Imaging guidelines in newly diagnosed prostate cancer

Guideline

Categories

Imaging recommendation

EAU

Low-risk*

- No imaging

Intermediate-risk*; predominantly GI 4

- Multiparametric MRI for local staging 1!

- CT-abdomen/pelvis - Bone scan 2, 3, 4, 5!

High-risk*

- Multiparametric MRI for local staging - CT-abdomen/pelvis - Bone scan2, 3, 4, 5!

General / any risk

- No CT / TRUS for local staging - No Choline-PET for detection of LN-metastases - No final recommendation on Ga/F-PSMA PET - No final recommendation on WB-MRI

NCCN (Version : 2.2017)

If life expectancy >5y or asymptomatic AND: - T1 and PSA >20ng/ml - T2 and PSA >10ng/ml - Gleason 9 - T3 or T4

- Bone scan2, 3, 4, 5!

Symptomatic AND: - T3; T4; - T1-T2 and nomogram >10% risk of LN-metastases Cagiannos I., et al 7!

- CT/MRI

AUA/ASTRO SUO 2017

Very low and Low risk*

- No CT-abdomen/pelvis or Bone scan

Unfavourable Intermediate/ High-Risk*

- CT/MRI - Bone scan

IKNL
(Guideline prostate cancer, version 2.1)

- PSA >20ng/ml - cT3 - Gleason 8 - Symptomatic

- Bone scan or choline PET6!

General / any risk

- Multiparametric MRI for primary diagnosis (if available) 1!
- Multiparametric MRI for staging (only if relevant for therapy)

- No CT for staging
- No routine Choline-PET for primary Staging

* Low-risk: PSA < 10 ng/mL; GS < 7 (ISUP grade 1); cT1-2a
Intermediate-risk: PSA 10-20 ng/mL; GS 7 (ISUP grade 2/3) or cT2b
High-risk: PSA > 20 ng/mL; or GS > 7 (ISUP grade 4/5); or locally advanced

x Very Low Risk: PSA <10 ng/ml AND Grade Group 1 AND clinical stage T1-T2a AND <34% of biopsy cores positive AND no core with >50% involved, AND PSA density <0.15 ng/ml/cc
Low Risk: PSA <10 ng/ml AND Grade Group 1 AND clinical stage T1-T2a
Intermediate Risk: PSA 10-<20 ng/ml OR Grade Group 2-3 OR clinical stage T2b-c
Favorable: Grade Group 1 (with PSA 10-<20) OR Grade Group 2 (with PSA<10)
Unfavorable: Grade Group 2 (with either PSA 10-<20 or clinical stage T2b-c) OR Grade Group 3 (with PSA < 20) High Risk: PSA >20 ng/ml OR Grade Group 4-5 OR clinical stage >T3 OR locally advanced

  1. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham AP, Oldroyd R, Parker C, Emberton M; PROMIS study group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25;389(10071):815-822.
  2. Briganti A, Passoni N, Ferrari M, et al. When to Perform Bone Scan in Patients with Newly Diagnosed Prostate Cancer: External Validation of the Currently Available Guidelines and Proposal of a Novel Risk Stratification Tool. Eur Urol 2010; 57: 551–8.
  3. Shen G, Deng H, Hu S, Jia Z. Comparison of choline-PET/CT, MRI, SPECT, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a meta-analysis. Skeletal Radiol. 2014; 43: 1503–13.
  4. Zacho HD, Manresa JAB, Aleksyniene R, et al. Three-minute SPECT/CT is sufficient for the assessment of bone metastasis as add-on to planar bone scintigraphy: prospective head-to-head comparison to 11-min SPECT/CT. EJNMMI Res 2017; 7: 1.
  5. Palmedo H, Marx C, Ebert A, et al. Whole-body SPECT/CT for bone scintigraphy: Diagnostic value and effect on patient management in oncological patients. Eur J Nucl Med Mol Imaging 2014; 41: 59–67.
  6. Beheshti M, Imamovic L, Broinger G, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology 2010; 254: 925–33.62.
  7. Cagiannos I, Karaciwicz P, Eastham JA, et al. A Preoperative Nomogram Identifying Decreased Risk of Positive Pelvic Lymph Nodes in Patients With Prostate Cancer. J Urol 2003; 170: 1798–803.

Imaging guidelines at biochemical recurrence of prostate cancer

Guideline

Categories

Imaging recommendation

EAU

After prostatectomy:

 

 

- PSA <1ng/ml

- No imaging

 

- PSA >1ng/ml

- Choline or PSMA-ligand PET8!

 

After radiotherapy:
(If fit enough for curative salvage)

- Multiparametric MRI - Choline-PET9, 10, 11! - Ga-PSMA PET no standard tool, yet should be considered if available12, 13, 14, 15, 16, 17, 18!

 

General / any risk: - Only if PSA >10ng/ml - PSAdt <6mnth - PSA velocity>0,5ng/ml/mo

- CT-abdomen/pelvis19, 20! - Bone scan19, 20! - No final recommendation on WB-MRI21, 22!

NCCN (Version : 2.2017)

After prostatectomy:

- Bone scan

 

After Radiotherapy
If candidate for local therapy
(T1-2, Nx or N0; Life expectancy >10y; PSA>10ng/ml)

- X-ray chest
- Bone scan
- Prostate MRI
Consider:
- CT/MRI-abdomen/pelvis
- C-11 Choline PET
23!

IKNL
(Guideline prostate cancer, version 2.1)

- PSA >5ng/ml - PSA >1ng/ml and PSAdt <3mo - Gleason 8

- Choline PET - Bone scan only if PSA >20ng/ml

 

General / any risk

- No CT for staging
Consider: - Multiparametric MRI for local recurrence

  1. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71: 618–29.
  2. Umbehr MH, Muntener M, Hany T, Sulser T, Bachmann LM. The Role of 11C-Choline and 18F-Fluorocholine Positron Emission Tomography (PET) and PET/CT in Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol 2013; 64: 106–17.
  3. Evangelista L, Zattoni F, Guttilla A, et al. Choline PET or PET/CT and biochemical relapse of prostate cancer: A systematic review and meta-analysis. Clin. Nucl. Med. 2013; 38: 305–14.
  4. Treglia G, Ceriani L, Sadeghi R, Giovacchini G, Giovanella L. Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: A meta-analysis. Clin Chem Lab Med 2014; 52: 725–33.
  5. Afshar-Oromieh A, Malcher A, Eder M, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013; 40: 486–95.
  6. Perera M, Papa N, Christidis D, et al. Sensitivity, Specificity, and Predictors of Positive 68Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur. Urol. 2016; 70: 926–37.
  7. Afshar-Oromieh A, Hetzheim H, Kratochwil C, et al. The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions. J Nucl Med 2015; 56: 1697–705.
  8. Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid 68Ga-PSMA-ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 2015; 56: 668–74.
  9. Ceci F, Uprimny C, Nilica B, et al. 68Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging 2015; 42: 1284–94.
  10. Montorsi F, Gandaglia G, Fossati N, et al. Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer. Eur Urol 2017; 72: 432–8.
  11. Maurer T, Weirich G, Schottelius M, et al. Prostate-specific Membrane Antigen-radioguided Surgery for Metastatic Lymph Nodes in Prostate Cancer. Eur Urol 2015; 68: 530–4.
  12. Kane CJ, Amling CL, Johnstone PAS, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology 2003; 61: 607–11.
  13. Lindenberg ML, Turkbey B, Mena E, Choyke PL. Imaging locally advanced, recurrent, and metastatic prostate cancer: A review. JAMA Oncol. 2017; 3: 1415–22.
  14. Eschmann SM, Pfannenberg AC, Rieger A, et al. Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer. NuklearMedizin. 2007; 46: 161–8.
  15. Zacho HD, Nielsen JB, Afshar-Oromieh A, Haberkorn U, deSouza N, De Paepe K, Dettmann K, Langkilde NC, Haarmark C, Fisker RV, Arp DT, Carl J, Jensen JB, Petersen LJ. Prospective comparison of (68)Ga-PSMA PET/CT, (18)F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2018; 45:1884-1897. 
  16. Evangelista L, Zattoni F, Guttilla A, et al. Choline PET or PET/CT and biochemical relapse of prostate cancer: A systematic review and meta-analysis. Clin. Nucl. Med. 2013; 38: 305–14.

Imaging guidelines at the castrate resistant stage of prostate cancer

Guideline

CRPC (APC)

Imaging recommendation

comments

EAU

- PSA >2ng/ml
- Symptomatic

- Bone scan 24, 25, 26, 27, 28, 29! - CT

(If negative repeat when PSA >5ng/ml and after PSAdt)

- mCRPC - monitoring of treatment

- CT-chest - CT-abdomen/pelvis - Bone scan

(Repeated every 6 months)

NCCN(Version: 2.2017)

Castration-naïve

- Bone scan - X ray-chest - CT/MRI-abdomen/pelvis with and without contrast Consider:- Choline PET30, 31!

