Oncological Treatment Options: Indications and Contraindications

Definition / Overview

Surgical oncology sits at the intersection of oncological principles and technical surgery. A consultant-level understanding demands more than knowing what options exist - it requires the ability to synthesise patient fitness, tumour biology, anatomical considerations, and evidence-based protocols to recommend the right treatment, in the right sequence, for the right patient. Core modalities include:

• Surgery (curative, cytoreductive, palliative)
• Systemic therapy (conventional cytotoxic chemotherapy, targeted/biological agents, immunotherapy, hormone manipulation)
• Radiation therapy (external beam, brachytherapy, stereotactic)
• Locoregional interventions (ablation, embolisation, intra-arterial chemotherapy)
• Combined modality and multimodal strategies delivered via a multidisciplinary team (MDT)

Pathophysiology and Oncological Principles

The Rationale for Staging

Staging defines the anatomical extent of disease and drives treatment selection. Most solid tumours use the TNM system:

Stage groupings (I-IV) translate TNM categories into prognostic cohorts and guide whether intent is curative or palliative.

Key Oncological Concepts

• R-status: $R_0$ = clear margins; $R_1$ = microscopic residual; $R_2$ = macroscopic residual. $R_0$ resection is the primary surgical goal in curative intent.
• Tumour biology vs. anatomy: Two tumours with identical TNM staging may behave very differently based on histological subtype, grade, receptor status (e.g., ER/PR/HER2 in breast cancer), and molecular markers (e.g., KRAS, BRAF, mismatch-repair status in colorectal cancer).
• Neoadjuvant vs. adjuvant sequencing: Treatment given before surgery (neoadjuvant) aims to downstage disease, sterilise margins, eliminate micrometastases early, and assess in-vivo chemosensitivity. Treatment after surgery (adjuvant) targets occult residual disease.

Surgical Treatment

Curative Resection

Indications: - Localised or locoregionally advanced disease amenable to $R_0$ resection - Adequate physiological reserve (functional status, cardiorespiratory, hepatic, renal) - No distant metastatic disease except in defined oligometastatic scenarios (see below)

Contraindications (absolute): - Unresectable distant metastatic disease (outside oligometastatic protocols) - Patient unfit for anaesthesia / surgery - Disease encasing major unresectable vascular structures (e.g., superior mesenteric artery involvement in pancreatic head cancer)

Contraindications (relative): - Malnutrition ($< 80\%$ ideal body weight or albumin $< 30\,\text{g/L}$) - consider prehabilitation - High-risk anatomy (portal hypertension, hostile abdomen from prior surgery/radiation) - Borderline resectable disease - consider neoadjuvant downsizing first

Oncological Principles During Resection

• En-bloc resection of tumour and its lymphatic basin
• Adequate proximal and distal margins (e.g., $\geq 5\,\text{cm}$ for colon cancer, no tumour at inked margin for breast lumpectomy, $2\,\text{mm}$ for DCIS)
• Avoidance of tumour fracture / spillage (especially renal, splenic tumours)
• Ligating vascular pedicle early ("no-touch" technique in colorectal surgery)

Sentinel Lymph Node Biopsy (SLNB)

• Established in melanoma and breast cancer
• Avoids full lymph node dissection when the sentinel node is negative, reducing morbidity (lymphoedema, seroma, nerve injury)
• Contraindication: prior regional surgery or radiation disrupting lymphatic channels

Cytoreductive Surgery (CRS) and HIPEC

• Indicated for selected peritoneal surface malignancies: pseudomyxoma peritonei, colorectal peritoneal metastases, peritoneal mesothelioma
• Completeness of cytoreduction (CC-0 or CC-1) is the dominant prognostic variable
• Contraindications: extensive small bowel involvement precluding adequate cytoreduction, poor performance status (ECOG $\geq 3$), unresectable extraperitoneal disease

Palliative Surgery

• Aims to relieve symptoms (obstruction, bleeding, pain, fistula), not cure
• Must be proportionate - operative morbidity/mortality must not outweigh benefit
• Alternatives: endoscopic stenting, percutaneous drainage, venting gastrostomy

Systemic Therapy

Cytotoxic Chemotherapy

General contraindications to chemotherapy: - ECOG performance status $\geq 3$ (unless reversible cause, e.g., bowel obstruction) - Severe organ dysfunction: creatinine clearance $< 30\,\text{mL/min}$ (renally cleared agents), bilirubin $> 3 \times$ upper limit of normal (hepatically metabolised agents) - Active uncontrolled infection - Pregnancy (teratogenicity - particularly first trimester; taxanes and alkylators are especially hazardous) - Severely immunocompromised state

Targeted Biological Agents

Bevacizumab and surgery: impaired angiogenesis leads to anastomotic dehiscence, poor wound healing, and arterial thromboembolism. Standard practice is to withhold for $\geq 4$-$6$ weeks before and after surgery.

