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Anglia Cancer Network Guidelines for the Management of Prostate Cancer Guidelines for the Management of Prostate Cancer (14-1C-113g) I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.2 Prostate INTERIM Updated, Approved and Published: May 2014 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Title: Guidelines for the Management of Prostate Cancer Authors: Vivekanandan Kumar and Rob Brierly Document management Document ratification and history Date placed on electronic library: Approved by: Urology NCG Co-Chair s Review period: 2 years (or earlier in the light of new evidence) Amended items Prostate Biopsy update (Feb 2014) Management of erectile function post radical prostatectomy and radiotherapy (Feb 2014) Authors: Vivekanandan Kumar and Rob Brierly Version number as approved and published: 2014 v2.2 May 2014 Document Owner: Anglia Cancer Network www.angliacancernetwork.nhs.uk Unique identifier no.: AngCN-U EoE SCN Cancer The process of review, update and approval of this document has been signed-off by Dr Rory Harvey, the EoE SCN, Clinical Director for Cancer. June 2014 For comments / amendments to these guidelines, please contact: Name Vivekanandan Kumar Robert Brierly Hospital Tel. No Email NNUH [email protected] Ipswich [email protected] For copies of guidelines, please refer to the Anglia Cancer Network website: www.angliacancernetwork.nhs.uk Monitoring the effectiveness of the Process a) Process for Monitoring compliance and Effectiveness - Review of compliance as determined by audit. Any non compliance to be presented by PQ Manager to the AngCN Business Meeting on an annual basis – the minutes of this meeting are retained for a minimum of five years. b) Standards/Key Performance Indicators – This process forms part of a quality system working to, but not accredited to, International Standard BS EN ISO 9001:2008. The effectiveness of the process will be monitored in accordance with the methods given in the quality manual, AngCN-QM Disclaimer It is your responsibility to check against the electronic library that this printed out copy is the most recent issue of this document. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 2 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer CONTENTS Page No INTRODUCTION ........................................................................................................................... ……… 4 REFERRALS ........................................................................................................................................... 4 PROSTATE BIOPSY ............................................................................................................................... 4 LMDT REVIEW........................................................................................................................................ 5 STAGING ................................................................................................................................................ 5 DEFINING TUMOUR STAGE AND GRADE ........................................................................................... 5 MANAGEMENT OPTIONS FOR EARLY PROSTATE CANCER ........................................................... 5 1. Active Surveillance 6 2. Radical Prostatectomy 6 3. Radioactive seed implantation – Brachytherapy 7 4. External Beam Radiotherapy – EBRT ………………………………………………………… 7 6. Long term androgen deprivation therapy alone 8 MANAGEMENT OPTIONS FOR LOCALLY ADVANCED PROSTATE CANCER (WITHOUT METASTASES) T3B/T4 N0/1 M0 ........................................................................................................... 8 MANAGEMENT OF ERECTILE DYSFUNCTION POST RADICAL TREATMENTS ............................. 9 SALVAGE THERAPY FOR RECURRENT PROSTATE CANCER POST-RADIOTHERAPY ............... 9 MANAGEMENT OPTIONS FOR METASTATIC DISEASE .................................................................... 10 THERAPY FOR PAINFUL BONE METASTASES ................................................................................. 11 OTHER CONSIDERATIONS ................................................................................................................... 12 SMALL CELL CARCINOMA ................................................................................................................... 12 FOLLOW UP ........................................................................................................................................... 12 APPENDICES ......................................................................................................................................... 15 Appendix 1 – Prostate histology, grading 16 Appendix 2 - Staging 17 Appendix 3 – Osteoporosis Guidelines 18 Appendix 4 - Clinical Trials 19 Appendix 5 – Prostate Cancer Pathway (14-1C-113g) 20 I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 3 of 21 Anglia Cancer Network 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 with 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 made. These guidelines have been developed by discussion between clinicians within the Anglia Cancer Network Urology Network Cancer Group (NCG) but without the establishment of a formal guideline development group. These guidelines have been endorsed by the Anglia Cancer Network Urology NCG. 