) undergoing single-session bilateral mastectomy experienced complications, as did 5/14 cats (35.7%) who had staged bilateral mastectomy. Of the 61 cats who underwent unilateral mastectomy, postoperative complications occurred in 21.6% (13/61).

Adjuvant chemotherapy was administered to half of the cats following surgery (53/105; 50.5%); 28 of these patients had unilateral mastectomy, while 25 had bilateral mastectomy. Doxorubicin-based protocols were used in most of these animals (n = 46).

Almost 2/3 of the 105 cats that survived the immediate postoperative period (61%; n = 64) experienced progressive disease.  Of the 60 cats that underwent unilateral mastectomy, 28 had local recurrence, and 33 had regional or distant metastasis.  Of the 45 cats with bilateral mastectomy, 9 had local recurrence and there was regional or distant metastasis in 16.   In the final multivariable analysis, bilateral mastectomy was associated with significant extension of progression-free survival time, even when lymph node metastasis was present.  Factors in the multivariable model that increased the risk for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis at the time of surgery, and tumors present in the fourth (inguinal) mammary gland.  Although lymph node metastasis was associated with progressive disease, almost one-third of the cats (31.7%; 13/41) with this problem at the time of surgery did not progress to further metastasis.

Disease-specific survival time in the patient group was defined as time from mastectomy to tumor-related euthanasia or natural death.  The median disease-specific survival time for all study cats was 375 days; cats who underwent bilateral mastectomy had a median disease-specific survival time of 1,140 days, while among those who had unilateral mastectomy, the median disease-specific survival time was 473 days.  Factors strongly associated with tumor-associated death included development of regional or distant metastasis after surgery; among those cats who did not develop metastasis, treatment with unilateral mastectomy increased the risk of death.  Increased risk of death also was noted with lymph node metastasis at the time of surgery. Chemotherapy treatment was found to be beneficial in that it increased disease-specific survival time in those cats who received it.

This study has some significant limitations due to the length of time and number of institutions involved, leading to nonuniform histopathologic evaluation, varied monitoring and follow-up protocols, nonrandom allocation to treatment, and differing adjuvant chemotherapy treatments.  However, it demonstrates that cats with mammary adenocarcinoma will experience longer progression-free survival and disease-specific survival times when mastectomy is radical and bilateral and when adjuvant chemotherapy is given postoperatively.  Staging the bilateral mastectomy rather than performing this surgery in a single session is less likely to result in postoperative complications.  [PJS]

See also:

Morris J.  Mammary tumors in the cat:  size matters, so early intervention saves lives.  J Feline Med Surg. 2013;15:391-400.

Giménez F, Hecht S, et al. Early detection, aggressive therapy: optimizing the management of feline mammary masses.  J Feline Med Surg. 2010;12:214-224.