Health in Wales
NORTH WALES UROLOGY CANCERS
CLINICAL GUIDELINES
NICE Guidelines for Diagnosis and Treatment of Prostate Cancer
In February 2008, the National Institute for Clinical Excellence published the update guidance on diagnosis and treatment for men with prostate cancer. The following is a quick reference guide for the best practice guidance for diagnosing and treating men with prostate cancer.
Key priorities for implementation
➢ Healthcare professionals should adequately inform men with prostate cancer and their partners or carers about the effects of prostate cancer and the treatment options on their sexual function, physical appearance, continence and other aspects of masculinity. Healthcare professionals should support men and their partners or carers in making treatment decisions, taking into account the effects on quality of life as well as survival.
➢ To help men decide whether to have a prostate biopsy, healthcare professionals should discuss with them their prostate specific antigen (PSA) level, digital rectal examination (DRE) findings (including an estimate of prostate size) and comorbidities, together with their risk factors (including increasing age and black African or black Caribbean ethnicity) and any history of a previous negative prostate biopsy. The serum PSA level alone should not automatically lead to a prostate biopsy.
➢ Men with low-risk localised prostate cancer who are considered suitable for radical treatment should first be offered active surveillance.
➢ Men undergoing radical external beam radiotherapy for localised prostate cancer1 should receive a minimum dose of 74 Gy to the prostate at no more than 2 Gy per fraction.
➢ Healthcare professionals should ensure that men and their partners have early and ongoing access to specialist erectile dysfunction services.
➢ Healthcare professionals should ensure that men with troublesome urinary symptoms after treatment have access to specialist continence services for assessment, diagnosis and conservative treatment. This may include coping strategies, along with pelvic floor muscle re-education, bladder retraining and pharmacotherapy.
➢ Healthcare professionals should refer men with intractable stress incontinence to a specialist surgeon for consideration of an artificial urinary sphincter.
➢ Biochemical relapse (a rising PSA) alone should not necessarily prompt an immediate change in treatment.
➢ Hormonal therapy is not routinely recommended for men with prostate cancer who have a biochemical relapse unless they have:
➢ symptomatic local disease progression, or
➢ any proven metastases, or
➢ a PSA doubling time < 3 months.
➢ When men with prostate cancer develop biochemical evidence of hormone-refractory disease, their treatment options should be discussed by the urological cancer multidisciplinary team (MDT) with a view to seeking an oncologist and/or specialist palliative care opinion, as appropriate.
➢ Healthcare professionals should ensure that palliative care is available when needed and is not limited to the end of life. It should not be restricted to being associated with hospice care.
Diagnosing prostate cancer
Before referral to specialist care, men with suspected prostate cancer should have been offered a DRE and PSA test as set out in ‘Referral guidelines for suspected cancer’ (NICE clinical guideline 27).
Biopsy
➢ Provide information, support and allow sufficient time for the man to decide whether to have a biopsy.
➢ Discuss:
➢ the risks and benefits of biopsy
➢ their individual risk factors (including increasing age and black African or black Caribbean ethnicity)
➢ their estimated prostate size, DRE findings and PSA level
➢ any comorbidities
➢ any previous negative biopsy.
➢ Use nomograms to help with decision making and to predict the biopsy results. Explain their reliability and limitations.
➢ Do not biopsy:
➢ on the basis of serum PSA level alone
➢ if suspicion of prostate cancer is high because of PSA level and evidence of bone metastases, unless required as part of a clinical trial.
➢ The decision as to whether a patient should go on for a TRUS biopsy should be made by a trained urologist and the training of other staff should be controlled by them.
➢ An age reference guideline should be used for when deciding if a patient should have a TRUS biopsy. (Appendix A)
Biopsy results and re-biopsy
➢ The urological cancer MDT should review the biopsy results.
➢ After a negative biopsy result the urological cancer MDT should review the man’s risk (life expectancy, PSA level, DRE findings and estimated prostate size) and discuss with him the risks and benefits of a re-biopsy.
Before starting treatment
➢ Discuss all relevant management options.
➢ Inform men that treatment may result in:
➢ altered physical appearance
➢ altered sexual experience
➢ possible loss of sexual function, ejaculation and fertility
➢ Changes in urinary function.