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 e.g. NICE, BAUS, EAU, AUA. Referrals For referrals from Primary and Secondary Care, see AngCN prostate cancer pathway Appendix 5 – Prostate Cancer Pathway and DH suspected cancer guidance. Prostate biopsy The following can be considered as indications for biopsy: Any patient with PSA > age adjusted upper limit (ULN) Any patient with a raised PSA needs a LUTS assessment Other men who wish to have a biopsy based on their PSA and general level of risk Any patient with palpably abnormal prostate. A minimum of ten samples should be taken to reduce the risk of underestimating tumour grade. In patients with continued suspicion of prostate cancer, after first negative biopsy, either in the form of rising PSA, change in DRE findings or MRI changes, a TRUS + Trans perineal template, biopsies should be considered for subsequent biopsy to reduce false negative results, especially from the anterior part of the prostate gland and reduce underestimating the cancer grade of the cancer if found. An MRI before repeat biopsies should be considered after discussions with the local MDT. See AngCN Pathology guidelines for details of pathology assessment of biopsy material. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 4 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer 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. 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 Staging Bone scintigram in all patients in intermediate and high risk categories, or if bone pain. MR pelvis should be considered in all patients being considered for radical therapy and in all patients considered for active surveillance. MRI should be performed at least three weeks after biopsy (dependent on individual centre) 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 In the UK the TNM is used (see Appendix 2) Management options for early prostate cancer Patients will have been assigned a D’Amico Risk Category – low, intermediate or high. For most patients with early stage prostate cancer there are will be a number of options available. 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 initially by the local urological and oncological core members of their LMDT. The main management options include: 1. 2. 3. 4. 5. 6. Active surveillance Radical prostatectomy Radioactive seed implantation - Brachytherapy External Beam Radiotherapy Watchful wait Hormone therapy alone I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 5 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer 1. Active Surveillance Type of patient who may be considered: >10 years life expectancy Gleason sum 6 or 7(3+4) (well/moderately well differentiated) tumours T1/T2a and T2b PSA<10 Asymptomatic Patient preference Men with intermediate risk cancer who do not wish to have immediate radical treatment Baseline MRI should be considered for all patients contemplating active surveillance. The risk of progression is related to grade and stage. These risks should be explained to the patient. If the patient opts for active surveillance and he is suitable for radical treatment should 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 should involve repeat prostate biopsies every 12 to 18 months. The patients 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 surveillance PDAdt between 10 months and 4 years – consider treatment according to patient parameters (i.e. Radical or palliative treatment). Progression in repeat biopsies (eg. grade shift, increased tumor volume) should trigger intervention Patients with less than 10 years of life expectancy, older or serious medical conditions should be offered watchful wait. 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 these men will be aged under 73 years. T1/T2N0M0 and PSA < 20 ug/l Some men with operable cT3 disease may wish for 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 counseling, supplemented by information sheets. In the event of an unrecordable PSA post-operatively there is no randomised evidence that early post-operative RT offers advantage compared to early salvage RT. Indications for referral to a Clinical Oncologist (outside of clinical trials) to discuss RT includes a PSA which fails to become unrecordable or a rising PSA post-operatively. Salvage I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 6 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer RT is most successful when the PSA is <0.2ng/ml (RFS 64%), however early referral for discussion after one or two PSA rises is advised. There is no randomized evidence for the use of androgen deprivation post-operatively outside of clinical trials 3. Radioactive seed implantation – Brachytherapy Patients may be considered with the following factors: No greater than half the cores or sites (for TP biopsies) and <50% of biopsy material in positive cores/sites PSA <15 ug/l if Gleason 