Prostate Cancer

Full Text Guidelines Summary of Changes Scientific Publications & Appendices Pocket Guidelines Archive Panel

2017

New and relevant evidence has been identified, collated and appraised through a structured assessment of the literature and incorporated in all chapters of the 2017 EAU PCa Guidelines.

Key changes for the 2017 print:

  • Chapter 3 – Epidemiology and aetiology. This section has been completely renewed.
  • Chapter 4 – Classification and staging systems. This chapter has been expanded with a new section

(4.3 Prognostic relevance of stratification). Additional information on the International Society of Urological Pathology Gleason grading has been included in Table 4.2.2 (EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer).

  • Section 6.6.8 – Imaging as marker of response in metastatic prostate cancer. This is a new section.
  • Chapter 6.7 – Management of PCa in older men. Two new figures have been included.
  • Chapter 8 – Quality of life outcomes in prostate cancer. This chapter is partly based on the findings of a new systematic review (SR) (see below). A second review is ongoing, the findings of which will be incorporated in the 2018 print of these Guidelines.

Changes in the summaries of evidence and recommendations can be found in sections:

3.2.3        Summary of evidence and guidelines for epidemiology and aetiology

Summary of evidence
Prostate cancer is a major health issue in men, the incidence mainly dependent on age.
Genetic factors are associated with risk of (aggressive) PCa but ongoing trials will need to define the clinical applicability of screening for genetic susceptibility of PCa.
A variety of exogenous/environmental factors may have an impact on the risk of progression.
5-ARIs are not EMA-approved for PCa prevention.
Selenium or vitamin-E supplements have no beneficial effect in preventing PCa.
In hypogonadal men, testosterone supplementation does not increase the risk of PCa.

 

Recommendation
No definitive recommendation can be provided for specific preventive or dietary measures to reduce the risk of developing prostate cancer.

 

Table 4.2.2: EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer

Definition
Low-risk Intermediate-risk High-risk
PSA < 10 ng/mL

and GS < 7 (ISUP Grade 1)

and cT1-2a

PSA 10-20 ng/mL

or GS 7 (ISUP Grade 2/3)

or cT2b

PSA > 20 ng/mL

or GS > 7 (ISUP Grade 4/5)

or cT2c

any PSA

any GS cT3-4

or cN+

Any ISUP Grade

Localised Locally advanced

GS = Gleason score; ISUP = International Society for Urologcal Pathology; PSA = prostate-specific antigen.

 

6.1.5        Guidelines for active surveillance and watchful waiting

Recommendations – active surveillance LE GR
Perform multiparametric magnetic resonance imaging before a confirmatory biopsy. 2b B
During confirmatory biopsy include systematic and targeted biopsies. 2a B

 

6.2.7.5     Guidelines for eLND in prostate cancer and pN+ patients

Recommendation LE GR
Do not perform a frozen section of nodes during radical prostatectomy to decide whether to proceed with, or abandon, the procedure. 2a A

 

6.2.10      Guidelines for radical prostatectomy

Recommendations LE GR
Offer both radical prostatectomy and radiotherapy in patients with low- and intermediate-risk disease and a life expectancy > 10 years. 1b A
Offer active surveillance as an alternative to surgery in patients with low-risk disease and a life expectancy of > 10 years. 1b A

 

6.3.8        Summary of evidence and guidelines for definitive radiotherapy

Summary of evidence LE
The optimum duration of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is well established in the literature. There is no evidence that these durations should change when using brachytherapy boost with EBRT. 1b
Limited data, from experienced centres only, are available for the use of fractionated high-dose-rate brachytherapy as monotherapy in patients with low and intermediate-risk PCa. 2a

 

Recommendations LE GR
Moderate hypofractionation (HFX) with IMRT including image-guided radiation therapy (IGRT) to the prostate only can be offered to carefully selected patients with localised disease (as discussed in the text). 1a A
Moderate HFX should adhere to radiotherapy-protocols from trials with equivalent outcome and toxicity, i.e. 60 Gy/20 fractions in four weeks or 70 Gy/28 fractions in six weeks. 1a A

 

6.9.4.6     Guidelines for imaging in patients with biochemical recurrence

Prostate-specific antigen (PSA) recurrence after radical prostatectomy LE GR
PSA ≥ 1 ng/mL: positon emission tomography (PET)/computed tomography (CT) imaging is recommended using choline or prostate-specific membrane antigen (PMSA). 2b A