➢ Support men in making treatment decisions, taking into account survival and quality of life benefits. Use a decision aid.2
➢ Advise men about the potential long-term adverse effects of treatment and when and how to report them.
➢ Offer:
➢ sperm storage
➢ ongoing access to erectile dysfunction services
➢ ongoing access to specialist continence services
➢ ongoing access to specialist psychosexual services
➢ a urological assessment if troublesome urinary symptoms are present.
➢ Assign a risk category to men with localised prostate cancer.
➢ To offer Sperm donation to all patients would be mostly inappropriate as many patients who are diagnosed with prostate cancer are elderly. However in some cases it must be considered when reviewing the patient.
Table 1 Risk stratification criteria for men with localised prostate cancer.
Men with clinical stageT3–T4 cancers have locally advanced disease.
[pic]
Imaging
➢ Do not routinely image men for whom no radical treatment is intended.
➢ If men with high-risk localised and locally advanced prostate cancer intend to have radical treatment, offer pelvic magnetic resonance imaging (MRI) or computerised tomography, if MRI is contraindicated.
➢ Perform bone scan if hormonal therapy is being deferred through watchful waiting in asymptomatic men at high risk of bone complications.
➢ Positron emission tomography and magnetic resonance spectroscopy (MRS) are not recommended in routine clinical practice. MRS may be performed as part of a clinical trial.
Localised prostate cancer
[pic]
[pic]
Watchful waiting
➢ If men choose watchful waiting and show evidence of disease progression, they should be reviewed by a member of the urological cancer MDT.
Active surveillance
➢ Active surveillance is the preferred option for low-risk men who are candidates for radical treatment. It is particularly suitable for men with clinical stage T1c, Gleason score 3+3 and PSA density < 0.15 ng/ml/ml who have cancer in less than 50% of their biopsy cores, with < 10 mm of any core involved.
➢ Candidates for active surveillance should:
➢ have had at least 10 biopsy cores taken
➢ have at least one re-biopsy which may be performed according to the ProSTART protocol.3
➢ If men on active surveillance show evidence of disease progression, offer radical treatment. Treatment decisions should be made with the man, taking into account comorbidities and life expectancy.
➢ Offering patients a re-biopsy is not necessary and potentially harmful to the patient.
➢ To review life expectancy tables when discussing patients during MDT meetings.
Radical treatments
➢ All candidates for radical treatment should have the opportunity to discuss their treatment options with a surgical oncologist and a clinical oncologist.
➢ Offer adjuvant hormonal therapy for a minimum of 2 years to men receiving radiotherapy who have a Gleason score of ≥ 8.
Locally advanced prostate cancer
➢ Offer:
- neoadjuvant and concurrent luteinising hormone-releasing hormone agonist (LHRHa) therapy for 3–6 months to men receiving radiotherapy
- adjuvant hormonal therapy for a minimum of 2 years to men receiving radiotherapy who have a Gleason score of ≥ 8.
➢ Consider pelvic radiotherapy for men with > 15% risk of pelvic lymph node involvement who are to receive neoadjuvant hormonal therapy and radiotherapy. Estimate risk using the Roach formula: 2/3 PSA + (10 x [Gleason score – 6]).
➢ Do not offer:
➢ adjuvant hormonal therapy in addition to prostatectomy, even to men with margin-positive disease (unless as part of a clinical trial)
➢ bisphosphonates to prevent bone metastases
➢ immediate post-operative radiotherapy routinely after prostatectomy, even to men with margin-positive disease (unless as part of a clinical trial)
➢ high-intensity focused ultrasound (HIFU) or cryotherapy (unless as part of a clinical trial).
➢ To aim to give specific patients radiotherapy at a minimum dose of 74 Gy.
Metastatic prostate cancer
➢ Offer:
➢ bilateral orchidectomy as an alternative to continuous LHRHa therapy
➢ monotherapy with bicalutamide (150 mg)4 if the man hopes to retain sexual function and is willing to accept gynaecomastia and reduced survival
➢ androgen withdrawal in place of bicalutamide, if bicalutamide is not successful in retaining sexual function. Advise that regular resistance exercise reduces fatigue and improves quality of life.
➢ Consider offering intermittent androgen withdrawal, providing the man is informed about the lack of long-term effectiveness evidence.