Immunotherapy (Checkpoint Inhibitors)

• Mechanism: blockade of PD-1/PD-L1 or CTLA-4, restoring T-cell anti-tumour activity
• Examples: pembrolizumab, nivolumab (PD-1), atezolizumab (PD-L1), ipilimumab (CTLA-4)
• Indications in general surgery oncology:
• Mismatch repair deficient (dMMR) / microsatellite instability-high (MSI-H) colorectal cancer - pembrolizumab now first-line in metastatic dMMR CRC
• Neoadjuvant immunotherapy in oesophagogastric and hepatocellular carcinoma (HCC)
• Melanoma (adjuvant after resection of stage III disease)

Contraindications / cautions: - Active autoimmune disease (relative - risk of exacerbation) - Organ transplant recipients (risk of allograft rejection) - Severe prior immune-related adverse events (irAE) on prior checkpoint inhibitor therapy

Immune-related adverse events (irAE) relevant to the surgeon: - Colitis (risk of perforation - monitor for peritonism) - Hepatitis (check LFTs; may mimic biliary pathology) - Pneumonitis (differentiate from pulmonary metastases) - Endocrinopathies (adrenal insufficiency - steroid cover perioperatively)

Endocrine / Hormone Therapy

• Breast cancer (HR+): tamoxifen (pre-menopausal), aromatase inhibitors - letrozole, anastrozole (post-menopausal)
• Tamoxifen and surgery: increases VTE risk; withhold for $\geq 3$-$5$ days before major surgery; restart once fully ambulant
• Prostate cancer: androgen deprivation therapy (ADT) - relevant when prostate cancer metastasises to bone and becomes a surgical problem (pathological fracture, cord compression)

Radiation Therapy

Modalities

Radiation in Rectal Cancer

• Long course: $45$-$50.4\,\text{Gy}$ in $25$-$28$ fractions with concurrent 5-FU/capecitabine; resection $6$-$8$ weeks later
• Short course: $25\,\text{Gy}$ in 5 fractions; surgery within 1 week or delayed 8-12 weeks (Stockholm III protocol - allows tumour downsizing)
• Indications: T3/T4 or node-positive mid/low rectal cancer; threatened circumferential resection margin (CRM) on MRI
• Contraindications: prior pelvic radiation (cumulative dose limits); inflammatory bowel disease (increased radiation toxicity); pregnancy

Radiation in Oesophagogastric Cancer

• Concurrent chemoradiation (carboplatin/paclitaxel + $41.4\,\text{Gy}$) - the CROSS regimen - is standard neoadjuvant therapy for resectable oesophageal/GOJ adenocarcinoma and SCC

Radiation Complications Relevant to Surgery

• Acute: mucositis, dermatitis, proctitis, diarrhoea, neutropenia
• Late/chronic: radiation enteritis (obstruction, fistula, perforation risk), fibrosis, impaired wound healing, lymphoedema, secondary malignancy
• Surgical implication: irradiated tissue has poor healing; interpose well-vascularised tissue (omentum, muscle flap) when anastomosing in a previously irradiated field

Locoregional and Ablative Therapies

Liver-Directed Therapies

Ablation contraindications: - Tumour abutting major bile duct (risk of biliary stricture) - Tumour $> 5\,\text{cm}$ (inadequate ablation zone) - Uncorrectable coagulopathy - Active biliary obstruction / cholangitis

Multidisciplinary Team (MDT) Decision-Making

Structure and Function

A functioning MDT includes at minimum: - Surgeon (general/subspecialty) - Medical oncologist - Radiation oncologist - Radiologist - Pathologist - Specialist nurse coordinator

Additional members by tumour site: gastroenterologist, hepatologist, dietitian, speech therapist (HN), genetic counsellor.