6 (3+3) and 10 ug/l if Gleason 7(3+4) T1N0M0 or T2N0M0 Minimal lower urinary tract symptoms (LUTS) - IPSS < 12/35 / flow ≥15ml/s or IPSS <10 / flow >10ml/s () Prostate volume ≤65ccm by MRI criteria. Patient preference o In patients with significant LUTS de-obstructing surgery prior to brachytherapy can be considered after review in brachy centre o Patients after TURP/HoLEP can be considered after review in brachy centre Patients should be referred to the Specialist Multi-Disciplinary Team at Addenbrookes Hospital 4. External Beam Radiotherapy – EBRT There are four RT centres in Anglia (Cambridge, Ipswich, Norfolk & Norwich and Peterborough). All now have access to the advanced RT techniques of Intensity Modulated Radiotherapy (IMRT) and Image-Guided Radiotherapy (IGRT). The verification protocols and planning target volumes for radical treatments used are agreed by individual departments. Criteria for patients undergoing EBRT T1-3b N0 M0 Any Gleason grade Life expectancy > 10 years in low/intermediate risk disease Consider life expectancy > 5 years in high risk disease No history of radio sensitivity or previous pelvic radiotherapy. Contraindications to brachytherapy or radical prostatectomy. Patient preference. Radiotherapy and androgen deprivation therapy recommendations: a) Radical radiotherapy without associated androgen deprivation therapy pT1a/pT1c (10% sample volume) and Gleason <7 and PSA in normal range Normal potency Patient preference b) Neoadjuvant (3-6 months) and concurrent androgen deprivation pT1b/c-clinical T2a/b/c Gleason < 8 I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 7 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer PSA < = 20 ug/l c) Adjuvant androgen deprivation Consider extending the period of androgen deprivation to 3 years for men with high risk localized prostate cancer and discuss the benefits and risks of this option with them. 5. Watchful Waiting This approach aims to avoid treatment or delay as long as possible. Consider in patients with localized disease who have no symptoms and due to co-morbidities are unsuitable for radical treatment options. 6. Long term androgen deprivation therapy alone Patients who may reasonably be considered include: Life expectancy less than 10 years. Significant urinary symptoms may increase the advantages of offering androgen deprivation. No other significant risk factor for osteoporosis Patient preference. The options for androgen deprivation are: LHRH agonists – goserelin, leuprorelin, triptorelin (intermittent therapy may be considered, particularly for low volume minimal metastatic disease with a low PSA after 6 to 9 months of treatment). LHRH antagonists – degaralix (Limited indication according to local protocol) Orchidectomy 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. Patients intending to pursue long term ADT (including adjuvant) should be considered for bone densitometry at the start of their treatment and then at two 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 densitometry report. See Appendix 3. Management options for locally advanced prostate cancer (without metastases) T3b/T4 N0/1 M0 Androgen deprivation plus EBRT (T3/4 N0 M0) Androgen deprivation alone Watchful waiting (co-morbidity/patient preference) Radical prostatectomy or brachytherapy are seldom appropriate for patients with stage cT3b disease or more advanced disease. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 8 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Management of Erectile Dysfunction Post Radical Treatments Penile rehabilitation is defined as the use of any drug or device at or after radical prostatectomy to maximize the recovery of erectile function. The purpose of penile rehabilitation is the prevention of corpus cavernosum smooth muscle structural alterations, to limit venous leak development during the period of recovery from neuropraxia, and therefore to maximize the chances of a man returning to his preoperative level of erectile function. Recent studies suggest a benefit from early pharmacological rehabilitation after radical prostatectomy. Proposed guideline : a) Pre-op good Erectile function,( IIEF >16/25), Good unilateral / bilateral nerve spare: Cialis (tadalfil) 5mg Once Daily (preferred treatment) Review in 3 months if no early response, consider change to MUSE/ Intracavernosal Injection alprostadil / Vacuum tumescence device. Consider continuing any PDE5 after 3 months as return of normal erections can be delayed up to 24 months Consider use of Vacuum device in combination with PDE5 If at 3 months review there is early response to PDE5 – Cialis or Sildenafil then change over to PRN dose b) Pre-op ED or IIEF <16/25 or poor nerve spare: Direct MUSE/ Intracavernosal Injection alprostadil / Vacuum tumescence device. There is less evidence for management of ED post radiotherapy. However the above should still be considered to offer potential benefit and has been recommended by NICE guidance (2014). Men should be provided with early and ongoing access to specialist erectile dysfunction services including psychosexual counseling. Androgen