➢ Do not offer combined androgen blockade as a first-line treatment.
➢ Combined androgen blockade is felt to be a better form of treatment and that there is evidence to suggest this.
Hormone-refractory prostate cancer
➢ Discuss treatment options with the urological cancer MDT and seek oncology and/or palliative care advice, as appropriate.
➢ Offer:
➢ docetaxel (within its licensed indications) only if Karnofsky score is ≥ 60%. Stop treatment after 10 planned cycles or if severe adverse events occur or if disease progresses (shown by clinical or laboratory criteria or imaging). Do not repeat treatment cycles if disease recurs5
➢ a corticosteroid (for example, dexamethasone 0.5 mg daily) as a third-line therapy after androgenwithdrawal and anti-androgen therapy
➢ spinal MRI if spinal metastases are found and spine-related symptoms develop
➢ decompression of the urinary tract by percutaneous nephrostomy or insertion of a double J stent to men with obstructive uropathy. Discuss the option of no intervention.
➢ Do not offer:
➢ routine spinal MRI to men with known bone metastases
➢ bisphosphonates to prevent or reduce the complications of bone metastases.
➢ The Karnofsky (Appendix B) scoring system is not being used within YGC but ECOG (Appendix C) a similar scoring system is used.
Palliative care
➢ Discuss the man’s preferences for palliative care (and those of his partner and carers) as soon as possible.
➢ Identify the preferred place of care.
➢ Do not limit palliative care to hospice care; integrate into coordinated care and ensure it is available when needed.
Offer:
➢ tailored information and treatment and care plan
➢ access to specialist urology and palliative care teams to discuss changes in disease status or symptoms
➢ a regular assessment of the man’s needs.
Follow-up
➢ Discuss purpose, duration, frequency and location of follow-up with the man and his partner or carers.
➢ Follow up men who choose watchful waiting in primary care and measure their PSA at least annually.
➢ Check PSA levels of men who are having radical treatment:
➢ at least 6 weeks after treatment
➢ at least every 6 months for the first 2 years
➢ at least once a year after the first 2 years.
➢ Do not carry out routine DRE while PSA remains at baseline levels.
➢ After 2 years, offer follow-up outside hospital to men with stable PSA and no treatment
➢ complications (unless clinic-based follow-up is required as part of a clinical trial). Ensure the man has access to the urological cancer MDT.
➢ To review patients in the MDT 6 weeks post op that have had radical surgery.
Managing relapse after radical treatment
➢ Analyse serial PSA using the same assay technique.
➢ Perform biopsy after radiotherapy only in men considered for local salvage therapy as part of a clinical trial.
➢ If biochemical relapse (rising PSA) is identified:
➢ estimate PSA doubling time (using at least 3 measurements over 6 months)
➢ offer radiotherapy of the prostatic bed to men who have had a prostatectomy and have no metastases
➢ consider man for entry into an appropriate clinical trial.6
➢ Perform an isotope bone scan if symptoms or PSA trends suggest metastases and the man is considering salvage therapy.
➢ Do not change treatment based on biochemical relapse alone.
➢ Do not offer:
➢ biopsy of the prostatic bed to men who have had prostatectomy
➢ routine MRI before salvage radiotherapy
➢ hormonal therapy, unless the man has symptomatic disease progression, proven metastases or a PSA doubling time < 3 months.
Managing the side effects of treatment
Radiation-induced damage
➢ Use flexible sigmoidoscopy to investigate symptoms of radiation-induced enteropathy to exclude inflammatory bowel disease or cancer of the large bowel.
➢ Offer flexible sigmoidoscopy every 5 years after radical radiotherapy.
➢ Take care when performing anterior wall rectal biopsy after brachytherapy because of the risk of fistulation.
➢ Do not offer steroid enemas for treating radiation proctopathy.
➢ Radiation-induced injury to the gastrointestinal tract should form part of oncologists’ and gastroenterologists’ training.
Erectile function
➢ Offer phosphodiesterase type 5 (PDE5) inhibitors to men who experience loss of erectile function. If PDE5 inhibitors fail or are contraindicated, offer vacuum devices, intraurethral inserts, penile injections or prostheses.
Urinary symptoms
➢ Refer men with intractable stress incontinence to a specialist surgeon for a possible artificial urinary sphincter.
