Section 1: Overview of Common Cancers

Anal sac carcinoma

• Locally aggressive; complete excision is difficult owing to proximity to anal sphincter. Metastatic rate is highly variable: <40% to >90%. LN metastasis is seen more commonly and earlier than systemic (liver, bone, pelvis, lung) metastasis.
• Often slowly progressive unless diffuse metastasis is present at diagnosis or renal function is compromised from hypercalcemia.

• 3-view thoracic radiographs
• AUS +/− abdominal/ thoracic CT scan
• Ionized calcium

Primary tumor

• Surgery with preservation of fecal continence is the best first option.
• Lymphadenectomy is an adjunct surgical approach for suspect/ confirmed abdominal LN metastatic disease.
• Primary RT (palliative or curative intent) can provide good local control for unresectable disease.

Systemic treatment

• Unproven survival benefit
• Carboplatin-based chemotherapy
• Mitoxantrone-based chemotherapy
• Toceranib phosphate
• NSAIDs
• Metronomic chemotherapy
• Bisphosphonates for hypercalcemia

• Hypercalcemia
• Systemic (non-nodal) metastasis
• Primary tumor size >10 cm³

Lymphoma [Multicentric (lymph node, liver, spleen), skin, mucocutaneous, central nervous system, bone, bone marrow, GI, mediastinal]

• Considered a systemic disease, except for epitheliotropic lymphoma, which may be localized to primary sites (oral, skin) and some extranodal sites.
• All forms of lymphoma have the potential to be disseminated. Some forms may be indolent and slow to progress (spleen or node).
• ATLS is associated with extensive tumor burden.

• Immunophenotyping
• Histopathology as indicated (inconclusive cytology, solitary node, slowly enlarging LNs, desire for more detailed histological information)
• 3-view thoracic radiographs
• Advanced imaging (CT/MRI if CNS involvement is suspected)
• AUS

Systemic treatment

• Prednisone alone
• Single-agent chemotherapy
• Multiagent chemotherapy
• CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) protocol
• +/− stem cell transplantation
• +/− half-body RT
• Rabacfosadine
• Verdinexor

Prednisone alone

• MST ~1–2 mo

CHOP protocol

• MST ~1 yr
• Bone marrow transplantation and half-body RT may have an added survival benefit, but length of time is unknown

Single agent

• Highly variable response and durability, MST <1 yr

Rabacfosadine

• MST ~6 mo

Verdinexor

• MST ~2 mo

• T-cell phenotype
• Stage V (extra nodal, bone marrow, GI)
• Substage b (sick)
• High grade, blastic

Mammary gland cancer

• OVH before first estrus dramatically reduces risk. Risk rises rapidly with additional cycles.
• Individual tumors may progress from benign to malignant; the likelihood of malignancy increases with tumor size; dogs may present with multiple tumor types.
• Metastatic rate of malignant tumors is likely <50%.

• Primary tumor FNA (may be helpful in ruling out non– mammary gland tumors)
• 3-view thoracic radiographs
• Regional LN FNA

Primary tumor

Single malignant tumors: wide surgical excision with ~2-cm margins +/− deep fascia. Consider chain mastectomy (unilateral vs staged bilateral chain mastectomy) for dogs presenting with multiple tumors or developing multiple tumors over time.

Systemic treatment

• ROVH concurrent with or within 2 yr before tumor removal may improve survival in a subset of dogs. Studies of various chemotherapy protocols have not definitively established a benefit.

• MSTs range widely for malignant tumors.
• Consider the 50:50:50:50 rule: ~50% are benign, ~50% are malignant. Of the malignant tumors ~50% can be “cured” with appropriate surgery and ~50% will metastasize.

• Large tumor size
• Skin ulceration
• LN/distant metastases
• High histologic grade
• Histologic vascular or lymphatic invasion
• Lack of hormone receptor expression
• Sarcomas and inflammatory carcinomas are associated with poorer outcomes than carcinomas.

Mast cell tumor [Skin and subcutaneous tissues]

• Locally invasive; invasiveness increases with grade.
• Metastatic potential (Patnaik system):
• Grade 1: metastases are rare
• Grade 2: ~20%
• Grade 3: 50-100% Tumors may secrete histamine and heparin.

• Pretreatment staging is optional for small tumors exhibiting slow growth. Biopsy to determine histologic grade is advisable for any unresectable, large, or rapidly growing tumor.
• FNA cytology of regional LN.
• AUS and FNA of spleen or liver if enlarged; if LN metastases or systemic signs are present; or if known grade 3 tumor.

