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Wacn prostate cancer guidelines

Prostate Cancer
Date of Endorsement: August 14th 2009 Review Date: September 2010 Authors: Mr. RD Mills & Mr. WH Turner Guidelines for the Management of Prostate Cancer Title: Guidelines for the Management of Prostate Cancer
Mr. RD Mills and Mr WH Turner
Document Owner:
Anglia Cancer Network The Gibson Centre Newmarket Hospital Exning Road Newmarket, Suffolk, CB8 7JG
Status: Final
Endorsement date: August 14th 2009

Review date: September 2010

Guidelines for the Management of Prostate Cancer Guidelines for the Management of Prostate Cancer Introduction

The purpose of this manual is to collate the numerous guidelines that exist, into a
working manual for the management of prostate cancer within the Anglia Cancer
Network. It should act as a summary guide for the management of patients with
prostate cancer based on the available published evidence. Its scope is to aid all
health practitioners involved in the patient from primary care and referral through
treatment to follow up. However, as constant modifications are being made, these
guidelines should only be used to give an indication of current management. They
should not be used to treat patients without checking that changes have not been
These guidelines have been developed by discussion between clinicians within the
Anglia Cancer Network Urology Site Specific Group but without the establishment of
a formal guideline development group. These guidelines have been endorsed by the
Anglia Cancer Network Urology Site Specific Group. They will be reviewed and
updated on an annual basis or more frequently as required.
The guidelines are intended as a working document for daily practice. For more
detailed sources, and for educational material, please refer to guidelines produced
by eg, NICE, BAUS, EAU, AUA.

For referrals from Primary and Secondary Care, see AngCN prostate cancer
Prostate biopsy

The following can be considered as indications for biopsy:
 Any patient with PSA > age adjusted upper limit (ULN)
 Other men with who wish to have a biopsy based on their PSA and general level  Any patient with palpably abnormal prostate.
A minimum of ten samples should be taken to reduce the risk of underestimating
tumour grade.
See AngCN Pathology guidelines for details of pathology assessment of biopsy
LMDT review

All positive prostate biopsies should be discussed in the LMDT.
The need for staging investigations can be based on the prostate cancer risk categories devised by D’Amico. Guidelines for the Management of Prostate Cancer Low Risk –T1c or T2a, Gleason <6 and PSA <10 ug/l
Intermediate Risk – T2b or Gleason 7 or PSA >10 and < 20 ug/l
High Risk - > T2c or Gleason > 8 or PSA > 20 ug/l


 Bone scintigram in all patients in medium and high risk categories, or if bone
 MR pelvis in all patients being considered for radical therapy in medium and high risk categories. MRI should be performed 4 weeks after Standard Biopsy and
6 weeks after MDA or Saturation Biopsy to allow changes due to bleeding
from biopsy to subside.

Defining Tumour Stage and Grade
Pathology and tumour grade

The recommended histological grading system for adenocarcinoma is described by
Gleason (see Appendix 1).
Tumour stage

whereas in the USA Whitmore-Jewett
system is popular.
Management options for early prostate cancer
Patients will have been assigned a D’Amico Risk Category – low, intermediate or
For most patients there are will be a number of options available for the
management of their early stage prostate cancer. These should be discussed with
the patient. All patients with prostate cancer being considered for surgery or
brachytherapy should be discussed with the Specialist Multi-disciplinary Team at
Addenbrooke’s or the Norfolk and Norwich University Hospital, and counselled
locally initially by the urological and oncological core members of their LMDT.
The main management options include:
1. Active Monitoring or active surveillance
2. Radical prostatectomy
3. 3-D conformal external beam radiotherapy - EBRT
4. Radioactive seed implantation - brachytherapy
5. Hormone therapy alone
1. Active Monitoring or Active Surveillance alone

Guidelines for the Management of Prostate Cancer  Older frail patients or those with serious medical conditions  Gleason sum 6 or 7(3+4) (well/moderately well differentiated) tumours The risk of progression is related to grade and stage. These risks should be explained to the patient. If the patient opts for active monitoring and if he is suitable for radical treatment if his disease progresses, he should be followed up initially at three monthly intervals with a PSA and also rectal examination at least every 12 months. At a later stage once stability of the PSA reading has been established, the appointment interval may be increased to 6 monthly. Monitoring should include a measure of PSA doubling time (PDAdt). Active surveillance is similar but involves regular biopsy. As yet there is no randomized evidence of effectiveness and should not be considered standard practice. The patient’s managed may be informed by the PSAdt, some suggestions are put below, but patient choice remains paramount.  PSAdt <10 months – intervention  PSAdt >4 years – no intervention / continued active monitoring  PDAdt between 10 months and 4 years – consider treatment according to patient parameters (i.e. Radical or palliative treatment).
2. Radical Prostatectomy

Usually men undergoing radical prostatectomy would have the following criteria.
 Patients with a predicted life expectancy in excess of 10-15 years; usually  Some men with operable cT3 disease may wish surgery  Patient understands and accepts the risk of impotence and/or incontinence.  Patient preference.  Prostatectomy may be advantageous if there is a history of marked LUTS.  Patients should be offered open, laparoscopic and robotic radical prostatectomy, depending on patient preference, after appropriate counselling, supplemented by information sheets.
3. External beam radiotherapy - EBRT
Patients should be staged as outlined above.
Guidelines for the Management of Prostate Cancer  No history of radio sensitivity or previous pelvic radiotherapy.  Contraindications to brachytherapy or radical prostatectomy.
Radiotherapy and hormone therapy recommendations:

a) Radical radiotherapy without associated hormone therapy

 pT1a/pT1c (10% sample volume) and Gleason <7 and PSA in normal range

b) Hormone cyto-reduction 3-6 months before and concurrent with radical

 pT1b/c-clinical

c) Continuing hormones after radical radiotherapy (3 years)
Patients at a higher risk of systemic disease may be considered for adjuvant
hormone therapy for 3 years.
 Initial PSA > 30 ug/l (not in acute retention or with UTI)
In this setting 3 monthly LHRHa depot injections are preferred.

d) Indefinite Hormone Therapy Followed By Palliative Radiotherapy

 N+ and/or M+ disease

In this setting 3 monthly LHRHa depot injections are preferred.
Patients intending to pursue long term ADT should be considered for bone
densitometry at the start of their treatment and then at 2 yearly intervals. If bone
density is < -2 or worse SD below the mean expected value, the patient should
receive oral bisphosphonates and calcium supplements as per the advice of the
bone dens.
Salvage prostatic cryotherapy

In the event of biochemical recurrence after EBRT, the SMDT may referral to the
Norfolk and Norwich University Hospital for consideration of salvage cryotherapy to
the prostate.
Guidelines for the Management of Prostate Cancer 4. Radioactive seed implantation – Brachytherapy

Patients may be considered with the following factors:-
 Well or moderately differentiated tumours (Gleason < 7).  No greater than 2 positive cores and <20% of biopsy material in positive cores  PSA <15 ug/l if Gleason 6 (3+3) and 10 ug/l if Gleason 7(3+4)  Prostate volume 20-50 mls-, no pubic arch interference  Minimal lower urinary tract symptoms (LUTS) - IPSS < 8/35 Patients should be referred to the Oncology Department at Addenbrooke’s Hospital
5. Radiotherapy after radical prostatectomy

Indications include a rising PSA post-operatively, or a PSA which fails to become
unrecordable, in men with pT3a disease, bladder neck or seminal vesicle
involvement, and with broadly positive margins. Positive margins alone are not an
indication for immediate post-operative radiotherapy unless the PSA begins to rise.
The use of androgen deprivation in this setting is decided on an individual patient
basis. Patients should be warned that there is a risk of worsening urinary
incontinence following radiotherapy in this setting.
6. Long term androgen deprivation therapy alone

Patients who may reasonably be considered include:-
 Significant urinary symptoms may increase the advantages of offering  No other significant risk factor for osteoporosis The options for androgen deprivation are:-  Anti-androgen monotherapy therapy e.g. Bicalutamide, may be considered for selected patients in whom active therapy is indicated but potency or the side-effects of LHRH analogues are important issues.
See Appendix 3 for bone densitometry indications.
Management options based on D’Amico classification

Low risk

The following options are possible, assuming a life expectancy of at least 10 years
and fitness for radical surgery, and all should be discussed with the patient:
Guidelines for the Management of Prostate Cancer If co-morbidity suggest that the patient’s life expectancy is less than 10 years, active
treatments may not be appropriate.
Intermediate risk