➢ Do not offer bulking agents to treat stress incontinence.
Side effects of hormonal treatments
➢ Offer oral or parenteral synthetic progestogens for hot flushes. Offer oral therapy for 2 weeks and re-start when flushes recur, if effective.
➢ Offer prophylactic orthovoltage or electron beam radiotherapy to breast buds (single 8 Gy fraction) within the first month of long-term (> 6 months) treatment with bicalutamide monotherapy.
➢ Consider weekly tamoxifen if radiotherapy does not prevent gynaecomastia.
➢ Do not routinely offer bisphosphonates to prevent osteoporosis in men receiving androgen withdrawal therapy.
Pain
➢ Consider strontium-89 for painful bone metastases in men with hormone-refractory prostate cancer, especially if they are unlikely to receive myelosuppressive chemotherapy.
➢ Consider bisphosphonates for pain relief in men with hormone-refractory prostate cancer when analgesics and radiotherapy have failed. Choose intravenous or oral dosing according to convenience, tolerability and cost.
| | |
|AGE |PSA |
| | |
|40 - 49 |0 - 2.5 |
|50 - 59 |0 - 3.5 |
|60 - 69 |0 - 4.5 |
|70 - 79 |0 - 6.5 |
|Reference |
|Age-specific Reference Ranges for Serum PSA, Oesterling J.E. |
|BJUI.Vol 85, Page 1-78, June 2000, H Toussi, C Williams, M Giles, V Srinivasan, C M Evans. |
|100 % |normal, no complaints, no signs of disease |
|90% |capable of normal activity, few symptoms or signs of disease |
|80% |normal activity with some difficulty, some symptoms or signs |
|70% |caring for self, not capable of normal activity or work |
|60% |requiring some help, can take care of most personal requirements |
|50% |requires help often, requires frequent medical care |
|40% |disabled, requires special care and help |
|30% |severely disabled, hospital admission indicated but no risk of death |
|20% |very ill, urgently requiring admission, requires supportive measures or treatment |
|10% |moribund, rapidly progressive fatal disease processes |
|0% |death |
ECOG
Eastern Conference Oncology Group
Zubrod Score – used by WHO in trials
(Appendix C)
|0 |Asymptomatic |
|1 |Symptomatic completely ambulant |
|2 |Symptomatic, 50% of time in bed but not bed bound |
|4 |Bed bound |
|5 |Death |
Renal Cancer Protocol
Renal cell carcinoma is the most frequently occurring solid lesion within the kidney and compromised different renal cell carcinoma types with specific histopathological and genetic characteristics. Aetiological factors include lifestyle factors such as smoking, obesity and anti-hypertensive therapy. Cost effective prophylaxis is to avoid cigarette smoking and obesity.
Increasing numbers of incidentally diagnosed renal cell carcinomas are being found as a result of ultrasound and CT. Tumours are often smaller and of lower stage but despite the increased incidental detection rate the mortality from renal cell carcinoma has remained unaffected and parallel to the incidence.
Diagnosis and Staging
More than 50% of renal cell carcinomas are detected incidentally using non-invasive imaging for the evaluation of a variety of non-specific symptom complexes. The classic traid of flank pain, gross haematuria and palpable abdominal mass in now rarely found (6-10%). Para-neoplastic syndromes are found in up to 30% of patients with symptomatic renal cell carcinoma. The most common of these are hypertension, cachexia, weight loss, pyrexia, neuromyopathy and myeloidosis, elevated erythrocyte sedimentation rate, anaemia, abnormal liver function, hypercalcaemia and polycythaemia. Around 25-30% of patients are diagnosed due to symptoms associated with metastatic disease.
Physical examinations has limited role in diagnosis by may be valuable in cases of palpable abdominal mass, palpable cervical lymphadenopathy, a non-reducing varicoele or bilateral lower extremity oedema which suggests venous involvement.
The most commonly assess laboratory parameter are heamoglonin, erythrocyte sedimentation rate, alkaline phospatase and serum calcium.