Primary tumor

• Surgical excision with 2-cm or proportional margins wide (lateral margins equivalent to the widest measured diameter of the tumor) and 1 fascial plane deep. Wider margins may be necessary for highgrade tumors.
• Scar excision may be considered if margins are histologically incomplete.
• RT may be considered if adequate margins cannot be achieved or margins are histologically incomplete.
• Tigilanol tiglate injection

Systemic treatment

• Vinblastine-based chemotherapy
• CCNU
• TKIs
• Gilvetmab

Ancillary therapy

• Consider H1 and H2 blockers for patientswith large tumors and/ or GI signs.

Primary tumor

• Grade 1 tumors and most grade 2 tumors are likely to be permanently controlled by appropriate surgery.
• When margins are histologically incomplete, local recurrence rates are ~20–30%.
• If wide margins cannot be achieved, RT provides 2 yr local control rates >85%.

Metastases

• Survival periods are highly variable. Prolonged MSTs and high 1 and 2 yr survival rates have been reported in ‘‘high risk’’ patients receiving prednisone and vinblastine.
• TKIs produce a meaningful response rate in grossly measurable tumors; survival data in patients at high risk for metastases have not been reported.

• Large tumors
• Higher histologic grades
• Advanced LN or distant metastases
• Mucous membrane locations
• High mitotic index, proliferation indices, microvessel density
• c-kit mutation
• Histologically incomplete surgical margins
• Local recurrence
• Systemic illness

Oral malignant melanoma

• Metastatic rate ~80%, LN then lungs.
• ~1/3 lack melanin and may be confused with sarcomas histologically.

• 3-view thoracic radiographs
• FNA of regional LN (even if normal size)
• Resection of medial retropharyngeal, parotid, and mandibular LN provides more complete staging.
• CT/MRI facilitate surgical planning, particularly for large and caudal tumors.

Primary tumor

• Surgery is generally the best first option. Mandibulectomy or maxillectomy is usually required, plus local LN excision.
• Adjuvant RT with coarse fractionation if resection is known or suspected to be incomplete.

Systemic treatment

• Oncept vaccination
• Carboplatin-based chemotherapy
• Gilvetmab

• Reported local recurrence rates after surgery alone range from 0-48%.
• Majority of measurable tumors treated with RT respond, and complete responses are common.
• Local recurrence rate of ~26% when RT is used to treat microscopic residual disease. Reported MSTs when surgery is included in treatment range from 5 to 17 mo. Carboplatin produces responses in measurable disease in 30–50% of patients; studies regarding prolongation of survival are conflicting. Studies regarding the ability of DNA vaccination to prolong survival are conflicting.

• Large tumor size, caudal location, and previous local recurrence are risk factors for local recurrence and survival after surgery or RT.
• Elevations in proliferation indices
• LN or distant metastasis

Osteosarcoma [Proximal humerus, distal radius, distal femur, proximal and distal tibia]

• >90% of dogs have pulmonary micrometastases on presentation, rare skeletal metastases.

Essential

• 3-view thoracic radiographs

Optional

• Bone scintigraphy or radiographic bone survey
• Thoracic CT
• AUS

Primary tumor

• Amputation, limbsparing surgery, or stereotactic RT
• Palliative RT

Systemic treatment

• Carboplatin- or doxorubicin-based chemotherapy

• Amputation alone: MST ~4 mo
• Amputation and chemotherapy: MST ~10–12 mo

• Elevated serum ALP
• Proximal humeral location

Soft tissue sarcoma: mesenchymal tumors including fibrosarcoma, peripheral nerve sheath tumor, and others [Skin and subcutaneous tissues]

• Locally invasive; invasiveness increases with grade.
• Overall metastatic rate is ~20% and increases with grade: Grade 1 and 2 ~15%, Grade 3 ~50%. Clinically apparent metastases develop relatively late (median ~1 yr).

• 3-view thoracic radiographs
• CT/MRI may facilitate surgery for large or fixed tumors and tumors adjacent to key anatomic structures.

Primary tumor

• Surgical excision with >3 cm margins including a fascial plane below if possible. Amputation may be considered if adequate margins cannot be provided. Scar excision may be considered if margins are histologically incomplete.
• RT may be considered if adequate surgical margins could not be provided or margins are histologically incomplete.
• Metronomic chemotherapy may improve duration of local control.

Primary tumor

• When margins are histologically incomplete, local recurrence rate is ~20–35%. Recurrence rates are likely higher for high grade tumors.
• RT for incompletely resected tumors provides local control rates: 75% at 1 yr; median time to local recurrence ~2 yr.^a

Systemic disease

• Doxorubicin and other agents are known to produce responses in measurable disease. Data regarding treatment of micrometastases with conventional or metronomic chemotherapy are lacking.

