Most common colorectal cancer type?
How common in CR cancer and who is affected?
4th most common cancer: 2nd most common cause of UK deaths. Mainly affects adult >60. M:F equally affected. M
Originates from the epithelial cells in the colon or rectum.
Most colorectal cancers develop via a progression of normal mucosa to colonic mucosa to invasive adenocarcinoma- this is the adenoma-carcinoma sequence
Spread of CRC
Risk factors for CRC?
Spread occurs via lymphatic, blood (liver, lung, bone) or transcoelomic
IBD (Crohn’s or UC)
Genetic predisposition e.g. FAP and HNPCC (Dominant condition which gives you a higher risk of colon and other cancers)
Peutz-jeghers syndrome: Pigmented spots on lips and buccal mucosa. Small intestinal polyps may bleed obstruct or cause intussusception
- Main predisposing genes are:
- Adenomatous polyposis colic (APC): A tumour suppressor gene, mutation of the APC gene results in growth of adenomatous tissue- this is associated with FAP (familial adenomatous polyposis)
- HNPCC: A DNA mismatch repair gene, mutation to HNPCC leads to effects in DNA repair- associated with Lynch syndrome
Diet: Low fibre or high consumption of red and processed meats
Polyps are removed to prevent later development to cancer
Where are most tumours located in CRC?
Symptoms/ red flags
Left side of the colon
Alteration in bowel habit Colicky abdo pain Rectal bleeding/ Melaena Change in bowel habit Vague abdominal pain Mucous PR Anorexia/Weight loss Abdo or rectal mass
Signs of CRC?
Abdominal mass Perforation Haemorrhage Fistula Anaemia: systemic sign of cancer Left side: Bleeding/mucus PR, altered bowel habit, obstruction, tenesmus, mass PR Right side: Decreased weight
Investigations for CRC?
FBC: To assess for macrocytic anaemia (unusually large red blood cells)
Colonoscopy: Gold standard: suspicious lesions are biopsied/ tattooed for surgery
Sigmoidoscopy: Endoscopy of the rectum and sigmoid colon only
CT colonography: bowel prepped with contrast but less detailed and can’t take biopsy
If family history of FAP refer for DNA test once >15
Carcinogenic Antigen: CEA: should not be used for diagnosis but should be used to monitor progression
CT CAP/TAP, will show evidence of metastasis or mass if present
MRI rectum: definitive imaging test for rectal cancer, will demonstrate soft tissue more appropriately. Will show vascular invasion n(V1-V5), enlarged lymph node or tumour extension out of the bowel wall
Test for RAS and BRAF V600E mutations in all people with metastatic colorectal cancer suitable for systemic anti-cancer treatment
Medical treatment for CRC?
- Mostly used in palliation for colonic cancer
- Consider pre-op SACT (neo-adjuvant) for people with CT4
- Stage III: CAPOX regimen FOR 3 months (capecitabine +oxaliplatin) or if not suitable, Folfox regimen: Fluorouracil, folinic acid and oxaliplatin. If not suitable
- Single agent fluoropyrimidine for 6 months
- Bevacizumab (Anti-VEGF antibody) improves survival when added to combination therapy
- Cetuximab and Panitumumab- anti-EGFR agents improve survival in Kras wild type metastatic colorectal cancer
Surgical options for CRC?
- Right hemicolectomy for caecal ascending or proximal transverse tumours
- Left hemicolectomy for tumours in distal transverse or descending colon
- Sigmoid colectomy for sigmoid tumours
- Abdomino-perineal resection for tumours low in the rectum: removes anus and rectum: sutures over the anus leaving a permanent colostomy
- Endoscopic stenting: should be considered for palliation in malignant obstruction
- Harman’s surgery: complete resection of the recto-sigmoid colon with the formation of an end colostomy and the closure of the rectal stamp. Emergency procedure often used for acute obstruction of a tumour/ significant diverticular disease
What staging system is used for CRC? What are the stages?
Complications of surgical treatment for CRC?
- Dukes A: Limited to muscularis mucosae
- Dukes B: Extension through muscular mucosae
- Dukes C: Involvement of regional lymph nodes
- Dukes D: Distant metastasis
- Bleeding, infection and pain
- Damage to nerves, bladder, ureter or bowel
- Post-operative ileus
- Anaesthetic risks
- Leakage or failure of procedure
What’s the 2ww criteria for colorectal Ca?