Radiological Investigations
The majority of renal tumours are diagnosed by ultrasound initially. The detection of a solid mass on ultrasound should be further investiagted with a high quality CT scan using contrast medium to verify the diagnosis, provide information on the controlateral kidney and to stage the tumour. Chest CT should be used for chest staging. Magnetic resonance imaging can be reserved primarily for patients with locally advanced malignancy, possibly venous involvement, renal insufficiency or allergy to intravenous contrast. Magnetic resonance imaging is an option for the evaluation of inferior vena cava thrombus extension and in the evaluation of unclassified renal masses.
Most bone and brain metastases are symptomatic at the time of diagnosis and if indicated by clinical or laboratory signs or symptoms diagnostic procedures such as bone scan, brain CT or MRI may be applied. Routing bone scan and brain CT are not generally indicated. Renal arteriography, inferior vena cavography or fine needle biopsy may be considered in selected cases.
Classification and Prognostic Factors
The 2002 TNM stage classification system is generally recommended for clinical and scientific use.
Anatomical factors influencing prognosis include tumour size, venous invasion, renal captor invasion, adrenal involvement and lymph node staging and distant metastases. These are commonly gathered together in the universally used 2002 TNM staging classification.
Histological factors include Fuhrman grade histological sub-type, presence of sarcomatoid features, microvascular invasion, tumour necrosis and collecting system invasion.
Use of integrated prognostic systems is not routinely recommended but may provide rationale for prognostic prediction useful for including patients in clinical trials.
Treatment of Localised Disease
Surgical therapy is the only curative therapeutic approach for the treatment of renal cell cancer. Provided that pre operative imaging procedures (CT, MRI) reveal negative findings there is no need for adrenalectomy unless tumours are more than 7cm or are large, upper pole tumours associated with a risk of direct invasion of the adrenal gland.
In general extended lymphadenectomy cannot be considered to be the therapeutic standard thought in selected cases of lymph node disease limited to the retroperitoneal space extended lymphadenectomy might improve a patient’s clinical prognosis.
There is no benefit in performing tumour embolisation before routine radical nephrectomy but it may be indicated in patients unfit for surgical intervention or prior to surgical resection of large, paravertebral metastases.
There is no evidence to favour a specific surgical approach for radical nephrectomy.
Nephron sparing surgery may be indicated for absolute, relative or elective reasons. Absolute indications may be an anatomically or functionally solitary kidney. Relative indications may be a functioning opposite kidney affected by a condition that might impair renal functioning opposite kidney affected by a condition that might impair renal function in the future. Electively when unilateral renal cell cancer occurs with a healthy controlateral kidney. Relative indications include patient with hereditary forms of renal cell carcinoma who are at risk of developing tumours in the controlateral kidney in the future.
Nephron sparing surgery for renal cell carcinoma in patients with a solitary tumour less than 4 cm in diameter produces recurrence free and long-term survival rates similar to those observed after radical nephrectomy. If tumours of larger size are treated with nephron sparing surgery follow up should be intensified due to the increase risk of intra renal recurrences.
Laparoscopic radical nephrectomy may now be considered a standard of care for patients with T1-2 renal carcinomas. Laparoscopic tumour nephrectomy should be promoted in centres treating kidney tumours.
Partial laparoscopic nephrectomy may be used for the treatment of relatively small peripheral renal tumours. Large studies revealing reliable long-term equivalents to open surgery are not available at present. They may be increased post operative complications.
Open partial nephrectomy currently remains the standard of care but laparoscopic partial nephrectomy might be performed at experienced centres.
Alternative Minimally Invasive Treatments
Include percutaneous radio frequency ablation, cyro ablation, microwave ablation, laser ablation and high intensity focussed ultrasound ablation. All have the current state of experimental options for kidney cancer and should be further evaluated in clinical trials. Patients unsuitable for open or laparoscopic surgery should be considered for above mentioned treatments.
Outside controlled clinical trials there is no indication for adjuvant therapy following surgery.
Metastatic Disease
Tumour nephrectomy is recommended for metastatic renal cell carcinoma patients with good performance status when combined with Interferon Alpha.
Complete removal of metastatic lesions contributes to an improvement in clinical prognosis. When there has been complete resection of metastatic lesions or isolated local recurrences immunotherapy does not contribute to an improvement in the clinical prognosis.