Active treatment will be preferred to either active monitoring or active surveillance,
although the latter options can be considered. Active treatment will usually be either
radical surgery or EBRT, but some intermediate risk men may meet the indications
for brachytherapy. Active treatment in some men, who are not candidates for radical
treatment on grounds of age or frailty, may be with androgen deprivation therapy
High risk
Active treatment is required. Radical treatment may be considered for men who
otherwise have a life expectancy of at least 10 years: EBRT may be an option, and
for those fit enough, radical surgery may be considered. Brachytherapy is not an
Palliative treatment with androgen deprivation therapy, and possibly also with
palliative radiotherapy, will be appropriate for men not treated radically.
Management options for locally advanced prostate cancer (without

Patients with T3b or T4 could be considered for radical or palliative radiotherapy plus
hormone therapy (see radiotherapy section). Other options include hormone therapy
alone or active monitoring in patients with other serious medical conditions or patient
preference. Radical prostatectomy or brachytherapy are seldom appropriate for
patients with stage cT3b disease or more advanced disease.

See Appendix 3 for bone densitometry indications.
Management Options for Metastatic Disease

Local therapies for the prostate depend on the symptoms, extent of disease (locally and metastatic) and the performance status of the patient. Assessing the symptomatic response to hormone therapy is the usual course but palliative TURP or radiotherapy may well be appropriate (Radical prostatectomy or brachytherapy are not considered). Treatment of systemic disease depends on the existing therapies at the time of metastatic development and the individual circumstances of the patient. An example of a possible pathway, purely for illustrative purposes, is: First line
Second line
Third line
Fourth line
Guidelines for the Management of Prostate Cancer Next Add Antiandrogen

Other Considerations

 Consider breast bud irradiation if long term bicalutamide or diethystilboestrol  Cyproterone acetate 50–100 mg od is useful to treat the hot flushes associated with LHRH analogue. As monotherapy there is a risk of liver damage and it is less effective than LHRH analogue.
See Appendix 3 for bone densitometry indications.
Therapy for painful bone metastases

Local radiotherapy to the painful area is the treatment of choice. Usually an 8 Gy
single fraction is recommended, although five fractions may be need when re-
treated. Other therapies include:-

Small cell carcinoma .

Exclude a small cell tumour of the bladder with prostatic infiltration. For patients with
apparently localized disease is initial chemotherapy, for up to 6 cycles, with CAV
(cyclophosphamide, doxorubicin, vincristine), ACE (doxorubicin, cyclophosphamide,
etoposide) or EP (etoposide, cisplatin), followed by radiotherapy to a dose of
55Gy/20 fractions over 4 weeks. For patients with metastatic disease at
presentation chemotherapy alone is more appropriate unless there is concern
regarding the risk of uncontrolled local progression when a palliative radiotherapy
treatment schedule to the prostate can be offered.
Prostatic ductal carcinoma.
This is an aggressive tumour which should be managed along the lines of a
transitional cell carcinoma. Fit patients with apparently localized disease should be
Guidelines for the Management of Prostate Cancer offered radical radiotherapy (55Gy/20 fractions). For advanced disease consider chemotherapy with cisplatin/gemcitabine or M-VAC. In elderly and unfit patients a trial of androgen deprivation therapy is appropriate. Guidelines for the Management of Prostate Cancer Follow up

Following treatment patients should be given an appointment for review in the
appropriate clinic Thereafter follow up will be 3 to 6 monthly for first year, 6 monthly
year two – four and thereafter, if conditions stable, annual follow up.

