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Re: Prostate-Specific Antigen Kinetics During Follow-Up Are an Unreliable Trigger for Intervention in a Prostate Cancer Surveillance Program

By: Patrick J. Bastian

European Urology, Volume 58 Issue 5, November 2010

Published online: 01 November 2010

Abstract Full Text Full Text PDF (45 KB)


Ross AE, Loeb S, Landis P, et al
J Clin Oncol 2010;28:2810–6
Expert’s summary:
The aim of the study was to investigate the predictive ability of prostate-specific antigen (PSA) velocity and PSA doubling time (PSA DT) for biopsy progression and adverse pathologic outcome at prostatectomy in men with low-risk prostate cancer (PCa) who were enrolled in an active surveillance protocol. Of 290 men, 65% remained on active surveillance, whereas 35% developed biopsy progression at a median of 2.9 yr. PSA DT was not associated and PSA velocity (PSAV) was marginally associated with subsequent pathologic findings. Furthermore, PSAV and PSA DT were not associated with the presence of unfavorable pathology in men undergoing radical prostatectomy.
Expert’s comments:
Active surveillance has emerged as a treatment option for insignificant PCa and is part of the current treatment guidelines [1] and [2]. Epstein et al introduced prostate biopsy criteria to predict insignificant PCa [2].These criteria include clinical stage T1c, PSA density <0.15 ng/ml, no Gleason pattern 4 or 5, less than three positive cores, and <50% cancer per core [3]. In addition to the original Epstein criteria, multiple selection criteria for insignificant PCa based on preference or experience have been reported. Using tables or current nomograms, one may better predict the estimated individual risk of a patient [4].

Multiple studies have examined the outcome of significant and insignificant cancer. In the pioneering work of Epstein et al, their criteria correctly predicted the presence of pathologically insignificant PCa (tumor volume <0.2 cm3, pathologic Gleason score ≤6, and organ-confined disease) in 73% of all cases (41 of 157 cases) [3]. A contemporary update included a cohort of 237 nonpalpable (clinical stage T1c) PCa patients treated with radical prostatectomy at Johns Hopkins Hospital [5]. Within that cohort, 91.6% of cases fulfilled the Epstein criteria that correctly predicted the presence of organ-confined disease [5]. This in itself demonstrates that the criteria are stringent and useful.

One major problem remains. As reported, all patients have to undergo very close and active monitoring so that progression of their insignificant cancer to potentially significant cancer will not be missed. According to a recent review, follow-up investigations every 3 mo are necessary, and an additional biopsy every 12–18 mo is mandatory [2]. Fujita et al. [8] recently reported the side effects of serial prostatic biopsies with increased erectile dysfunction.

In the study by Ross et al, the use of PSA kinetics as a trigger for intervention in a surveillance program was tested. As stated, the postdiagnostic PSA kinetics cannot reliably predict adverse pathology and cannot replace the annual biopsy in monitoring patients.

This is rather disappointing and unexpected compared with the findings of other groups [6] and [7]; PSA kinetics are easy to use and are available in these cohorts. Other studies have shown the beneficial use of PSA kinetics in the diagnostic and prognostic setting of PCa. Nevertheless, the study by Ross et al underscores that PSA kinetics will not serve as a sole marker to help solve the problem. A combination of novel progression markers and modern imaging techniques may improve the identification of patients needing active treatment of PCa.

Conflicts of interest

The author has nothing to disclose.

References

  • [1] A. Heidenreich, G. Aus, M. Bolla, et al. EAU guidelines on prostate cancer. Eur Urol. 2008;53:68-80 Crossref
  • [2] P.J. Bastian, B.H. Carter, A. Bjartell, et al. Insignificant prostate cancer and active surveillance: from definition to clinical implications. Eur Urol. 2009;55:1321-1332 Crossref
  • [3] J.I. Epstein, P.C. