Clinical Practice Guideline for Prostate Cancer Treatment.

Full version

  1. Introduction
  2. Scope and objectives
  3. Methodology
  4. Classification of prostate cancer
  5. Localised prostate cancer
  6. Locally advanced prostate cancer
  7. Prostate cancer in PSA relapse
  8. Disseminated prostate cancer
  9. Dissemination and implementation
  10. Recommendations for future research
  11. Appendices
  12. Bibliography
  13. Full list of tables and figures

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4. Classification of prostate cancer

There are different ways of classifying patients with prostate cancer: according to the extension of the tumour (TNM), the histopathological grade (Gleason), the clinical or histopathological stage, or its risk.

4.1. TNM Classification4

T: Primary tumourd

Tx No evidence of primary tumour.
T0 Tumour not clinically apparent, not palpable or visible using imaging techniques.
T1 Tumour detected by chance in an extension less than or equal to 5% of the tissue removed.
T1a Tumour detected by chance in an extension less than or equal to 5% of the tissue removed.
T1b Tumour detected by chance in an extension greater than 5% of the tissue removed.
T1c Tumour identified by fine needle biopsy (for example, as a consequence of a high PSA).
T2 Tumour confined to the prostate.
T2a Tumour covers half of a lobe or less.
T2b Tumour covers more than half of a lobe but not both lobes.
T2c Tumour covers both lobes.
T3 Tumour extends beyond the prostatic capsule.
T3a Extracapsular extension unilateral or bilateral
T3b Tumour invades the seminal vesicle(s).
T4 Tumour is fixed or invades adjacent structures other than the seminal vesicles: bladder neck, external sphincter, rectum, upper anus muscles and/or pelvic wall.

N: Regional lymph nodese

Nx The regional lymph nodes cannot be assessed.
N0 Regional lymph node metastasis is not shown.
N1 Metastasis in regional lymph nodes.

M: Distant metastasis

  Mx Distant metastasis cannot be assessed.
  M0 There is no distant metastasis.
  M1 Distant metastasis.
  M1a Non-regional lymph node(s).
  M1b Bone(s).
  M1c Other location(s).
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4.2. Histopathological grade

The grading system proposed by Gleason et al.23 is recognised internationally, and is based on a pathological examination of prostate tissue obtained by a biopsy. The result is an average index of abnormality for the tissue, for which values between 2 and 10 can be taken17. The classification according to Gleason is as follows4:

  GX The degree of differentiation cannot be assessed.
  G1 Well differentiated (weak anaplasia): Gleason 2-4.
  G2 Moderately differentiated G2 (moderate anaplasia): Gleason 5-6.
  G3–4 Poorly differentiated/undifferentiated (marked anaplasia): Gleason 7-10.

In 2005, the International Society of Urological Pathology (ISUP)24 established an international consensus on the diagnosis of a Gleason 2-4, deciding that such a score should be an exception (only in tumours of the transition zone), and will therefore always have to be compared with another expert.


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4.3. Classification according to the clinical or pathological stage

In prostate cancer, the stage at which the patient is found is clinically defined (ie, a stage which is suspected before removing the prostate, taking into account the clinical and analytical information available at that time, which may be inaccurate or incomplete: cT1 to cT4) or pathologically defined (a stage defined on the basis of information provided by the analysis of a piece surgically extracted by radical prostatectomy: pT1 to pT4). There are different definitions for these phases4,15,17,18. For example, many studies talk about advanced prostate cancer20-30 to refer generally to the locally advanced or disseminated form. This guide uses the following definitions:

Localised prostate cancer

From an anatamopathological point of view, locally advanced prostate cancer is the verified presence of prostate adenocarcinoma with extracapsular invasion (pT3a) or invasion to the seminal vesicles (pT3b), but without lymphatic invasion (N0) nor metastasis (M0).

The patient with locally advanced prostate cancer at a clinical stage corresponds with the stage cT3, N0-Nx, M0-Mx.

Locally advanced prostate cancer

From an anatamopathological point of view, locally advanced prostate cancer is the verified presence of prostate adenocarcinoma with extracapsular invasion (pT3a) or invasion to the seminal vesicles (pT3b), but without lymphatic invasion (N0) nor metastasis (M0).

The patient with locally advanced prostate cancer at a clinical stage corresponds with the stage cT3, N0-Nx, M0-Mx.

Prostate cancer in PSA relapse

The patient with prostate cancer in PSA relapse is one who, having received primary treatment with intent to cure, has an increased PSA (prostate specific antigen) defined as "biochemical recurrence" (section 7.1 of this guide).

Disseminated prostate cancer

From an anatamopathological point of view, the patient with disseminated prostate cancer is the verified presence of prostate adenocarcinoma with lymphatic invasion (N1) and/or metastasis (M1) and/or a primary tumour which is fixed or invades adjacent structures other than the seminal vesicles (pT4).

The patient with clinically disseminated prostate cancer spread corresponds to a stage N1, M1 or cT4.


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4.4. Classification depending on the risk

The TNM clinical stage is insufficient to establish the most appropriate treatment for patients with localised prostate cancer.

Patients diagnosed with prostate cancer at localised or locally advanced clinical stages can fall into risk or prognosis subgroups on the basis of known risk factors, primarily PSA and Gleason.

This guide uses the D'Amico classification31,32:

– Low risk: cT1-cT2a, Gleason < 7 and PSA ≤ 10 ng/ml.
– Intermediate risk: cT2b, Gleason = 7 or (PSA > 10 and ≤ 20 ng/ml).
– High risk: cT2c or PSA > 20 ng/ml or Gleason > 7.