 

8.3.1.1     Guidelines for long term quality of life in men with localised disease

Recommendations LE GR
Advise eligible patients for active surveillance, that global quality of life is equivalent for up to five years compared to radical prostatectomy or radiotherapy. 1b A
Discuss the negative impact of surgery on urinary and sexual function, as well as the negative impact of radiotherapy on bowel function with patients. 1b A
Advise patients treated with brachytherapy of the negative impact on irritative urinary symptomatology at one year but not after five years. 1b C

 

8.3.2.1     Guidelines on improving quality of life in men who have been diagnosed with prostate cancer

Recommendations LE GR
Offer men on androgen deprivation therapy, twelve weeks of supervised (by trained exercise specialists) combined aerobic and resistance exercise. 1a A
Offer men with T1-T3 disease specialist nurse led, multi-disciplinary rehabilitation based on the patients’ personal goals addressing incontinence, sexuality, depression and fear of recurrence, social support and positive lifestyle changes after any radical treatment. 1b A

2016

New and relevant evidence has been identified, collated and appraised through a structured assessment of the literature and incorporated in all chapters of the 2016 EAU PCa Guidelines.

Key changes in the 2016 print:

Chapter 4 – Classification and staging systems, the new 2014 International Society of Urological Pathology (ISUP) Consensus Conference findings have been included.

  • Section 5.2.4 Diagnosis – The role of imaging; the key findings of the systematic review on the performance of prostate pre-biopsy multiparametric MRI in predicting prostate biopsy results, have been included [3]. The recommendations have been adapted accordingly.
  • Section 6.2 – Radical prostatectomy, a new Section 6.2.6 – Indication and extent of pelvic lymph node dissection has been included.
  • Section 6.4 – Options other than surgery and radiotherapy for the primary treatment of localised PCa, has been revised and restructured.
  • Section 6.6 – Treatment: Metastatic PCa has been completely revised.
  • Section 6.10 – Treatment of PSA-only recurrence after treatment with curative intent,
    o             Section 6.10.5.2 – Hormonal therapy; the key findings of a systematic review on ‘The role of hormonal                                             treatment in PCa patients with non-metastatic disease recurrence after local curative treatment’ [4] have
    been included.
  • Section 6.10.11 – Salvage lymph node dissection has been included as a new topic.
  • Section 6.11 -Treatment: Castration-resistant PCa (CRPC) has been completely revised.

Changed recommendations and evidence summaries can be found in sections:

5.1.1 Guidelines for screening and early detection 

Recommendation LE GR
Do not subject men to PSA testing without counselling on the potential risks and benefits. 3 B

PSA = prostate-specific antigen.

 5.3.5 Guidelines for staging of PCa 

Intermediate-risk PCa LE GR
In predominantly Gleason pattern 4, metastatic screening, include at least a cross-sectional abdominopelvic imaging, and a CT/MRI and bone-scan for staging purposes. 2a  A*
In predominantly Gleason pattern 4, use prostate mpMRI for local staging and metastatic screening. 2b A

 

High-risk localised PCa/ High-risk locally advanced PCa LE GR
Perform metastatic screening including at least cross-sectional abdominopelvic imaging and a bone-scan. 2a A

*Upgraded following panel consensus.

mpMRI = multiparametric magnetic resonance imaging; CT = computed tomography.

 6.4.5 Summary of evidence and guidelines for experimental therapeutic options to treat clinically localised PCa 

Summary of evidence LE
The available short-term data does not prove equivalence. 2b
There is no reliable long-term comparative data to indicate that CSAP or HIFU leads to equivalent oncological outcomes compared with radical prostatectomy or EBRT. 3 
PSA nadir values after ablative therapies may have prognostic value. 3
Focal therapy of any sort appears promising but remains investigational, with uncertainties surrounding follow-up and re-treatment criteria. 3 

 

Recommendation LE GR
Only offer cryotherapy and HIFU within a clinical trial setting. 3 B

HIFU = high-intensity focused ultrasound. 

