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Clinical Research

Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy

Abstract

Background:

The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT).

Methods:

This was a single-institution retrospective analysis from 1987 to 2009 of 13 427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n=415), antiandrogen therapy alone (n=400) and combined treatment (n=333). Kaplan–Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse.

Results:

Median duration of NHT was 3 months (interquartile range (IQR) 2–4) whereas median follow-up after RP was 8.3 years (IQR 5–10.8). NHT patients were more likely to be D’Amico high risk, have locally advanced pathologic T stage (≥pT3), pathologic Gleason scores (GS) of 8–10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P≤0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P=0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P<0.0001).

Conclusions:

Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

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References

  1. Vailancourt L, Ttu B, Fradet Y, Dupont A, Gomez J, Cusan L et al. Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma. A randomized study. Am J Surg Pathol 1996; 20: 86–93.

    Article  CAS  Google Scholar 

  2. Civantos F, Marcial MA, Banks ER, Ho CK, Speights VO, Drew PA et al. Pathology of androgen deprivation therapy in prostate carcinoma. A comparative study of 173 patients. Cancer 1995; 75: 1634–1641.

    Article  CAS  Google Scholar 

  3. Selli C, Montironi R, Bono A, Pagano F, Zattoni F, Manganelli A et al. Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer. J Clin Pathol 2002; 55: 508–513.

    Article  CAS  Google Scholar 

  4. Soloway MS, Sharifi R, Wajsman Z, McLeod D, Wood DP Jr, Puras-Baez A . Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group. J Urol 1995; 154 (2 Pt 1): 424–428.

    Article  CAS  Google Scholar 

  5. Bullock MJ, Srigley JR, Klotz LH, Goldenberg SL . Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma: a detailed analysis of radical prostatectomy specimens from a randomized trial. Am J Surg Pathol 2002; 26: 1400–1413.

    Article  Google Scholar 

  6. Grignon DJ, Bostwick DG, Civantos F, Garnick MB, Gaudin P, Srigley JR . Pathologic handling and reporting of prostate tissue specimens in patients receiving neoadjuvant hormonal therapy: report of the Pathology Committee. Mol Urol 1999; 3: 193–198.

    CAS  PubMed  Google Scholar 

  7. Hellstrom M, Haggman M, Brandstedt S, de la Torre M, Pedersen K, Jarlsfeldt I et al. Histopathological changes in androgen-deprived localized prostatic cancer. A study in total prostatectomy specimens. Eur Urol 1993; 24: 461–465.

    Article  CAS  Google Scholar 

  8. Polito M, Muzzonigro G, Minardi D, Montironi R . Effects of neoadjuvant androgen deprivation therapy on prostatic cancer. Eur Urol 1996; 30 (Suppl 1): 26–31.

    Article  Google Scholar 

  9. Reuter VE . Pathological changes in benign and malignant prostatic tissue following androgen deprivation therapy. Urology 1997; 49 (3A Suppl): 16–22.

    Article  CAS  Google Scholar 

  10. Tetu B, Srigley JR, Boivin JC, Dupont A, Monfette G, Pinault S et al. Effect of combination endocrine therapy (LHRH agonist and flutamide) on normal prostate and prostatic adenocarcinoma. A histopathologic and immunohistochemical study. Am J Surg Pathol 1991; 15: 111–120.

    Article  CAS  Google Scholar 

  11. Efstathiou E, Abrahams NA, Tibbs RF, Wang X, Pettaway CA, Pisters LL et al. Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification. Eur Urol 2010; 57: 1030–1038.

    Article  Google Scholar 

  12. Epstein JI, Allsbrook WC Jr., Amin MB, Egevad LL, Committee IG . The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005 29: 1228–1242.

  13. Algaba F, Epstein JI, Aldape HC, Farrow GM, Lopez-Beltran A, Maksem J et al. Assessment of prostate carcinoma in core needle biopsy—definition of minimal criteria for the diagnosis of cancer in biopsy material. Cancer 1996; 78: 376–381.

    Article  CAS  Google Scholar 

  14. Edge SB, Compton CC . The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010; 17: 1471–1474.

    Article  Google Scholar 

  15. Epstein JI, Allsbrook WC Jr., Amin MB, Egevad LL . Update on the Gleason grading system for prostate cancer results of an international consensus conference of urologic pathologists. Adv Anat Pathol 2006; 13: 57–59.

    Article  Google Scholar 

  16. Amling CL, Bergstralh EJ, Blute ML, Slezak JM, Zincke H . Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point? J Urol 2001; 165: 1146–1151.

    Article  CAS  Google Scholar 

  17. Stephenson AJ, Kattan MW, Eastham JA, Dotan ZA, Bianco FJ Jr, Lilja H et al. Defining biochemical recurrence of prostate cancer after radical prostatectomy: a proposal for a standardized definition. J Clin Oncol 2006; 24: 3973–3978.

    Article  CAS  Google Scholar 

  18. Chung PH, Gayed BA, Thoreson GR, Raj GV . Emerging drugs for prostate cancer. Expert Opin Emerg Drugs 2013; 18: 533–550.

    Article  CAS  Google Scholar 

  19. Bentley G, Dey J, Sakr WA, Wood DP Jr, Pontes JE, Grignon DJ . Significance of the Gleason scoring system after neoadjuvant hormonal therapy. Mol Urol 2000; 4: 125.

    CAS  PubMed  Google Scholar 

  20. O'Brien C, True LD, Higano CS, Rademacher BL, Garzotto M, Beer TM . Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer. Am J Clin Pathol 2010; 133: 654–661.

    Article  Google Scholar 

Download references

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Correspondence to R J Karnes.

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Stewart, S., Cheville, J., Sebo, T. et al. Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy. Prostate Cancer Prostatic Dis 17, 332–337 (2014). https://doi.org/10.1038/pcan.2014.30

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