management of organ-confined (localised) prostatic carcinoma

Last edited 06/2019

TNM (Tumour, Node, Metastasis)

• in the TNM staging system, localised prostate cancer is the same as one of the following:
  • T1, N0, M0
  • T2, N0, M0

NICE suggest that urological cancer Multidisciplinary teams should assign a risk category to all newly diagnosed men with localised prostate cancer (1)

This is based on the PSA, Gleason score and clinical stage of the prostate cancer.

*High-risk localised prostate cancer is also included in the definition of locally advanced prostate cancer.

The therapeutic options include:

• conservative approach
  • watch and wait:
    • this approach may be acceptable if the estimated life expectancy is less than 10 years and the histology of the tumour is non-aggressive
    • NICE suggest that (1):
      • a member of the urological cancer MDT should review men with localised prostate cancer who have chosen a watchful waiting regimen and who have evidence of significant disease progression (that is, rapidly rising PSA level or bone pain)
      • men with prostate cancer who have chosen a watchful waiting regimen with no curative intent should normally be followed up in primary care in accordance with protocols agreed by the local urological cancer MDT and the relevant primary care organisation(s). Their PSA should be measured at least once a year

• active management

  • Low-risk localised prostate cancer

    • NICE suggest that (1):
      • choice between active surveillance, radical prostatectomy or radical radiotherapy to people with low-risk localised prostate cancer for whom radical treatment is suitable
        
        

  Active surveillance

  • active surveillance should be offered as an option to men with low-risk localised prostate cancer for whom radical prostatectomy or radical radiotherapy is suitable
  • consider using the protocol in table below for men who have chosen active surveillance
  • consider active surveillance for men with intermediate-risk localised prostate cancer who do not wish to have immediate radical prostatectomy or radical radiotherapy
  • do not offer active surveillance to men with high-risk localised prostate cancer
    
    

  Comparison of Active Surveillance versus Watchful Waiting

  Active surveillance

  Watchful waiting

  part of a 'curative' strategy and is aimed at people with localised prostate cancer for whom radical treatments are suitable, keeping them within a 'window of curability' whereby only those whose tumours are showing signs of progressing, or those with a preference for intervention are considered for radical treatment. active surveillance may thus avoid or delay the need for radiotherapy or surgery.

  part of a strategy for 'controlling' rather than 'curing' prostate cancer and is aimed at people with localised prostate cancer who do not ever wish to have curative treatment, or it is not suitable for them involves the deferred use of hormone therapy watchful waiting avoids the use of surgery or radiation, but implies that curative treatment will not be attempted.

   

  Protocol for active surveillance

  Timing	Tests a
  Year 1 of active surveillance	Every 3 to 4 months: measure prostatespecific antigen (PSA)b Throughout active surveillance: monitor PSA kineticsc At 12 months: digital rectal examination (DRE)d At 12 to 18 months: multiparametric MRI
  Year 2 and every year thereafter until active surveillance ends	Every 6 months: measure PSAb Throughout active surveillance: monitor PSA kineticsc Every 12 months: DREd

  Key:

  a If there is concern about clinical or PSA changes at any time during active surveillance, reassess with multiparametric MRI and/or re-biopsy.

  b Could be carried out in primary care if there are agreed shared-care protocols and recall systems.

  c Could include PSA density and velocity.

  d Should be performed by a healthcare professional with expertise and confidence in performing DRE. In a large UK trial that informed this protocol, DREs were carried out by a urologist or a nurse specialist.

  
  
  

  • Intermediate-risk localised prostate cancer

    • offer radical prostatectomy or radical radiotherapy (external beam radiotherapy + brachytherapy)
    • consider active surveillance for people who choose not to have immediate radical treatment
      
      
  • High-risk localised prostate cancer
  • do not offer active surveillance to people with high-risk localised prostate cancer
  • offer radical prostatectomy or radical radiotherapy to people with high-risk localised prostate cancer when it is likely the person's cancer can be controlled in the long term
    