In patients with synchronous metastatic spread metastasectomy should be performed if performance status is good and the disease is respectable. Metastastectomy should be performed in patients with residual and respectable metastatic lesions previously responding to immunotherapy and/or limited (solitary lesion) number of metachranous metastases in order to improve the patient’s prognosis.
In individual cases radiotherapy for the treatment of brain metastases and osseus lesions can induce relief from symptoms due to metastatic renal cell carcinoma.
Systemic Therapy for Metastatic Renal Cell Cancer
Chemotherapy as monotherapy should not be considered effective in patients with metastatic renal cell caner.
Interferon Alpha can be considered as a control arm for studies investigating the efficacy of new drugs. Only selected patients with metastatic renal cell cancer with a good risk profile and clear cell sub-type histology derived clinical benefit from immunotherapy with interleukin 2 or Interferon Alpha.
Tyrosinkinase inhibitors should be considered as first or second line treatment for metastatic renal cell cancer patients (not currently available on the NHS in Wales). Sorafenib is advised as a second line treatment for metastatic renal cell cancer (not currently available to NHS patients in Wales).
Sunitinib is advised as first line therapy in good and intermediate risk patients (not currently available to NHS patients in Wales). Adjuvant therapy will change over the course of time
Surveillance Following Radical Surgery for Renal Cell Carcinoma
Surveillance after radical surgery allows the clinician to monitor or identify post operative complications, renal function, local recurrence, recurrence in the controlateral kidney and the development of metastases.
It is reasonable to modify follow up taking into account the risk of developing recurrence of metastases.
When the likelihood of relapse is low follow by chest x-ray and abdominal ultrasound are appropriate. Where the risk is intermediate or high CT of chest and abdomen is the investigation of choice thought the morbidity of radiation dose with repeated CT should be taken into account. Though it may be argued that follow up by imaging is not cost affective after 5 years there is no consensus on the period of surveillance. Intensity and length of the follow up programme should, therefore, be adapted to the individual patient.
Follow up for Radical Nephrectomy
|STAGE |VISIT |EXAMINATION |OPTIONAL |PURPOSE |
| | |Physical exam |Alk Phos |Exclude complication |
|All T | | | |of surgery |
| | |Creatinine | |Establish remaining kidney function |
| | | | | |
| | |Hb | |To check recovery of periop blood loss |
|STAGE |VISIT |EXAMINATION |OPTIONAL |PURPOSE |
| |Every 6 months for 3 |Physical exam Chest X-ray |Alk Phos |Exclude complication of surgery and LR and LN |
|T1, T2 |years | | |metastases |
| | | |Kidney imaging |Exclude pulmonary metastasis and LR after partial |
| |Every year for 3-5 | |(familial, papillary or|nephrectomy |
| |years | |VHL) | |
|STAGE |VISIT |EXAMINATION |OPTIONAL |PURPOSE |
| |Every 6 months for 3 |Physical exam | |Exclude complication of surgery and LR AND LN |
|T3, T4 |years | | |Metastasis |
| | |Chest X-ray | |Exclude pulmonary metastasis and LR after partial |
| | | | |nephrectomy |
| | |Retroperitoneal imaging | | |
| |Every year from 3-10 | | |To detect LR, contralateral metastases or |
| |years | | |neo-ocurrence |
➢ Alk Phos: If elevated preoperatively needs follow-up
➢ ? Bone or liver mets.