deprivation therapy and erectile dysfunction NICE guidance (2014) recommends that men should be offered access to specialist erectile dysfunction services including psychosexual counseling as well as treatment with PDE5 inhibitors for loss of erectile function on hormone treatments. Department of Health Guidance DoH guidance(5) (HSC1999/148) on treatment of erectile dysfunction states: “the Department advises doctors that one treatment a week will be appropriate for most patients treated for erectile dysfunction. If the GP in exercising his clinical judgement considers that more than one treatment a week is appropriate he should prescribe that amount on the NHS.” Salvage Therapy for Recurrent Prostate Cancer Post-Radiotherapy I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 9 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer In the event of biochemical recurrence after EBRT, salvage therapy may be considered. Local salvage local therapies (includes prostatectomy, cryotherapy, HIFU & HDR brachytherapy) are associated with clinically significant toxicity and counseling of the patient is essential. There are no randomized clinical trials comparing outcomes with observation, but a systematic review showed similar biochemical recurrences but differing toxicities between options. There are no formal criteria established to determine who will benefit most from salvage therapy, however the following parameters may predict poorer outcome High risk disease at time of original diagnosis Short time interval to biochemical relapse (< 18 months) Short PSA Doubling time (<8 months) A serum PSA > 10 ng/ml at time of salvage consideration Referral to a centre of expertise in salvage options and use of clinical trials is recommended. Local imaging to establish no evidence of nodal or bone disease should be performed. Additional imaging may be undertaken at referral centres (eg whole body MRI, Choline-PET) before embarking on salvage therapy. Egs Mount Vernon Hospital HDR Brachytherapy (Prof Peter Hoskins) UCL London HIFU (Prof Mark Emberton) Guildford Cryotherapy (Mr John Davies) 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. Castration Sensitive Metastatic Prostate Cancer The gold standard (outside of clinical trials) for first line treatment is an LHRH agonist with antiandrogen given initially to prevent disease flare. Although androgen deprivation therapy (ADT) is palliative, it can normalize serum levels of prostate specific antigen (PSA) in over 90% of patients and can produce objective tumor responses in 80-90%. This antitumor activity can improve quality of life (QOL) by reducing bone pain as well as the rates of complications (eg, pathologic fracture, spinal cord compression, ureteral obstruction). The duration of response to ADT for patients with metastatic disease is highly variable, and most prostate cancer patients eventually experience disease progression despite treatment. Patients who have progressed while on ADT are said to have castration resistant disease, although such tumors may remain responsive to additional therapies directed against androgenic stimulation of the prostate cancer. Castration Resistant Metastatic Prostate Cancer (CRPC) I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 10 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Patients should remain on ADT despite rising PSA. The use of additional treatments should be considered on the basis of symptoms, DT PSA, and an individual patients co-morbidities rather than asymptomatic PSA change alone. Referral/discussion with Oncologists (if followed up in Urology Clinics until this point) should be considered. At the time of writing there is no evidence/consensus regarding the sequencing of both older and newer therapies in the CRPC setting. The availability of funding (CDF/NICE approval) for newer therapies remains under review. ‘Older Endocrine Options’ Maximum androgen blockage Bicalutamide 50mg od Antiandrogen withdrawal (~20% men progressing on MAB will have PSA/symptomatic response to withdrawal of antiandrogen) Glucocorticoids eg prednisolone 10mg od, Dexamethasone 0.5mg od Diethylstilboestrol 1mg od (+aspirin) ‘Newer Endocrine and Chemotherapy Options’ Table from NHS England draft document An algorithm for possible sequencing is listed in Appendix 6 Therapy for painful bone metastases External beam radiotherapy remains treatment of choice for painful bone metastases. A single 8Gy fraction is recommended unless considering scenarios of re-treatment/spinal cord compression. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 11 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Radium 223 is now available (Sept 2014) via CDF application and administered via Nuclear Medicine Dept. It is indicated in CRPC post-docetaxol for symptomatic bone metastases with no visceral metastases. Strontium 89 Surgical decompression Internal fixation Bisphosphonates Other Considerations Consider bilateral breast bud irradiation in patients with CRPC prior to commencement of diethystilboestrol to minimize development of tender gynaecomastia. It is not effective for established gynaecomastia. 