Monitoring mCRPC

- CT/MRI - Bone scan

(Every 6-12 months) (Every 8-12 weeks)

APCCC 2017 (Delphi method >75% agreement)

Oligometastatic castration-naïve Pca

-NoCT-abdomen/pelvis or Bone scan

Staging and monitoring mCRPC when treating with Ra-223

- CT-Thorax/Abdomen - Bone scan

APCC 2015

mCRPC

- CT-chest - CT-abdomen/pelvis - Bone scan - No routine WB-MRI or PET/CT for staging

(Before start of treatment)

PCWG3

If locally persistent/recurrent

- Multiparametric MRI

All patients

- CT-chest(<5 mm slices) - CT-abdomen/pelvis (<5 mm slices) - Bone scan - WB-MRI and PET/CT (all tracers) not recommended

  1. Miyoshi Y, Yoneyama S, Kawahara T, et al. Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases. BMC Cancer 2016; : 1–7.
  2. Poulsen MH, Rasmussen J, Edenbrandt L, et al. Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer. BJU Int 2016; 117: 748–53.
  3. Reza M, Bjartell A, Ohlsson M, et al. Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy. EJNMMI Res 2014; 4: 58.
  4. Armstrong AJ, Kaboteh R, Carducci MA, et al. Assessment of the bone scan index in a randomized placebo-controlled trial of tasquinimod in men with metastatic castration-resistant prostate cancer (mCRPC). Urol Oncol 2014; 32: 1308–16.
  5. Kaboteh R, Gjertsson P, Leek H, et al. Progression of bone metastases in patients with prostate cancer - automated detection of new lesions and calculation of bone scan index. EJNMMI Res 2013; 3: 64.
  6. Ulmert D, Kaboteh R, Fox JJ, et al. A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the bone scan index. Eur Urol 2012; 62: 78–84.
  7. Ceci F, Castellucci P, Nanni C, Fanti S. PET/CT imaging for evaluating response to therapy in castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 2103–4.
  8. Schwarzenböck SM, Eiber M, Kundt G, et al. Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 2105–13.

Imaging characteristics and evidence level

Imaging modality 

Newly diagnosis staging

BCR

CRPC

ROC characteristics

Evidence level

ROC characteristics

Evidence level

ROC characteristics

Evidence level

SIM

CT

Node:

Sens +

Spec ++

2a/B

Limited value and not recommended unless a high PSA value

3b/B

NA

2a/B

Bone scintigraphy

Bone:

Sens +++

Spec +++

3a/B

Limited value and not recommended unless PSA >10 ng/mL 

3b/B

‘2+2 rule’ recommended by PCWG

3b/B

MIM

18F-NaF

Bone:

Sens ++++

Spec +++

PPV+++

NPV ++++

2a/B

NA

NA

NA

NA

18!F-Choline

Bone:

Sens +++

Spec ++++

Node: 

Sens ++

Spec ++++

PPV+++

NPV ++++

2a/B



1b/A

Patient basis

Sens +++

Spec +++

Influenced by PSA level at recurrence

2a/B

Bone & soft tissue:

Sens++++

Spec ++++

PPV++++

NPV ++++

2b/B

WB-MRI with DWI

Bone:

Sens++++

Spec++++

AUC ++++

2a/B

Positive at low PSA levels 

2b/B

Anatomic and functional criteria

2b/B

PSMA

Bone:

Sens +++

Spec ++++

Node: 

Sens++

Spec++++

PPV+++

NPV +++

2b/B

Patient basis:

Sens +++

Spec +++

Influenced by PSA level at recurrence

2a/B

Not reliable for AR axis targeting treatments

NA

“+” “++” 50%-69%;
“+++” 70%-89%;
“++++” 90%

AR= androgen receptor;
BCR= biochemical relapse;
CRPC= castration-resistant prostate cancer;
DWI=diffusion weighted imaging;
NA=no adequate data in this population or similar ROC and evidence level to staging;
NPV=negative predictive value;
PPV=positive predictive value;
PCWG=prostate cancer working group;
PSA= prostate-specific antigen;
PSMA= prostate-specific membrane antigen;
ROC= receiver operating characteristic;
Sens= sensitivity;
Spec=specificity;
WB-MRI=whole body- magnetic resonance imaging