6.6.7 Guidelines for hormonal treatment of metastatic prostate cancer 

Recommendation LE GR
In newly diagnosed M1 patients, offer castration combined with docetaxel, provided patients are fit enough to receive chemotherapy. 1a  A

 6.10.4.6 Guidelines for imaging in patients with biochemical failure 

PSA recurrence after RT LE GR
Choline PET/CT imaging is recommended to rule out lymph nodes or distant metastases in patients fit enough for curative salvage treatment 2b  B

PET/CT = positon emission tomography/computed tomography. 

6.10.11.1 Guidelines for salvage lymph node dissection 

Recommendation
Discuss salvage LND with men experiencing nodal recurrence after local treatment but it should be considered experimental and biochemical recurrence after salvage LND occurs in the majority of cases.

LND = lymph node dissection. 

6.11.10 Summary of evidence and recommendation for life-prolonging treatments of mCRPC 

Summary of evidence LE
No clear-cut recommendation can be made for the most effective drug for secondary treatment (i.e. hormone therapy or chemotherapy) as no clear predictive factors exist. 3 

 Specific sections of the text have been updated based on a systematic review questions prioritised by the Guidelines Panel. These reviews were performed using standard Cochrane systematic review methodology;
http://www.cochranelibrary.com/about/about-cochrane-systematic-reviews.html

  • Section 5.2.4.2 – Multiparametric MRI (mpMRI)
    What is the performance of prostate pre-biopsy multi parametric MRI in predicting prostate biopsy results? [3].
  • Section 6.10.5.2 – Hormonal therapy
    The role of hormonal treatment in PCa patients with non-metastatic disease recurrence after local curative treatment: A systematic review [4].

2015

The literature in the complete document has been assessed and updated, whenever relevant.

Conclusions and recommendations have been rephrased and added to throughout the current document. The sections where changes were made (additional information or a change in the grade of recommendation occurred) can be found below:

 Table 4.1.2: EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer

Low-risk Intermediate-risk High-risk
Definition PSA < 10 ng / mL
and GS < 7
and cT1-2a
PSA 10-20 ng /mL
or GS 7
or cT2b
PSA > 20 ng / mL
or GS > 7
or cT2c
any PSA
any GS
cT3-4 or cN+
Localised Locally advanced

5.2.4.3 Guidelines for imaging

  LE GR
When clinical suspicion of PCa persists in spite of negative biopsies, MRI-targeted biopsies are recommended. 2b B

MRI = magnetic resonance imaging.

Table 5.2.4: Recommended terminology for reporting prostate biopsies [3]

  • Benign/negative for malignancy. If appropriate, include a description.
  • Active inflammation
  • Granulomatous inflammation
  • High-grade PIN
  • High-grade PIN with atypical glands, suspicious for adenocarcinoma (PINATYP)
  • Focus of atypical glands/lesion suspicious for adenocarcinoma/atypical small acinar proliferation, suspicious for cancer
  • Adenocarcinoma

PIN = prostatic intraepithelial neoplasia.

5.2.7       Guidelines for the clinical diagnosis of prostate cancer

  LE GR
Transurethral resection of the prostate should not be used as a tool for cancer detection 2a A

5.3.4       Guidelines for staging of prostate cancer

Any risk group staging LE GR
Additional imaging is required only if it changes patient management. 2a A*
For local staging, CT and TRUS should not be used. 3 A
For up-front staging, PET-scanning should not be used. 2a A

 

Low-risk localised PCa LE GR
No additional imaging is recommended for staging purposes. 2a A

 

Intermediate-risk PCa LE GR
In predominantly Gleason pattern 4, bone scan and cross-sectional imaging is required. 2a A*

 

High- risk localised PCa/ High-risk locally advanced PCa LE GR
Prostate mpMRI should be used for local staging. 2b A
CT/MRI and bone-scan should be used in staging. 2b A
For up-front staging, PET-scanning should not be used. 2a A

CT = computed tomography; MRI = magnetic resonance imaging; PET = positron emission tomography; TRUS = transurethral resection.

7.1.5       Guidelines for active surveillance and watchful waiting 

Recommendations – active surveillance LE GR
Patients who would be suitable for surgery and radiotherapy must have these options discussed with them. 4 A*

7.2.11    Guidelines for radical prostatectomy

 Guidelines LE GR
Patients who are suitable for AS and radiotherapy must have these options discussed with them. 4 A*
In patients with low- and intermediate-risk  PCa  and a life expectancy > 10 years, RP should be offered. 1b A
Nerve-sparing surgery may be attempted in pre-operatively potent patients with low risk for extracapsular disease (T1c, GS < 7 and PSA < 10 ng/mL, or refer to Partin tables/nomograms). 2b B
Multiparametric MRI may help in deciding when to perform nerve-sparing procedures in intermediate- and high-risk disease. 2b B
In patients with high-risk localised PCa and a life expectancy of > 10 yr, RP should be offered in a multimodality setting. 2a A
In selected patients with locally advanced (cT3a) PCa, and a life expectancy > 10 yr, RP may be offered in a multimodality setting. 2b B
In highly selected patients with locally advanced PCa (cT3b-T4 N0 or any T N1), RP may be offered in a multimodality setting. 3 C
NHT before RP is not recommended. 1a A
Adjuvant HT for pN0 is not recommended. 1a A
Adjuvant ADT is the standard of care for node-positive (pN+). 1b A

ADT = androgen deprivation therapy; AS = active surveillance; HT = hormonal therapy; MRI = magnetic resonance imaging; NHT = neoadjuvant hormonal therapy; RP = radical prostatectomy.

7.3.10    Conclusion and Guidelines for definitive radiotherapy

Statement LE
The highest effect of adjuvant radiotherapy is seen in patients with pT3R1 PCa.  1a

 

Guidelines LE GR
Patients who would be suitable for AS and surgery must have these options discussed with them. 4 A
EBRT should be offered in all risk groups of non-metastatic PCa. 2a A
In low-risk PCa the total dose should be 74 to 78 Gy. 1a A
In patients with low-risk PCa, without a previous TURP and with a good IPSS and a prostate volume < 50 mL, LDR brachytherapy is a treatment option. 2a A
In intermediate-risk PCa the total dose should be 76-78 Gy, in combination with short-term ADT (4-6 mo). 1b A
In patients with high-risk localised PCa, the total dose is 76-78 Gy in combination with long-term ADT (2-3 yr) is recommended. 1b A
In patients with locally advanced cN0 PCa, radiotherapy must be given in combination with long-term ADT (2-3 yr). 1a A
IMRT is the recommended modality for definitive treatment of PCa by EBRT. 2a A
In patients with cN+ PCa pelvic external irradiation can be given in combination with immediate long-term ADT. 2b B
In patients with pT3,N0M0 PCa and an undetectable PSA following RP, adjuvant external beam irradiation should be discussed as an option because it improves at least biochemical-free survival. 1a A
Patients with pT3,N0M0 PCa and an undetectable PSA following RP should be informed about salvage irradiation as an alternative to adjuvant irradiation when PSA increases (See Section 6.10.5.1). 2b A

ADT = androgen deprivation therapy; AS = active surveillance; EBRT = external beam radiation therapy; IMRT = PSA = prostate-specific antigen; RP = radical prostatectomy.