If the condition is stable, consider referral back to Primary Care.
Guidelines for the Management of Prostate Cancer Appendices
Appendix 1
Clinical Trials supported by the network Guidelines for the Management of Prostate Cancer Appendix 1 – Prostate histology, grading
 Gleason
Grading systems have been shown to correlate with tumour stage, incidence of seminal vesicle and lymph node involvement, occurrence of distant metastases and survival. However, the reproducibility of such systems is not perfect and there is considerable intra- and inter-pathologist variability (Gallee et al, 1990) The histological grading system most commonly used is that described by Gleason (Gleason et al, 1974) and is given on adenocarcinoma and its variants. Unlike other grading systems, emphasis is placed on the assessment of the architectural growth pattern and degree of glandular differentiation, rather than cytological features, thus enabling grading to be performed at low or medium power magnification. Five tumour grades 1-5 are recognised (with sub-divisions to form 9 originally described patterns), forming a continuous spectrum of appearances from grade 1 being the well differentiated to grade 5, the most poorly differentiated. A simplified description of the histological appearances is given here: Gleason Grading of Prostate Cancer – summary of histological appearances:  Grade 1 Uniform closely packed separate glands forming a circumscribed nodule  Grade 2 Slightly less uniform, separate glands, more loosely packed, with a  Grade 3 Single separate infiltrating often angulated glands (3A), very small infiltrating glands (3B) or circumscribed cribriform or papillary masses (3C)  Grade 4 Fused raggedly infiltrating glands (4A), which may also consist of large pale cells ‘hypernephroid’ cells (4B)  Grade 5 Solid rounded masses with necrosis (5A) or ragged infiltrating tumour The majority of tumours do not have a uniform appearance, therefore the primary grade is assigned to the pattern which is predominant, and the secondary grade to the next most frequent. The Gleason score is the sum of the primary and secondary grades, unless only one tumour grade is represented, when the score is then simply the grade doubled. This gives a Gleason score range of 2-10. If a third less frequent grade is present, this is the tertiary grade and should be clearly reported if this is of higher grade than the primary and secondary grades. Modifications to the scoring system to incorporate higher grades into the Gleason score have been proposed for needle biopsy reports (e.g. Pan et al, 2000) because of the worse prognosis conferred by the presence of poorly differentiated elements. If a ‘modified’ method of Gleason score is used (i.e. including the tertiary higher grade element in the score), this should be clear from the text of the report. ‘Modified’ scores are not used in reporting radical prostatectomy specimens. A Gleason grade should be assigned, even for small tumour foci. However, Gleason grading of tumours showing therapy related changes is not possible, unless sufficient areas can be identified within the tumour which do not show these artefacts. Gleason scores of less than 5 are not usually made in assessing needle core biopsies, since entire tumour nodules are not represented in the fine cores. For biopsies from different sites, the Gleason scores at those sites should be stated. Guidelines for the Management of Prostate Cancer
Appendix 2 - Staging
TNM Classification of Prostate Cancer (TNM 2002 edition)

Clinically unapparent tumour, impalpable and not visible by imaging
Tumour an incidental finding in <5% of resected tissue Tumour an incidental finding in > 5% of resected tissue Tumour identified by needle biopsy (e.g. because of raised PSA) Tumour confined within prostate
Tumour involves > half a lobe but not both lobes Tumour extends through the prostate capsule
Unilateral or bilateral extracapsular extension Tumour is fixed or invades adjacent structures – i.e. bladder neck,
external sphincter or rectum, levator muscles or fixed to pelvic side wall

Regional Lymph Nodes

Distant Metastases

Whitmore-Jewett Staging System

Microscopic focus of well-differentiated adenocarcinoma in up to three foci of transurethral specimens or enucleation; clinically not apparent on rectal exam. Tumour not well differentiated or present in more than three areas Asymptomatic palpable nodule <1.5cm; normal surrounding prostate; no capsular extension; normal acid phosphatase Diffuse involvement of gland; no capsular extension; normal acid phosphatase with penetration through the capsule; contiguous spread may involve seminal vesicles, bladder neck, lateral side wall of pelvis; acid phosphatase may be elevated; normal bone scan Metastases to pelvic lymph nodes below aortic bifurcation; PSA may be elevated Bone or lymph node metastases above aortic bifurcation or other soft tissue. Guidelines for the Management of Prostate Cancer Appendix 3 – Osteoporosis Guidelines

Dr Helen Patterson, Professor Juliet Compston.