➢ Imaging of retroperitoneum by abdominal US or CT is recommended
➢ only after NSS or locally advanced disease, e.g.T3,T4
➢ There is a small but continuous risk of recurrence or metastasis from 5-15yrs
Follow up for NSS
|A11 T |4-6/52 |UEC, IVU, US, Hb |CT |
| | | | |
|T1 |Hb blood yearly |CXR yearly | |
| | | | |
|T2 |Hb yearly |CXR yearly |CT 2 yearly |
| | | | |
|T3 |Hb and blood yearly |CXR yearly |CT 6/12 X 2 years |
| | | |2 yearly thereafter |
Treatment Protocol for TCC Bladder
➢ Non muscle invasive bladder tumour
➢ Muscle invasive and metastatic bladder tumour
For treatment purpose TCC bladder is classified as non muscle invasive and muscle invasive tumour. Approximately 70% of patients with bladder cancer present with disease confined to the mucosa. 30% present with muscle-invasive or metastatic tumour. Only a third of the patients who are initially diagnosed with a superficial TCC will develop an invasive tumour during follow-up
The reason for clubbing invasive and metastatic tumour in to one group is because if TCC crosses the lamina propria, they are prone for metastasis and studies quote the incidence of micrometastasis is around 40%
TNM Classification
[pic]
WHO grading 1973 – 2004
1973
Grade 0: Urothelial papilloma
Grade 1: well differentiated
Grade 2: moderately differentiated
Grade 3: poorly differentiated
2004
1. Urothelial papilloma
2. Papillary urothelial neoplasm of low malignant potential (PUNLMP)
3. Low-grade papillary urothelial carcinoma
4. High-grade papillary urothelial carcinoma
Non muscle invasive bladder tumour
Assessment of Ta/T1 TCC
➢ Urine analysis & Urine cytology
➢ Renal and bladder ultrasonography and/or IVU in selected cases (grade 3 tumours)
➢ Flexible Cystoscopy
➢ TUR BT
➢ TUR of underlying muscle tissue
➢ Selected biopsies of abnormal-looking urothelium
➢ Random bladder biopsy
Adjuvant treatment
One immediate post op instillation
- decreases the relative risk of recurrence by 40% in Ta/T1 tumours
|Intra vesical therapy |Recurrence |Progression |
|Mitomycin/ Epirubicin |Reduced |No change |
|BCG |Reduced |Reduced |
|Intra vesical therapy |Duration |
|Mitomycin/ Epirubicin |Once a week for 6 weeks |
|BCG |Once a week for 6 weeks |
| |Maintenance – once a month for at least a year |
A meta-analysis of seven randomized trials has demonstrated that one immediate instillation of chemotherapy after TUR decreases the relative risk of recurrence by 40%. Immediate instillation should not be given in case of overt or suspected intra- or extra-peritoneal perforation.
The choice between chemotherapy or immunotherapy largely depends on the risk that needs to be reduced: recurrence or progression.
Adjuvant chemotherapy bladder instillations are effective in preventing recurrence in low-grade tumours. In high-grade tumours, bacillus Calmette-Guerin (BCG) therapy has proven to be superior to intravesical chemotherapy.
In the 20 trials in which some form of BCG maintenance was given, a reduction of 37% in the risk of progression was observed
Failure of adjuvant treatment
|Intra vesical therapy |Action |
|Mitomycin/ Epirubicin |Try repeat instillation or BCG |
|BCG |Re instillation or Radical Cystectomy |
Muscle invasive and metastatic bladder tumour
Staging
➢ TUR and bimanual palpation
➢ CT/MRI
➢ Bone scan
Radical Cystectomy
Gold standard
Primary indication - T2-T4a, N0-NX, M0
High risk group
1. Recurring T1 G3
2. BCG resistant Tis
3. Extensive papillary tumor difficult to control with conservative measures
Guidelines Primary Radiotherapy
➢ Radiotherapy is a reasonable treatment option in patients who wish to preserve their bladder
➢ A multidisciplinary approach involving urologist, radiotherapist, medical oncologist and pathologist
➢ Regular follow-up schedule in order to perform salvage cystectomy in patients with recurrent disease as soon as possible
Systemic Chemotherapy
➢ Metastatic disease
➢ Cisplatin-containing combination chemotherapy
➢ MVAC and GC regims.
➢ Complete remissions in 40-70%
➢ Median survival is 12-14 months
➢ A minimal survival benefit with neo-adjuvant chemotherapy before cystectomy or RT
Signed on behalf of Glan Clwyd Hospital, North Wales NHS Trust by
Mr. V Srinivasan, Lead Clinician for the Urology MDT
Signed:
Date:
Signed on behalf of Wrexham Maelor Hospital, North Wales NHS Trust by
Mr Alan De Bolla, Lead Clinician for the Urology MDT
Signed:
Date:
Signed on behalf of the North West Wales NHS trust by Mr. Ernest Ahiaku, Lead Clinician for the Ysbyty Gwynedd Urology MDT
Signed:
Date:
-----------------------
Table 2 Treatment and management options for men with localised prostate cancer. Radical treatments
Age-Specific Reference Ranges for Serum PSA*
(Appendix A)
Karnofsky scoring
(Appendix B)
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