Primary treatment of prostate cancer Gr
General comments Patients suitable for several treatment modalities (active surveillance, surgery, radiotherapy) must have these options discussed with them. A*
In patients who are surgical candidates for radical prostatectomy, all approaches (i.e.  open, laparoscopic or robotic) are acceptable as no single approach has shown clear superiority in terms of functional or oncological results. A
EBRT should be offered in all risk groups of non-metastatic PCa. A
IMRT is the recommended modality for definitive treatment of PCa by EBRT. A
Treatment Comment  
Low risk PCa Watchful waiting Watchful waiting may be offered to patients not eligible for local curative treatment and those with a short life expectancy. A
During watchful waiting, the decision to start non-curative treatment should be based on symptoms and disease progression. B
Active surveillance Active surveillance is an option in patients with the lowest risk of cancer progression: > 10 years life expectancy, cT1/2, PSA ≤ 10 ng/mL, biopsy Gleason score ≤ 6, ≤ 2 positive biopsies, minimal biopsy core involvement (≤ 50% cancer per biopsy). A
Follow-up should be based on DRE, PSA and repeat biopsies. The optimal follow-up interval is still unclear. A
Radical prostatectomy In patients with a life expectancy > 10 years, RP should be offered. A
Nerve-sparing surgery may be attempted in pre-operatively potent patients with low risk for extracapsular disease (T1c, GS < 7 and PSA < 10 ng/mL, or refer to Partin tables/nomograms). B
LND is not indicated in low-risk PCa. A
Radiotherapy In low-risk PCa the total dose should be 74 to 78 Gy. A
In patients with low-risk PCa, without a previous TURP and with a good IPSS and a prostate volume < 50 mL, LDR brachytherapy is a treatment option. A
Cryotherapy, HIFU In patients who are unfit for surgery or radiotherapy, cryotherapy or HIFU might be an alternative treatment for PCa. The lack of long-term efficacy compared to standard modality should be discussed with patients. C
Focal treatment Focal therapy of PCa is still in its infancy and cannot be recommended as a therapeutic alternative outside clinical trials. A
Androgen suppression Unsuitable. A
Intermediate risk PCa Watchful waiting Watchful waiting may be offered to patients not eligible for local curative treatment and those with a short life expectancy. A
Active surveillance Not an option. A
Radical prostatectomy In patients with a life expectancy > 10 years, RP should be offered. A
Nerve-sparing surgery may be attempted in pre-operatively potent patients with low risk for extracapsular disease (T1c, GS < 7 and PSA < 10 ng/mL, or refer to Partin tables/nomograms). B
Multiparametric MRI may help in deciding when to perform nerve-sparing procedures in intermediate- and high-risk disease. B
eLND should be performed if the estimated risk for positive lymph nodes exceeds 5%. B
Limited LND should not be performed. A
In patients with pT3,N0M0 PCa and an undetectable PSA following RP, adjuvant external beam irradiation has to be discussed as an option because it improves at least biochemical-free survival. A
Patients with pT3,N0M0 PCa and an undetectable PSA following RP should be informed about salvage irradiation as an alternative to adjuvant irradiation when PSA increases. A
Adjuvant HT for pN0 is not recommended
Radiotherapy In intermediate- risk PCa the total dose should be 76-78 Gy, in combination with short-term ADT (4-6 mo). A
Androgen suppression monotherapy No place in asymptomatic patients. A
High risk PCa Watchful waiting High risk localised: Watchful waiting may be offered to patients not eligible for local curative treatment and those with a short life expectancy.
High risk locally advanced: In M0 patients unwilling or unable to receive any form of local treatment, a deferred treatment policy using ADT as monotherapy is feasible in asymptomatic patients with a PSADT > 12 months and a PSA < 50 ng/mL and non-poorly differentiated tumour. A
  Active surveillance Not appropriate. A
Radical prostatectomy NHT before RP is not recommended. A
eLND should be performed in high-risk PCa. A
Limited LND should not be performed. A
High risk localised: In patients with high-risk localised PCa and a life expectancy of > 10 yr, RP should be offered in a multimodality setting. B
Nerve-sparing surgery may be attempted in pre-operatively potent patients with low risk for extracapsular disease (refer to Partin tables/nomograms). B
Multiparametric MRI may help in deciding when to perform nerve-sparing procedures in intermediate- and high-risk disease. B
High risk locally advanced: In highly selected patients with locally advanced PCa (cT3b-T4 N0 or any T N1), RP may be offered in a multimodality setting. C
In patients with pT3,N0M0 PCa and an undetectable PSA following RP, adjuvant external beam irradiation has to be discussed as an option because it improves at least biochemical-free survival. A
Patients with pT3,N0M0 PCa and an undetectable PSA following RP should be informed about salvage irradiation as an alternative to adjuvant irradiation when PSA increases. A
Radiotherapy In patients with high-risk localised PCa, the total dose is 76-78 Gy in combination with long-term ADT (2-3 yr is recommended). A
In patients with locally advanced cN0 PCa, radiotherapy must be given in combination with long-term ADT (2-3 yr is recommended). A
Androgen suppression monotherapy Reserved for those unwilling or unable to receive any form of local treatment and either symptomatic or asymptomatic with a PSADT < 12 months and a PSA > 50 ng/mL and a poorly differentiated tumour. A
N1 patients
cN1 In patients with cN+ PCa pelvic external irradiation can be given in combination with immediate long-term ADT. B
pN1 after eLND Adjuvant ADT is the standard of care for node-positive (pN+). A
Adjuvant ADT with additional radiotherapy may have a role. B
Expectant management is optional when the patient has undergone eLND and ≤ 2 nodes show microscopic involvement and a PSA < 0.1 ng/mL and absence of extranodal extension. B
Metastatic PCa Watchful waiting In M1 asymptomatic patients, deferred castration should be discussed with a well-informed patient. B
Active surveillance Unsuitable. A
Radical prostatectomy Unsuitable outside clinical trial. A
Radiotherapy to the prostate Unsuitable outside clinical trial. A
Androgen suppression Surgical- or medical castration (LHRH agonist or antagonist). A
No recommendation can be made to define the best population for combining castration with upfront Docetaxel. A
Castration combined with local treatment / other new hormonal treatments (abiraterone acetate or ezalutamide) should not be used outside clinical trials. A
In M1 asymptomatic patients, immediate castration should be offered to defer progression to a symptomatic stage and prevent serious disease progression-related complications. A
In M1 symptomatic patients, immediate castration should be offered to palliate symptoms and reduce the risk for potentially catastrophic sequelae of advanced disease (spinal cord compression, pathological fractures, ureteral obstruction, extraskeletal metastasis). A
In M1 patients, short-term administration of anti-androgens is recommended to reduce the risk of the ‘flare-up’ phenomenon in patients with advanced metastatic disease who are to receive an LHRH agonist. A
In M1 patients short term administration of anti-androgens should be given for some weeks only (starting treatment on the same day as an LHRH analogue is started or for up to 7 days before the first LHRH analogue injection. A
In M1 patients, administration of anti-androgens as monotherapy should not be considered. A
In asymptomatic M1 patients, intermittent treatment can be offered to highly motivated men, with a major PSA response after the induction period. B
Based on the schedules in use in clinical trials, Treatment is stopped when the PSA is < 4 ng/mL after 6 to 7 months of treatment. Treatment is resumed when the PSA is >10-20 ng/mL. C
Combined treatment with LHRH agonists and NSAA is recommended. A
Antagonists might be an option. B
Castrate resistant status Patients should not be started on second-line therapy unless their testosterone serum levels are < 50 ng/dL. A
There is no evidence for treatment of non-metastatic CRPC outside a clinical trial. A
Patients with mCRPC should be counseled, managed and treated by a multidisciplinary team. A
Men treated with maximal androgen blockade should stop the anti-androgen therapy once PSA progression is documented.
Comment: Four to six weeks after discontinuation of flutamide or bicalutamide, an eventual anti-androgen withdrawal effect will be apparent.
A
No clear-cut recommendation can be made for the most effective drug for secondary treatment (i.e. hormone therapy or chemotherapy) as no clear predictive factors exist. A
Salvage hormonal treatment using abiraterone acetate is a valid option. A
Salvage hormonal treatment using enzalutamide is a valid option. A
In patients with metastatic CRPC who are candidates for salvage cytotoxic therapy, docetaxel at 75 mg/m2 every 3 weeks has shown a significant survival benefit. A
In patients with relapse following salvage docetaxel chemotherapy cabazitaxel, abiraterone acetate and enzalutamide are regarded as first-choice options for second-line treatment in mCRPC. A
In men with mCRPC with symptomatic bone metastases, who are ineligible for or progressing after docetaxel, treatment with Ra 223 (alpharadin) has shown a survival benefit. A
Bone protective agents may be offered to patients with skeletal metastases (denosumab being superior to zoledronic acid) to prevent osseous complications. However, the benefits must be balanced against the toxicity of these agents, and jaw necrosis in particular must be avoided. A
Calcium and vitamin D supplementation must be systematically considered when using either denosumab or bisphosphonates. A
In patients with neurological symptoms, spinal surgery or decompressive radiotherapy might be indicated as emergency interventions. High-dose corticosteroids must be always initially considered. A