    
  • Radical treatment - localised prostate cancer (1)
    • radical prostatectomy:
      • may be curative
      • possible uwanted effects of prostatectomy include severe haemorrhage, thromboembolism, anastomotic stricture, fistula, ureteric injury, lymphocele, rectal injury and, later, erectile dysfunction (in up to 60% of men) and incontinence (2)
      • there is evidence from the Scandinavian Prostate Cancer Group Study Number 4 (3) that, in men with early prostate cancer, radical prostatectomy reduced deaths from prostate cancer but did not reduce overall mortality more than watchfull waiting. In this study prostatectomy was associated with more erectile dysfunction and urinary leakage but did not adversely affect self assessed quality of life (4)
      • a more recent study has also provided evidence that in men with early prostate cancer, radical prostatectomy reduced death from prostate cancer, distant metastasis, local progression from any cause more than watchful waiting over 10 years follow-up (5). However a commentary on this study suggests that any extrapolation to contemporary practice must be tempered with caution because of changes in prostate cancer management since the conception of the study e.g. men in the watchful waiting arm of the study who developed local progression were not offered any treatment until late in the study period (2003) (6)
        
        
    • external beam radiotherapy
      • external beam radiotherapy is given on an outpatient basis over about 8 weeks
      • common unwanted effects arising during or within 90 days after radiotherapy include mild urinary frequency and urgency, diarrhoea and fatigue. Possible delayed, long-term effects include erectile dysfunction (in up to 50% of patients); gastrointestinal toxicity including radiation proctitis (around 3-12%); rectal bleeding (around 7%; severe in around 0.8%); mucous discharge or diarrhoea (around 1.8%); urinary incontinence; haematuria; urinary frequency, urgency and nocturia (around 7%); and urethral strictures (around 1%) (2)
        
        
    • radiotherapy + hormones (1)
      • people with intermediate and high-risk localised disease should be offered a combination of radiotherapy and androgen deprivation therapy
      • people with intermediate and high-risk localised prostate cancer should be offered 6 months of androgen deprivation therapy given before, during or after radical external beam radiotherapy
      • consider pelvic radiotherapy in people with locally advanced prostate cancer who have a greater than 15% risk of pelvic lymph node involvement and who are to receive neoadjuvant hormonal therapy and radical radiotherapy
      • consider continuing androgen deprivation therapy for up to 3 years for people with high-risk localised prostate cancer
        
        
    • chemotherapy
      • docetaxel chemotherapy is an option for people with newly diagnosed non-metastatic prostate cancer who are starting androgen deprivation therapy if they have high risk disease and no significant co-morbidities
        

A review concerning the management of localised prostate cancer concluded (2):

• localised prostate cancer is potentially curable with radical treatment (prostatectomy, radiotherapy, brachytherapy, or combinations of these treatments with each other or with hormone therapy)
• radical treatments (prostatectomy, radiotherapy, brachytherapy) have different long-term unwanted effects, which are weighted differently by individual men
• therefore in men with asymptomatic localised well-differentiated disease, radical treatments have not been shown to reduce overall mortality compared with conservative management, and may introduce more morbidity than the disease itself might cause

Notes:

• treatment options for locally recurrent prostate cancer after radiotherapy are limited and include salvage radical prostatectomy, salvage cryotherapy and salvage brachytherapy (8)
• high-intensity focused ultrasound and cryotherapy are not recommended for men with localised prostate cancer other than in the context of controlled clinical trials comparing their use with established interventions (1)
• PSA levels for all men with prostate cancer who are having radical treatment should be checked at the earliest 6 weeks following treatment, at least every 6 months for the first 2 years and then at least once a year thereafter (1)

Reference:

• (1) NICE (January 2019).Prostate cancer Diagnosis and treatment
• (2) Drug and Therapeutics Bulletin (2004); 42(11):81-4.
• (3) Holmber L et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. NEJM 2002; 347:781-9.
• (4) Steineck et al. Quality of life after radical prostatectomy or watchful waiting. NEJM 2002;347:790-6
• (5) Bill-Axelson A et al. Radical prostatectomy versus watchful waiting in early prostate cancer. NEJM 2005; 352:1977-84.
• (6) Commentary. Evidence-Based Medicine 2005; 10(6): 168.
• (7) NICE (May 2006).High dose rate brachytherapy in combination with external-beam radiotherapy for localised prostate cancer.
• (8) NICE (May 2005).Cryotherapy for recurrent prostate cancer