• Local recurrence
• Incomplete histologic margins
• Large tumors
• Metastases
• High mitotic index/grade

Splenic hemangiosarcoma Note: Some splenic masses are benign hematomas and cannot be definitively distinguished from HSA before splenectomy and biopsy.

• Metastatic rate approaches 100%.
• Liver is the most common metastatic site.
• Survival times are highly correlated with clinical stage:
  • Stage 1: No hemoabdomen; no clinically detectable metastases.
  • Stage 2: Hemoabdomen, no clinically detectable metastases.
  • Stage 3: Clinically detectable metastases.

Essential

• AUS for intraabdominal metastases. Liver metastases cannot be definitively distinguished from hyperplastic nodules.
• 3-view thoracic radiographs

Optional

• Echocardiography for concurrent right atrial mass; present in ~9% of dogs presenting for splenic HSA.

Primary tumor

• Splenectomy with biopsy of liver nodules

Systemic treatment

• Doxorubicin-based conventional chemotherapy and/ or metronomic chemotherapy

• Splenectomy alone: MST ~1.5–3 mo
• Adjuvant chemotherapy: MST ~3–6 mo

• Clinical stage

Transitional cell carcinoma/ urothelial carcinoma [Urinary bladder, urethra, prostate]

• Aggressive with tendency for local invasion and metastasis to regional LNs and lungs, high risk of urinary tract obstruction.

• Physical examination to include rectal exam
• 3-view thoracic radiographs
• AUS
• Cystoscopy
• Diagnostic catheterization
• BRAF gene mutation test

• NSAIDs: piroxicam
• Chemotherapy: mitoxantrone, carboplatin, vinblastine
• Intensity-modulated RT

• NSAIDs alone: MST ~6 mo
• NSAIDs with chemotherapy: MST ~12 mo
• Intensity-modulated RT, NSAIDs, and chemotherapy: MST ~15-18 mo

• Clinical stage

Nasal tumors [Carcinoma, adenocarcinoma, squamous cell carcinoma, osteosarcoma, fibrosarcoma, undifferentiated sarcoma, lymphoma]

• Local invasion/ destruction with risk for regional and distant metastasis.

• 3-view thoracic radiographs
• LN cytology
• CT/MRI
• Biopsy

• RT
• Chemotherapy: carboplatin, doxorubicin, NSAID (palliative)
• Toceranib

• RT: MST ~6-18 mo
• Surgery or chemotherapy alone: MST ~3-6 mo

• Clinical stage
• Squamous cell carcinoma

Lymphoma [Mediastinum, gastrointestinal, liver, spleen, kidney]

• Considered a systemic disease except for rare solitary sites (e.g., nasal or skin lymphoma, which can be localized). Some forms may be indolent and slow to progress (e.g., spleen, lymph node, small cell lymphoma).

• FeLV/FIV testing
• 3-view thoracic radiographs
• AUS
• Advanced imaging (CT/MRI if suspected CNS involvement)
• Immunophenotype not critical in feline lymphoma

• Prednisolone alone
• Prednisolone/ chlorambucil (low-grade GI)
• Single-agent chemotherapy: CCNU (lomustine)
• Multiagent chemotherapy: COP (cyclophosphamide, vincristine, prednisolone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)
• RT

Prednisolone alone:

• MST ~2–3 mo
• Single agents: highly variable response and durability but MST ~4–6 mo

CHOP protocols:

• MST ~6–9 mo
• Nasal lymphoma may have >2 yr controls with RT
• Low-grade GI 8 mo to >2 yr

• FeLV+
• Grade/large cell
• Stage
• Substage b; most cats are b

Mammary gland cancer

• Incidence of feline mammary tumors is dependent on when OVH is performed. Cats who undergo OVH prior to 6 months of age have a 91% reduced risk of developing mammary cancer.
• Locally aggressive.
• Highly metastatic (80–90% to nodes, liver, lungs).