A*  Upgraded following panel consensus.

 ADT = androgen deprivation therapy; DRE = digital rectal examination; EBRT = external beam radiation therapy; HIFU = high-intensity focused ultrasound; LHRH = luteinising-hormone-releasing hormone; eLND = (extended) lymph node dissection; mCRPC = metastatic castrate-resistant prostate cancer; MRI = magnetic resonance imaging; NHT = neoadjuvant hormonal therapy; NSAA = non-steroidal anti-androgen; PSADT = PSA doubling time; RP = radical prostatectomy; TURP = transurethral resection of the prostate.

2014

For this 2014 update, the following changes should be noted:

Chapter 2
Background: The literature has been revised.

Chapter 3
Classification: The literature has been updated and the text has been expanded (definitions and d’Amico classification).

Chapter 4
Risk factors and chemoprevention: The literature has been revised and additional information included on 5-alpha-reductase inhibitors (5-ARIs).

Chapter 5
Screening and early detection: The literature has been revised.

Chapter 6
Diagnosis: The literature has been revised and information on the role of imaging as a diagnostic tool has been added. A number of recommendations have been included.

Chapter 7
Staging: This chapter has been restructured, and additional information on the use the use of MRI as a diagnostic tool has been added.

Chapter 8
Treatment: deferred treatment (active surveillance/watchful waiting): The literature has been revised and the text has been restructured.

Chapter 9
Treatment Radical Prostatectomy: New information has been included, in particular in sections 9.4.1 – 9.4.3.

Chapter 10
Treatment: definitive radiotherapy: The literature has been revised and an overview table listing the three randomized trials for adjuvant radiation therapy after radical prostatectomy has been added.

Chapter 11
Options other than surgery and radiotherapy for the primary treatment of localised PCa: The literature has been revisited and the text was restructured. A number of new recommendations were added.

Chapter 12
Hormonal therapy; rationale and available drugs: The literature has been revised.

Chapter 13
Metastatic PCa – Hormonal therapy: The literature has been revised.

Chapter 14
Management of PCa in senior adults: This section was completely revised.

Chapter 15
Quality of life of patients with localised PCa: The literature has been revised and the text has been condensed. A number of new recommendations were added.

Chapter 17
Follow-up after treatment with curative intent: The literature has been revised and the text was condensed.

Chapter 18
Follow-up after hormonal treatment: The literature has been revised and the text was condensed.

Chapter 19
Treatment of biochemical failure after curative intent: The literature has been revised and the text has been restructured. A number of new recommendations were added.

Chapter 20
Castration-resistant PCa (CRPC): The literature has been updated and the text has been completely restructured. Table 20.3 presents an overview of the review done to assess the medical management of men with CRPC. A treatment flowchart is provided and a number of new recommendations were added.

2013

For this 2013 update, the following changes should be noted:

Chapter 8
Treatment: deferred treatment (watchful waiting)”
In section 8.2.1 (Watchful waiting), the findings of the PIVOT trial have been included.
Chapter 9
Treatment Radical Prostatectomy: The literature has been updated and additional recommendations for lymph node dissection have been included in section 9.7 (Summary of radical prostatectomy and eLND in high-risk localized disease).
Chapter 10
Treatment definitive radiotherapy: The literature has been updated, as well as the findings in section 10.10 (Guidelines for definitive radiotherapy). The text has been completely restructured, in particular in sections 10.3.2 (Neoadjuvant or adjuvant hormone therapy plus radiotherapy), 10.3.2.3 (high-risk group), 10.3.4 (The benefits of lymph-node irradiation in the prostate), 10.3.4.2 (Very high-risk PCa) and 10.7.1 (Immediate [adjuvant] postoperative external irradiation after radical prostatectomy).
Chapter 12
Hormonal therapy; rationale and available drugs: The literature has been updated. The chapter has been completely restructured and a section of the text was moved into a separate chapter (Chapter 15 “Metastatic prostate cancer – Hormonal therapy”), to facilitate consultation.
Chapter 13
Metastatic Prostate Cancer – Hormonal therapy: The literature has been updated and the text was restructured. In particular information has been added, in sections 13.1 (Prognostic factors), and 13.4 (Indications for hormonal therapy). Also section 13.4 (indications for hormonal therapy) was revised.
Chapter 15
Quality of life of patients with localised prostate cancer: The literature has been updated.
Chapter 18
Treatment of biochemical failure after treatment with curative intent: The literature has been updated and the text has been restructured.
Chapter 19
Treatment of biochemical failure after curative intent: The literature has been updated. Additional information on imaging modalities has been added, most notably in the summary at the end of section 19.4.1 (Diagnostic procedures for PSA relapse following radical prostatectomy). New data has been included in sections 19.4.2 (Diagnostic studies for PSA relapse following radiation therapy, 19.5.1 (Radiotherapy for PSA-only recurrence after radical prostatectomy) and on new techniques in section 19.6.1 (Salvage radical prostatectomy).
Chapter 20
Castration-resistant prostate cancer (CRPC): The literature has been updated resulting in minor changes to the recommendations. The text has been completely restructured and a new algorithm for PSA progression following initial hormonal therapy was added in section 20.5 (Secondary hormonal therapy). New information was included in sections 20.8 (Novel hormonal drugs targeting the endocrine pathways), 20.9 (Non-hormonal therapy), as well as in section 20.11, resulting in expanding the recommendations for salvage treatment after Docetaxel. The summary of treatment recommendations (section 20.13) was subjected to a minor revision.