MDT Decision Framework

1. Confirm diagnosis and staging - histopathological confirmation mandatory before treatment
2. Assess performance status - ECOG score and comorbidities
3. Define treatment intent - curative vs. palliative
4. Sequence modalities - neoadjuvant, surgery, adjuvant
5. Genetic / molecular profiling - MSI, KRAS/NRAS/BRAF, HER2, BRCA
6. Patient values and goals - informed consent, fertility preservation, quality of life

Indications for Neoadjuvant Therapy

Complications and Special Considerations

Oligometastatic Disease

• Defined as $\leq 3$-$5$ metastatic sites, often limited to one organ
• Curative-intent resection of synchronous/metachronous colorectal liver metastases is well-established - $20$-40% five-year survival
• Resectability criteria: adequate future liver remnant (≥20% in normal liver, ≥30% post-chemotherapy, ≥40% with cirrhosis), $R_0$ achievable, no unresectable extrahepatic disease
• Portal vein embolisation (PVE) to hypertrophy contralateral lobe before major hepatectomy when future liver remnant is marginal

Genetic and Hereditary Syndromes

• Lynch syndrome (MLH1, MSH2, MSH6, PMS2): surveillance colonoscopy; consider prophylactic hysterectomy/oophorectomy in women; impacts chemotherapy selection (dMMR tumours respond poorly to 5-FU monotherapy but well to immunotherapy)
• BRCA1/2: bilateral risk-reducing mastectomy, salpingo-oophorectomy; germline testing influences use of PARP inhibitors and platinum chemotherapy
• FAP/AFAP: proctocolectomy timing and extent; duodenal surveillance

Treatment-Related Surgical Complications

• Anastomotic leak: risk elevated after neoadjuvant chemoradiation (especially anterior resection), malnutrition, steroid use, immunotherapy. Leak rate in low anterior resection approximately $10$-15% - defunctioning ileostomy reduces clinical consequences
• Wound healing: impaired by bevacizumab, steroids, malnutrition, prior radiation. Optimise albumin, withhold antiangiogenic agents perioperatively
• Myelosuppression: chemotherapy-induced neutropenia increases perioperative infection risk; check full blood count before elective oncological surgery; delay if neutrophils $< 1.0 \times 10^9/\text{L}$

Perioperative Management in the Oncological Patient

Preoperative Optimisation

• Nutritional assessment: albumin, weight loss $> 10\%$ over 6 months signals high risk; enteral nutrition preferred; parenteral if gut non-functional
• Prehabilitation: structured exercise, smoking cessation, alcohol reduction in the 4-8 weeks before major resection
• Anaemia: iron deficiency anaemia should be treated with IV iron preoperatively; avoid allogenic transfusion where possible (immunosuppressive, infection risk)
• Cardiac and respiratory assessment: METs $\geq 4$ or formal CPET (anaerobic threshold, $\dot{V}O_2\,\text{max}$) for high-risk resections
• DVT prophylaxis: oncological patients carry significantly elevated VTE risk (Caprini/Khorana score); LMWH extended to 28 days post-major abdominal oncological surgery (NICE NG89 / ASCO guidelines)

Perioperative Pharmacology

• Dexamethasone: $8$-$10\,\text{mg}$ IV intraoperatively (PONV prophylaxis, anti-inflammatory); does not impair anastomotic healing at single doses
• NSAIDs: part of multimodal opioid-sparing analgesia in ERAS protocols; use cautiously with bevacizumab (renal toxicity) and in myelosuppressed patients
• Adrenal insufficiency: patients on long-term steroids or after checkpoint inhibitor-related adrenal damage need perioperative steroid supplementation

ERAS in Oncological Surgery

• Early oral feeding, opioid-sparing analgesia, goal-directed fluid therapy, early mobilisation reduce complications and may shorten time to adjuvant chemotherapy
• Delay to adjuvant chemotherapy $> 8$ weeks post-surgery is associated with worse survival in colorectal and breast cancer

Key Exam Points

• Always define treatment intent first (curative vs. palliative) - this drives all subsequent decisions
• $R_0$ resection is the primary surgical goal; margin adequacy is tumour-site specific
• Neoadjuvant therapy is indicated when it improves resectability, pathological response, or survival - know the major regimens by tumour type
• Bevacizumab: withhold $\geq 4$-$6$ weeks perioperatively
• dMMR/MSI-H tumours: resistant to 5-FU monotherapy; exquisitely sensitive to checkpoint inhibitors
• MDT discussion is mandatory before committing to any oncological treatment plan
• Extended VTE prophylaxis (28 days LMWH) after major abdominal cancer surgery
• Immunotherapy irAE colitis can perforate - keep in mind in any checkpoint inhibitor patient presenting with abdominal pain