For referral: Nice recommends:
- > 40 years with unexplained weight loss and abdo pain
- > 50 years with unexplained rectal bleeding
- > 60 years with iron deficiency anaemia or change in bowel habit
- Positive occult blood test screening
- Age <50 w/ rectal bleeding and 1 of: abdo pain, bowel change, weight loss and irondef anaemia
- Sole IDA without any other explanation is an indication for a 2 week wait referral for colonoscopy and gastroscopy
Occult blood screening-
- Age >50 with unexplained abdo pain or weight loss
- Age <60 with bowel change or Fe def anaemia
What’s the follow up for patients who have had CRC?
For local recurrence and distant metastasis for the first 3 years- follow up should include serum carcinoembryonic antigen (CEA) and CT chest abdo pelvis for the first 3 years
Monitor for lower anterior resection syndrome to people who will potentially have sphincter preserving surgery; symptoms include: increased frequency of stool, urgency with or without incontinence, incomplete emptying, fragmentation of stool and difficulty in differentiating between gas and stool
What test should be conducted prior to starting patients on 5FU?
DPD testing: dihydropyrimidine dehydrogenase
All patients receiving 5FU chemotherapy tested for DPD enzyme deficiency- heterozygous: this results in an inability to metabolise 5FU: severe toxicity and patients have a severe reaction
How common is prostate cancer and who is mainly affected?
80% men >80 years old
Lifetime incidence of 1 in 8 men
Affects black men at the highest incidence
Pathophysiology of prostate cancer:
Genes responsible, pattern of spread, location of most prostate cancers?
What type of cancer is prostate cancer?
Genes include BRCA1 and BRCA2, mismatch repair and HOXB13
Spread may be local (seminal vesicles, bladder and rectum), lymph or haematogenously- sclerotic bony lesions
Most adenocarcinomas arise in the peripheral prostate (95%)
It’s an Androgen dependent cancer
RFs for prostate cancer?
Increasing age (esp >50)
Black ethnicity (afro-caribbean) = 1 in 4 lifetime incidence
Positive FamHx: 1st degree, increases risk by 2.5 times
FamHx of other heritable cancers e.g. breast/ colorectal
High levels of dietary fat
BPH, BRCA2, PTEN gene: tumour suppressor gene
Prostate Ca symptoms ?
Nocturia Terminal Dribbling Haematuria Hesitancy Obstruction Poor Stream Frequency Haematospermia Lower back pain/ bone pain: due to mets
Signs o/E of prostate cancer?
Decreased weight and bone pain
DRE; may show hard irregular prostate
Note that a DRE will only detect tumour on the posterior and lateral aspects of the prostate as these are the only palpable regions
Investigations for prostate Cancer?
DRE + PSA= 2 week referral for men aged 50-69 yo with PSA >3ng/ml and for men aged 70+ with a PSA >5ng/ml. PSA has a high rate of false positives (75%) and false negatives (15%). Normal between 1.0 and 1.5ng/ml
FBC: For anaemia and as a baseline prior to androgen deprivation therapy
U&Es cancer may be obstructing ureters leading to hydronephrosis and kidney dyfunction. Baseline renal function
LFTs: Baseline test for patients who will have androgen deprivation therapy due to risk of hepatitis
Transrectal US and biopsy: TRUS not reliable enough on its own to exclude prostate cancer. For biopsy 10-12 cores removed from US. US probe inserted through the rectum.
Transperineal biopsy= allows better access to the anterior part of the prostate and gives a lower risk of infection: Under LA, needle is inserted through the perineum
Prostate biopsy is conducted if MRI likert >3
DEXA Bone scan to look for mets
Radionuclide scan: for mets: IV injection of isotope, wait 2-3 hours for bone to take up isotope, gamma camera used to take pictures of skeleton
CT/MRI staging: May show enlarged prostate and or enlarged pelvic lymph nodes
Multiparametric MRI: Should be first line investigation for people with suspected clinically localised prostate cancer. Results reported on a likert scale: 1= low suspicion 5= definite cancer
Conservative treatment for prostate cancer?