2012

For this 2012 update, the following changes should be noted:

Chapter 6
Diagnosis: All literature has been revisited, new data has been added. Most notably in sections 6.2.3 (PCA3 marker), 6.4.8 (Antibiotics prior to biopsy), 6.4.11 (Complications), 6.5 (Pathology of prostate needle biopsies) and 6.6.2.3 (Definition of extraprostatic extension). In section 6.4.8 (Antibiotics prior to biopsy), the quinolones resistance related to infectious complications after biopsy.

Chapter 8
Watchful waiting/active surveillance: Additional data on the impact of radical prostatectomy compared to watchful waiting (WW) has been added. Data have been added supporting that comorbidity status is the leading cause of death at ten years, especially for Charlson score = 2, irrespective of age, even for those with an aggressive tumour. Active surveillance as appropriate for highly selected, low risk patients only. Early re-biopsy plays as an increasingly important role in the patient’s selection process. In general, repeat biopsies are a major tool for patient follow-up.

Chapter 9
Treatment: Radical prostatectomy: Additional data have been included in section 9.1 (Introduction) on robot-assisted laparoscopic prostatectomy (RALP). Added emphasis is given to the need for a multidisciplinary approach in the treatment of high-risk localised disease Section 9.4 (High-risk localised PCa).

Chapter 10
Treatment: Definitive radiation therapy: Additional data has been added on the various hormonal therapy options, section 10.8 (Locally advanced PCa: T3-4, N0M0).

Chapter 11
Experimental local treatment of prostate cancer: Additional data has been added on oncological outcomes and treatment-associated complications (Section 11.3 -HIFU of the prostate). Additional data on salvage radical prostatectomy versus CSAP has been included (Section 16.6.2 – Salvage cryosurgical ablation of the prostate for radiation failures). A new section has been added on salvage high-intensity focused ultrasound (HIFU).

Chapter 12
Hormonal treatment: Data from the largest randomised controlled trial on PCa patients relapsing after radiotherapy has been incorporated, showing that intermittent androgen-deprivation therapy (ADT) proved to be as effective as continuous ADT. Additional data regarding bone protection and the potential role of denosumab in delaying secondary bone metastases. However, denosumab does not impact overall survival or cancer-specific survival. Further data on androgen deprivation therapy (ADT) was included. ADT is associated with increased cardiac morbidity, not an increase in cardiac mortality. The presence of a congestive heart failure or myocardial infarction increases the mortality risk.

Chapter 15
Follow up after hormonal treatment: The literature has been revisited. The importance of bone- and testosterone monitoring is reinforced.

Chapter 16
Treatment of biochemical failure after treatment with curative intent: In section 16.4 (Evaluation of PSA progression), additional data has been added on the role of choline PET/CT in the diagnosis of men with rising PSA following radical prostatectomy.

Chapter 17
Castration resistant prostate cancer: For section 17.4 (Recommendations for assessing therapeutic response), new literature has been incorporated and recommendations have changed. 17.8.5.2 (Abiraterone acetate), new information has been added. 17.9.10 (Specific bone targets), information from the ENTHUSE study has been included.

New topics

  • Quality of life of patients with localised prostate cancer
  • Chapter 16, A section has been added on salvage high-intensity focused ultrasound (HIFU)
  • Chapter 17, Section 17.10.4 RANK ligand inhibitors

2011

For this 2011 update, the following changes should be noted:

  • Unification of all data and tables with the new pocket version. In particular Tables 5 and 6
  • Section 7.4 (Guidelines for the diagnosis and staging of PCa)
  • Chapter 13 (Guidelines for primary treatment)
  • Section 16.7 (Second-line therapy after treatment with curative intent)
  • Chapter 17 (Castration-refractory PCa) sections 17.11-17.12 & 17.3

The existing text was revisited.