This recommendation relates to patients on:
1. Indefinite LHRH analogue therapy or 2. Three years of adjuvant androgen deprivation following radical radiotherapy. Bone densitometry (hip and lumbar spine) should be requested at the time the decision to initiate LHRH analogue therapy is made and at 2 yearly intervals if androgen deprivation therapy is continued if initial densitometry satisfactory. If the T score is -2 or worse at initiation of LHRH analogues then patients should commence treatment with oral bisphosphonates e.g. Alendronate 70mg po once weekly or Risedronate 35mg po once weekly with calcium and vitamin D supplementation eg Adcal-D3 one tablet b.d., Calcichew D3 forte one b.d. or Calcit D3 one b.d. A repeat DEXA scan should be repeated at 5 years to reassess the need for continued bisphosphonate and supplement treatment. If the T score is -2 or worse perform lateral thoracic and lateral lumbar spine films to exclude a pre-existing crush vertebral fracture as 2/3 do not come to medical attention, and patients who experience a vertebral fracture have a 20% incidence of a further fracture over the ensuing 12 months. If a fracture is identified, commence treatment as above with oral bisphosphonates, calcium and vitamin D. If the T score is between -1 and -2 patients should have repeat densitometry at 2 years and thereafter every 2 years and if higher than -1 repeat at 3 years to monitor progress. In addition, any patient considered to be at increased risk (see below) of osteoporosis, prior to the commencement of LHRH analogue therapy, should also be considered for bisphosphonate therapy. Past history of fragility fracture. Concurrent corticosteroid therapy. Low body mass index <19kg/m2. Heavy smoking. High alcohol intake. There are national guidelines which state that anyone over the age of 65 years started on any dose of oral corticosteroid expected to be continued for more than 3 months should be offered oral prophylaxis against osteoporosis with a bisphosphonate, either Alendronate 70mg once weekly or Risedronate 35mg once weekly together with calcium and vitamin D supplementation as above. Guidelines for the Management of Prostate Cancer Patients expected to undergo short-term LHRH analogue therapy (neo-adjuvant and concurrent with radical radiotherapy alone) do not need to undergo routine bone densitometry. For patients who are on treatment for known osteoporosis, LHRH analogue therapy should still be considered the treatment of choice to accompany their radical radiotherapy treatment unless other issues indicate the use of bicalutamide. Guidelines for the Management of Prostate Cancer Appendix 4 - Clinical Trials
The Manual for Cancer Services 2004 states that one of the responsibilities of the
MDT Lead Clinician is ‘To ensure mechanisms are in place to support entry of
eligible patients into clinical trials
…’. The infrastructure to support clinical trials
activity is the responsibility of the West Anglia, Norfolk & Waveney and Ipswich
locality of the Mid-Anglia Cancer Research Networks (WACRN, NWCRN and
MACRN) which provide facilities enabling patient entry into clinical trials in all of its
The Anglia Cancer Network Urology SSG committed to participation in high quality
research studies and clinical trials. Whenever possible, patients should be
considered for inclusion in local and national research studies and clinical trials.
There is an NSSG agreed single list of clinical trials and research studies supported
by the individual MDTs. This is updated at least annually. Further details and
protocols are available as follow:
Trust Contact Telephone Email
Addenbrooke’s West
Appendix 5 – Prostate Cancer Pathway
Patient informed of
Palliative Care
Therapy (ADT)
Consultant upgrade points
e.g. referral meets NICE criteria; at first seen, Palliative Care
during or after diagnostic tests; on or before MDT date & decision to treat date +62 days Consider Clinical Trial and Follow Up
Referral to extended MDT services at any point in pathway e.g. Palliative care specialists, Specialist Nurses and AHPs, education about adverse effects of treatment; access to help and advice from all specialists; staff alert to psychosocial needs;
therapists/local healthcare teams, Community Matron, Pharmacists (medicines usage review), Social Services, Mental Health Services, Housing benefits (Social Care and other agencies), GPs, Expert Patient Programme, Smoking Cessation, Alcohol Service (NORCAS), Voluntary organisations, information on prescription, Homeshield (over 60s) (Referral)
(1st seen)
(LMDT meeting)
(2nd treatment)
Elapsed time for follow up or presentation of recurrence, mets or predetermined gap between treatments
For comments / amendments to these guidelines, please contact:
Clinical Panel

Name Hospital Tel.

For copies of guidelines, please refer to the Anglia Cancer Network website:

These guidelines are the property of:
Anglia Cancer Network
Gibson Centre, Newmarket Hospital
Exning Road
Suffolk CB8 7JG
Tel: 01638 608209
Fax: 01638 608223



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