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. Small cell carcinoma If patient has pure small cell carcinoma of the prostate serum levels of PSA do not correlate with disease activity. Some patients may have combination of small cell and adenocarcinoma where ADT may also be required. Exclude a small cell tumour of the bladder with prostatic infiltration. Localised disease – initial treatment is with ‘small cell’ chemotherapy eg Carboplatin/Etoposide EP or Cyclophosphamide, Doxorubicin, Vincristine (CAV) followed by radiotherapy to a dose of 55Gy/20 fractions over four weeks. 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. . Follow up Follow up arrangements have been determined at each hospital in conjunction with primary care trusts. If the condition is stable, consider referral back to Primary Care. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 12 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer PSA Guidance for General Practitioners Nk Two Week referral for suspected prostate cancer 1. 2. An elevated age specific PSA* in men with a 10 year life expectancy A high PSA (>20ng/mL) in men with a clinically malignant prostate or bone pain (*if the PSA is marginally elevated, a second PSA, two weeks later, may be helpful before referral) *Age Specific PSA (NICE Guidelines 2005) Age 50 to 59 years PSA ≤ 3 ng/mL Age 60 to 69 years PSA ≤ 4 ng/mL Age 70 years or older PSA ≤ 5 ng/mL Risk Stratification of Prostate Cancer (at diagnosis) Level of risk PSA (ng/mL) Gleason score Stage Low risk <10 and ≤6 and T1-T2a Intermediate risk 10-20 or 7 or T2b High risk >20 or 8-10 or ≥T2c or N+ or M+ T1: not palpable; T2a: organ confined, < 50% of 1 lobe; T2b: organ confined, >50% of 1 lobe; T2c: organ confined, both lobes; T3a/b: through capsule/ into seminal vesicles; PSA follow up during Active Surveillance (for patients who are candidates for treatment with curative intent if disease progresses) Criteria for Discharge Primary Care follow up Trigger for Re-referral • Secondary care follow-up • Not applicable • Not applicable PSA follow up after Radical Prostatectomy Criteria for Discharge Primary Care follow up Trigger for Re-referral • PSA <0.1ng/mL • Low risk: six monthly PSA for five years then annually for five years • PSA ≥ 0.2ng/mL • Intermediate/High risk: six monthly PSA for ten years • 2 consecutive rises above 0.02ng/mL • Asymptomatic (for patients managed with 1 standard PSA test) 1 (for patients managed with super-sensitive PSA test) • Symptomatic 1 Costs: standard PSA = £6.29; super-sensitive PSA = £28.02. Source: NNUH Feb 2015 PSA follow up after Radical Radiotherapy/Brachytherapy Criteria for Discharge Primary Care follow up Trigger for Re-referral • PSA < 2ng/mL or stable PSA • Six monthly PSA for five years • Asymptomatic • Annual PSA year 6 onwards • PSA > 2ng/mL above nadir (the “nadir” is the lowest recorded PSA since diagnosis) Intermediate and high risk patients may remain under secondary care follow-up until off hormones Intermediate and high risk patients may need extended adjuvant hormone treatment for up to three years as recommended on letter to GP • Symptomatic (LUTS or rectal symptoms) I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 13 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer PSA follow up for patients on Hormone Treatment Criteria for Discharge Primary Care follow up Trigger for Re-referral • PSA <10ng/mL or stable PSA • Six monthly PSA • *PSA >10ng/mL • Asymptomatic • Symptomatic *Unless PSA threshold for re-referral has been stated by the urologist If PSA rising, consider starting bicalutamide 50mg once daily in addition to LHRH analogues PSA follow up for patients on Watchful Waiting (in men >80 years of age or with a life expectancy of less than 10 years) Criteria for Discharge • PSA <20ng/mL or stable PSA • Asymptomatic Primary Care Follow Up • Six monthly PSA for five years then annually if deemed appropriate Trigger for Referral to Urology • *PSA >20ng/mL • Symptomatic *Unless PSA threshold for re-referral has been stated by the urologist Persistently raised PSA after normal biopsies (incl HGPIN) or with stable serial PSA Men with a life expectancy of greater than 10 years Criteria for Discharge Primary Care follow up Trigger for Re-referral • Normal biopsy with a stable PSA • Six monthly PSA • Increase in PSA of 25% in 6 months or 50% in 12 months (i.e. a PSA doubling time of <2 years) • Asymptomatic • 2 consecutive rises • the PSA threshold for re-referral may be stated by the urologist Men with a life expectancy of less than 10 years Criteria for Discharge Primary Care follow up Trigger for Re-referral • Normal biopsy with a stable PSA • Six monthly PSA for five years • PSA >20ng/mL • Asymptomatic • Annual PSA year 6 onwards • Symptomatic If PSA > 20ng/ml at referral to GP, the PSA threshold for re-referral should be stated by the urologist THIS IS A GUIDELINE ONLY INDIVIDUALISE YOUR FOLLOW-UP SCHEDULES ACCORDING TO EACH PATIENT’S CIRCUMSTANCES As a patient ages or their co-morbidities change, their treatment group should be adjusted accordingly. For example, a patient who underwent a radical prostatectomy at the age of 69 years, who is found to have a PSA recurrence at age 81 years, would probably be best managed with watchful waiting. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 14 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Appendices Appendix 1 Prostate Histology, grading Appendix 2 Staging Appendix 3 Osteoporosis Guidelines Appendix 4 Clinical Trials supported by the network Appendix 5 Prostate Cancer Pathway (14-1C-113g) Appendix 6 Draft National Chemotherapy Algorithm I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 15 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Appendix 1 – Prostate histology, grading Gleason Score 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 partially circumscribed margin 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 (5B) 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. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 16 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Appendix 2 - Staging TNM Classification of Prostate Cancer (TNM 2002 edition) TO TX No evidence of primary tumour Primary tumour cannot be assessed T1 Clinically unapparent tumour, impalpable and not visible by imaging T1a Tumour an incidental finding in <5% of resected tissue T1b Tumour an incidental finding in > 5% of resected tissue T1c Tumour identified by needle biopsy (e.g. because of raised PSA) T2 Tumour confined within prostate T2a Tumour involves < half one lobe T2b Tumour involves > half a lobe but not both lobes T2c Tumour involves both lobes T3 Tumour extends through the prostate capsule T3a Unilateral or bilateral extracapsular extension T3b Tumour invades seminal vesicle(s) T4 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 NX Nodes cannot be assessed N0 No regional lymph node metastases N1 Regional lymph node metastasis Distant Metastases MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Metastasis I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 17 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Appendix 3 – Osteoporosis Guidelines GUIDELINES FOR THE PREVENTION AND MANAGEMENT OF OSTEOPOROSIS IN PATIENTS WITH PROSTATE CANCER EXPECTED TO RECEIVE PROLONGED ANDROGEN DEPRIVATION. 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. 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. I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 18 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Appendix 4 - Clinical Trials The Manual for Cancer Services 2004 (updated 2011/12) 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 within the Anglia is the responsibility of the newly formed Clinical Research Network: Eastern (1st April 2014). Division 1 of this network will focus on Cancer and replaces the previous West Anglia Cancer Research Network (WACRN) and Anglia East Cancer Research Network (AECRN). In addition, the footprint of the new CRN Eastern also includes Colchester in Essex and East/North Herts Trusts in Herts & Beds. For further details, please contact: Kath Jones (Research & Development), Clinical Research Network: Eastern. Norfolk and Norwich University Hospital, ([email protected]) I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 19 of 21 Anglia Cancer Network Guidelines for the Management of Prostate Cancer Appendix 5 – Prostate Cancer Pathway (14-1C-113g) PROSTATE CANCER PATHWAY (E&W) Final Other Referrals i.e. non urgent 18ww referral Tertiary Referrals Active Monitoring SPECIALIST MULTIDISCIPLINARY (SMDT) MEETING OPA Decision to treat (DTT) Recurrence detected Brachytherapy Cryotherapy Urgent GP suspected cancer referral (2WW) Prostate Clinic with biopsy LOCAL MULTIDISCIPLINARY TEAM (LMDT) MEETING Histology discussed. Staging investigations requested, if appropriate. RRP Patient informed of diagnosis (OPA / telephone) - Decision to treat (DTT) - Patient referred to SMDT if appropriate (i.e. if patient chooses brachytherapy/ surgery) L/SMDT / OPA to assess fitness for subsequent treatment Radiotherapy +/- Androgen Deprivation Therapy (ADT) Staging MRI / Bone/CT LMDT MEETING Earliest clinically appropriate date, decision to treat (DTT) ADT Adjuvant Radiotherapy Palliative Care Androgen Deprivation Therapy (ADT) Active Monitoring Consultant upgrade points e.g. referral meets NICE criteria; at first seen, during or after diagnostic tests; on or before MDT date & decision to treat date +62 days from these upgrade point dates Palliative Care 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) Day 0 (Referral) Key: By Day 14 (1st seen) Unit / Centre Centre Access to specialist services By Day 28 (LMDT meeting) GFOCW I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.2 Prostate INTERIM By Day 42 (DTT) Day 0 (DTT) By Day 62 (treatment) Elapsed time for follow up or presentation of recurrence, mets or predetermined gap between treatments Updated, Approved and Published: May 2014 By Day 31 (2nd treatment) I:\CPC1\MEDICAL DIRECTORATE\SCN Team\4. Cancer 13\NCGs\Urology\Key documents (all areas)\AngCN Key documents 2014\Current documents\AngCN-NCG 2014 v2.7 Prostate FINAL.doc Page 21 of 21