Surgical options for prostate cancer?
Active surveillance esp if >70 and low risk
Androgen deprivation therapy through bilateral orchidectomy
Radical prostatectomy if <70: disease free survival: indicated for those with localised advanced cancer
Medical management methods for prostate cancer? (There are 6)
Radiotherapy for bone mets or spinal cord compression- intermediate and high risk
- External beam radiotherapy (EBRT): radiation beams are targeted to cancer cells in the prostate. Long term SE= erectile dysfunction and urinary problems
- Brachytherapy= permanent implantation of small balls of radioactive material into the prostate gland- radiation is constantly provided to shrink tumour cells. SE= erectile dysfunction or inflammation to local organs: proctitis or cystitis
- Hormone therapy: GNRH antagonists competitively bind GNRH receptors in the anterior pituitary which results in decreased testosterone. Results in shrinkage of the prostate: Examples are Goserelin or leuprorelin. SEs: hot flushes, erectile dysfunction, gynaecomastia, fatigue and osteoporosis- given as a depot injection into the tummy
- Androgen receptor antagonists: Bicalutamide: this medication blocks cancerous androgen receptors= decreased androgen-driven malignant growth
- Chemotherapy is only indicated in patients with metastatic prostate cancer: drug e.gs include: docetaxel and cabazitaxel- used with prednisolone and recommended for relapsed cancer which has progressed after docetaxel chemotherapy
- High intensive focused ultrasound: used to heat the prostate gland and destroy the tissue
What grading system is used for prostate cancer? Scoring method?
Now, split the management according to risk type pls
Gleeson’s grading system. Score = 2 numbers added together for total score. 1st= grade of most prevalent pattern.2nd = grade of 2nd most prevalent pattern
Low risk disease (6 or below): Active surveillance
Intermediate + high risk (7)
Radical prostatectomy or radical radiotherapy and consider active surveillance for people who choose not to have immediate radical treatment.
Offer androgen deprivation therapy before during or after radical external beam radiotherapy for 6 months
Metastatic/ high risk disease: Hormone relapsed disease: chemotherapy agents (DOCETAXEL- start within 12 weeks and use 6 3 weekly cycles at a dose of 75mg/m2. IV infusion that takes an hour) and anti-hormonal agents
Alternative: External beam radiotherapy: offer hypofractionated radiotherapy or conventional radiotherapy if they cannot tolerate this
Differentiate between watchful waiting and active surveillance?
Watchful waiting: Symptom guided approach: definitive therapy is deferred and hormonal therapy is initiated at a time of symptomatic disease. Suitable for older men or men with significant co-morbidities or slow progressing tumours who are likely to die of other causes
Explain the GP 2ww pathway for prostate cancer
Advantages of TRUS/ Transrectal biopsy
What should you discuss with pts when helping them to decide MRI or prostate biopsy ?
GP > 2WW > Urology PSA clinic (history and DRE) > IR, Transrectal/ transpereneal US»_space; MDT
Pt may have a prostate cancer that MRI has missed
a. Rectal discomfort
b. Blood in semen or urine
c. Urine infection with risk of sepsis
d. Acute urinary retention
To decide between MRI or prostate biopsy- discuss their PSA level, DRE findings, any comorbidities e.g. increasing age and black African Caribbean origin and any history of a negative prostate biopsy
Advantages and disadvantages of….
Surgery: Good option for men aged < 70 with no co-morbidity. Risks of long term incontinence and impotence
Radiotherapy: Non-invasive and good option in older or those with co-morbidity. Risks of long term bowel problems
Brachytherapy: Good option in fit men with no comorbidity
Avoid in men with large prostates or significant urinary symptoms
Internal radiation; delivered as a day case or overnight stay. Allows higher doses of radiation and improved cancer control
SE= erectile dysfunction or inflammation to local organs: proctitis or cystitis
a. Hot flushes
b. Sexual function decline and shrinkage in penis and testis
c. Loss of muscle bulk and strength
d. Memory effects and mood disturbance
e. 10% weight gain and higher risk DM
f. Osteoporosis and higher fracture risk
What should you warn patient about wrt prostate cancer treatment?
alteration of sexual experience and loss of sexual function: to manage encourage patients to access specialist erectile dysfunction services.