Page 497 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 23 Cancer of the Gastrointestinal Tract 475

enlarged LNs, 611,617 or perianal region and regional lymphatic Overall, the reported MSTs for dogs with AGASAC range from
chain regardless of the size of the regional LNs. 609,617 These dif- 386 to 960 days, 564,599–603,605–607,609–611,615,616 with estimated 1-
Tumor-
600
and 2-year survival rates of 65% and 29%, respectively.
ferences could affect clinical outcomes and should be considered
VetBooks.ir when studies are compared. There may be a role for RT in the related deaths vary widely between studies, with 41% to 81% of
600,601,605,606
curative-intent management of dogs with incompletely excised
dogs dying as a result of AGASAC.
AGASAC or dogs with surgically excised regional LN metasta- The prognosis for dogs with AGASAC is dependent on a
sis, or in the palliative management of dogs with measureable number of factors, especially clinical stage. In one study, dogs
disease 600,601,609,619 ; however, further studies are required to with no metastasis and primary tumor size less than 2.5 cm
determine how RT should be optimized. treated with surgery alone had overall favorable outcomes with
The majority of published studies have not standardized ther- the MST not reached and with only 9% of dogs experiencing
apy for AGASAC according to clinical stage, and there is some tumor-related deaths. 601 In other studies, dogs with LN metas-
evidence that the treatment approach may be stage dependent. 601 tasis treated surgically, with or without adjuvant chemotherapy,
In one study, a clinical stage system and treatment algorithm were had significantly shorter OSTs compared with dogs without
developed on the basis of a retrospective analysis of 80 dogs, and metastasis. 605–607 OST was 293 to 448 days in dogs with LN
then these were evaluated in a prospective cohort of 50 dogs. 601 metastasis and 529 to 925 days in dogs without metastasis. 605–607
The proposed treatment algorithm included various combina- In a study of 28 dogs with advanced LN metastasis (larger than
tions of surgery, carboplatin chemotherapy, and hypofractionated 4.5 cm), treatment with hypofractionated RT resulted in a bet-
RT. However, this staging system has not been widely accepted, ter median PFI and MST (347 days and 447 days, respectively)
likely because it does not prioritize surgical excision on the basis of than did surgery with extirpation of metastatic LNs (159 days
resectability. Surgery, according to the algorithm, is recommended and 182 days, respectively). 611 Based on these collective find-
only for primary tumors smaller than 2.5 cm and for metastatic ings, the role of a stage-dependent treatment algorithm is attrac-
LNs smaller than 4.5 cm when the primary tumor is smaller than tive and may become a future direction in the treatment of dogs
2.5 cm. In light of the increasing evidence of the importance of with AGASAC.
surgery in the treatment of AGASAC and its positive effect on sur- Poor prognostic factors reported in various studies include pri-
vival, 600,601,605–607,612,637 surgical excision, including resection of mary tumor size, 600,601,607,617 presence of clinical signs, 607 pres-
recurrent disease, has become the mainstay of treatment for resect- ence of LN metastasis, 601,605–607 size of LN metastasis, 601 presence
able AGASAC irrespective of size. Further studies are required to of distant metastasis, 600,601,624 nonpursuit of surgery, 600,601 treat-
investigate the optimal combinations of surgery, chemotherapy, ment with chemotherapy alone, 600 lack of any therapy at all, 601
and RT in the management of dogs with various clinical stages of histologic features of the primary tumor, 607,608 E-cadherin immu-
AGASAC. noreactivity, 624 and, in some studies, hypercalcemia. 600,602,607
Tumor size is prognostic for survival in a number of stud-
Prognosis ies, but the threshold varies. 600,601,606,615,616 In one study of
113 dogs, dogs with tumors less than 10 cm had a better MST
2
2
Although dogs with metastatic AGASAC are rarely cured, long- (584 days) than dogs with AGASAC greater than 10 cm (292
term survival may be achieved in many cases after surgery-based days). 600 In another study, a maximal tumor dimension of 2.5
treatments of the primary tumor and metastatic LNs both at pre- cm was found to be prognostic. 601 In the retrospective arm of
sentation and in the face of recurrence. The reported DFIs for this study, the MSTs were 1205 and 722 days for dogs with non-
dogs treated surgically, with or without adjuvant therapy, range metastatic AGASAC less and greater than 2.5 cm, respectively. 601
from 262 to 443 days. 605–607 Local recurrence rates vary widely In a study of 77 dogs treated with palliative-intent hypofraction-
from 5% to 44%. 603,605–607,612 Local recurrence is not associated ated RT, the only negative predictor for survival was tumor size
with completeness of excision, 603,607 and this highlights the dif- greater than 2.5 cm. 617 In another study, a tumor size of 2.5
ficulty in using the completeness of excision to determine whether cm was not predictive of survival in 39 dogs, but a 4-cm cutoff
adjuvant therapies, such as RT or revision surgery, are required was prognostic. 607 Dogs with AGASAC smaller than 4 cm had
after incomplete histologic excision. Metastasis to regional LNs a longer PFI and MST (518 and 773 days, respectively) than
and to distant sites after surgery has been reported in 31% to 69% dogs whose tumors were greater than 4 cm (251 and 433 days,
and 14% to 18% of dogs, respectively. 603,606,607,612 Multiple stud- respectively). These discrepancies in prognostic tumor size could
ies have reported shorter median DFIs in dogs with LN metasta- reflect differences in how tumors are measured, the difficulty in
sis at diagnosis (134–197 days) compared with dogs without LN using an absolute metric measurement across a wide range of dog
metastasis (529–760 days). 603,606,607 Dogs with LN metastasis at sizes and body weights, and/or the inherent difficulty in identify-
the time of surgery have a 2.5-fold hazard of disease progression ing consistent prognostic factors using nonstandardized cohorts.
compared with dogs without LN metastasis. 603 Tumor size was associated with the presence of clinical signs in
For dogs with either local recurrence or postoperative LN one study. 607 Dogs with clinical signs were more likely to have
metastasis, further treatment can improve STs. 606,610,637 In one local recurrence after surgery and shorter OSTs compared with
study of 74 dogs with AGASAC treated surgically, with or with- dogs diagnosed incidentally. 607 Compared with asymptomatic
out adjuvant chemotherapy, 55% developed either local recur- dogs or dogs with local signs, dogs with systemic clinical signs
rence and/or LN metastasis. 606 Of these dogs, 68% were treated (e.g., anorexia, polyuria/polydipsia, abnormal stool shape, tenes-
with additional surgery, RT, and/or chemotherapy. The MST for mus, constipation, and/or lethargy) had significantly shorter
dogs in which recurrent or metastatic disease was treated was 374 PFIs and OSTs. 607
days after treatment for progressive disease, compared with 47 Metastatic disease, both to the regional LNs and distant
days for dogs in which the recurrent or metastatic disease was not sites, is associated with a worse prognosis in dogs with AGA-
treated. 606 In another study, the additional MST associated with a SAC (Fig. 23.34). 600,601,605–607,624 The reported MSTs for dogs
second surgical intervention was 283 days. 612 with LN metastasis at diagnosis treated with various modalities