• 3-view thoracic radiographs
• AUS
• Regional LN FNA (even if normal size)
• CT/MRI for surgical planning

Primary tumor

• Surgery if possible. Unilateral radical mastectomy with regional node removal or staged bilateral radical mastectomy with 1 mo between sides (simultaneous bilateral not recommended)

Systemic therapy

• Chemotherapy value uncertain (doxorubicin, carboplatin, toceranib)
• NSAIDs

• Guarded to poor prognosis.
• Tumor size: <2 cm MST >3 years
• Tumor size: >3 cm MST 4-12 mo
• Surgery +/- chemotherapy: MST ~1 yr

• Tumor size >3cm
• Lymphatic invasion
• Higher clinical stage
• High histologic grade
• HER2 expression

Squamous cell carcinoma [Oral (mandible, maxilla, sublingual, gingival), retrobulbar, oropharynx, cutaneous, nasal planum, ear pinna, multifocal cutaneous in situ (Bowens)]

• Locally aggressive.
• Low metastatic rate.
• Oral tends to be extremely aggressive.
• Cutaneous is often slowly progressive.

• 3-view thoracic radiographs vs thoracic CT
• Regional LN aspirate (even if normal size)urgical or RT planning
• Biopsy
• CT scan vs skull/ oral radiographs
• CT/MRI for surgical or RT planning

Oral primary tumor

• Surgery if possible (small rostral lesions, but variable outcomes with eating).
• Adjuvant RT if resection is known or suspected to be incomplete.
• Primary RT (palliative or curative intent) provides poor local control for unresectable disease even if combined with chemotherapy.

Systemic treatment (unproven survival benefit)

• Carboplatin
• Mitoxantrone
• Toceranib phosphate
• NSAIDs
• Metronomic chemotherapy
• Bisphosphonates (zoledronate, pamidronate and others) may help with bone integrity.

Cutaneous primary tumor

• Surgery, if possible, provides the best chance for cure.
• Adjuvant RT if resection is known or suspected to be incomplete.
• Strontium (for very superficial lesions).
• Photodynamic therapy, electrochemotherapy are local options.
• Topical imiquimod for early superficial lesions.

Oral

• MST ~ 3–6 mo

Cutaneous

• Outcome associated with stage.
• Early superficial lesions can be cured.
• Bulky invasive lesions often cannot be surgically removed, rendering RT outcomes much more guarded.

• Oral location
• Stage
• Invasion beyond basement membrane (cutaneous)

Soft tissue sarcomas (including injection site sarcoma) [Cutaneous and subcutaneous tissue, interscapular, hind limb, flank]

• Locally aggressive, especially injection site, with high (>50%) local recurrence.
• Non-injection site sarcoma is less aggressive and location and grade dependent. Metastatic rate is <10% for low grade, non– injection site.
• Metastatic rate >25% for high grade and/or injection-site sarcoma.

• CT/MRI for surgical and RT planning
• Biopsy
• +/- 3-view thoracic radiographs and AUS

Primary tumor

• Surgery, if possible, is the initial treatment of choice. Preoperative radiation should be considered if gross disease is in a complex anatomic location. Adjuvant RT if resection is known or suspected to be incomplete.
• Primary RT alone provides poor local control for unresectable disease but can provide palliation of signs.

Systemic treatment

• Doxorubicin
• Carboplatin
• NSAIDs
• Metronomic chemotherapy

Injection site sarcoma

• Median DFI <12 mo for wide surgery alone, even shorter for larger, more marginally excised tumors. Surgical cures possible with radical surgery (amputation or hemipelvectomy).
• MST 1–2 yr with surgery and RT (pre - or postoperative) or surgery and doxorubicin.

• Injection-site location
• Size ≥2 cm
• Mitotic index >6
• Incomplete surgical excision
• Malignant fibrous histiocytoma histology

Nasal tumors [lymphoma, carcinoma, adenocarcinoma]

• Local invasion/ destruction with risk for regional and distant metastasis.

• FeLV/FIV testing
• 3-view thoracic radiographs
• AUS
• CT/MRI
• Biopsy

• RT
• CCNU (lomustine), COP or CHOP for lymphoma
• NSAID/carboplatin for carcinoma

• MST 1–2 yr or normal lifespan for lymphoma
• MST ~6–15 mo for carcinoma/ adenocarcinoma

• Clinical stage

Mast cell tumor [Visceral, cutaneous (head, neck, trunk, limbs)]

Intestine

• Aggressive with metastasis to mesenteric LN and liver ± spleen, lung, and bone marrow.

Visceral organ

• Reported in ~20% of cats with cutaneous MCT.^a,b,c

Skin

• Mastocytic: generally benign.

• AUS
• FNA
• Biopsy

• Surgery +/- chemotherapy with anecdotal efficacy
• Medical therapy alone (lomustine, toceranib) associated with response rates >50%

Intestine

• MST ~6 mo (one study has reported median survival times of 17+ months)^d

Spleen

• MST ~ 1-2 yr

Skin

• Generally benign with excellent prognosis

• Clinical stage
• Histologic grade
• Anorexia
• Weight loss