Notes

d Prostate adenocarcinoma.
e The regional lymph nodes are those in the lower pelvis (mainly, the iliopelvic lymph nodes located below the bifurcation of the primitive iliac arteries)4.

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Section 04 Bibliography

Triángulo Access to the full bibliography

 

  1. 2. Ministerio de Sanidad y Consumo. La situación del Cáncer en España. 2005.
  2. 4. European Association of Urology, Aus G, Abbou CC, Bolla M, Heidenreich A, Van Poppel H., et al. EAU Guidelines on Prostate Cancer. 2007.
  3. 5. Verdecchia A, Micheli A, Colonna M, Moreno V, Izarzugaza MI, Paci E. A comparative analysis of cancer prevalence in cancer registry areas of France, Italy and Spain. Ann Oncol. 2002;13(7):1128-39.
  4. 6. Black RJ, Bray F, Ferlay J, Parkin DM. Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990. Eur J Cancer. 1997;33(7):1075-107.
  5. 7. Centro Nacional de Epidemiología (CNE). Instituto de Salud Carlos III. Servidor Interactivo de Información Epidemiológica. Ariadna: Mortalidad por cáncer y otras causas. Gráficas. Última actualización: 6 de febrero de 2008 [consultada 10 marzo de 2008]. Available at: http://cne.isciii.es.
  6. 8. Chong CC, Austen L, Kneebone A, Lalak A, Jalaludin B. Patterns of practice in the management of prostate cancer: results from multidisciplinary surveys of clinicians in Australia and New Zealand in 1995 and 2000. BJU Int. 2006;97(5):975-80.
  7. 9. Fleshner N, Rakovitch E, Klotz L. Differences between urologists in the United States and Canada in the approach to prostate cancer. J Urol. 2000;163(5):1461-6.
  8. 10. Harlan L, Brawley O, Pommerenke F, Wali P, Kramer B. Geographic, age, and racial variation in the treatment of local/regional carcinoma of the prostate. J Clin Oncol. 1995;13(1):93-100.
  9. 15. National Comprehensive Cancer Network (NCCN). Prostate Cancer. Practice Guidelines in Oncology. 2008. Report No: v.1.2008.
  10. 17. National Institute for Health and Clinical Excellence (NICE). Clinical Guideline. Prostate Cancer: diagnosis and treatment. Evidence review. 2008 Feb.
  11. 18. AATRM (Agència d’Avaluació de Tecnologia i Recerca Mèdiques), CatSalut, Departament de Sanitat i Seguretat Social (Generalitat de Catalunya). OncoGuía de Próstata. 2004 Nov. Report No.: OG02/2004.
  12. 20. The AGREE Collaboration. AGREE Instrument Spanish version. Latest update: septiembre de 2001 [consultada 10 marzo de 2008]. Available at: http://www.agreecollaboration.org.
  13. 21. Etxeberria A, Rotaeche R, Lekue I, Callén B, Merino M, Villar M, et al. Descripción de la metodología de elaboración- adaptación- actualización empleada en la guía de práctica clínica sobre asma de la CAPV. Proyecto de Investigación Comisionada. Vitoria-Gasteiz. Departamento de Sanidad. Gobierno Vasco, 2005. Informe nº: Osteba D-05-03.
  14. 22. Scottish Intercollegiate Guidelines Network (SIGN). Edinburgh. A guideline developers’ handbook (Publication nº 50). Revised edition. Latest update: enero de 2008 [consultada 10 marzo de 2008]. Available at: http://www.sign.ac.uk/guidelines/fulltext/50/ index.html.
  15. 23. Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol. 1974;111(1):58-64.
  16. 24. Epstein JI, Allsbrook WC, Jr., Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005;29(9):1228-42.
  17. 25. Wallen MJ, Linja M, Kaartinen K, Schleutker J, Visakorpi T. Androgen receptor gene mutations in hormone-refractory prostate cancer. J Pathol. 1999;189(4):559-63.
  18. 26. Segawa N, Mori I, Utsunomiya H, Nakamura M, Nakamura Y, Shan L, et al. Prognostic signifi cance of neuroendocrine differentiation, proliferation activity and androgen receptor expression in prostate cancer. Pathol Int. 2001;51(6):452-9.
  19. 27. Miyoshi Y, Ishiguro H, Uemura H, Fujinami K, Miyamoto H, Miyoshi Y, et al. Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate cancer. Prostate. 2003;56(4):280-6.
  20. 28. Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, et al. Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res. 1994;54(20):5474-8.
  21. 29. Sadi MV, Barrack ER. Image analysis of androgen receptor immunostaining in metastatic prostate cancer. Heterogeneity as a predictor of response to hormonal therapy. Cancer. 1993;71(8):2574-80.
  22. 30. Magi-Galluzzi C, Xu X, Hlatky L, Hahnfeldt P, Kaplan I, Hsiao P, et al. Heterogeneity of androgen receptor content in advanced prostate cancer. Mod Pathol. 1997;10(8):839-45.
  23. 31. D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280(11):969-74.
  24. 32. D’Amico AV, Cote K, Loffredo M, Renshaw AA, Schultz D. Determinants of prostate cancerspecific survival after radiation therapy for patients with clinically localized prostate cancer. J Clin Oncol. 2002;20(23):4567-13.

Latest update: May 2009

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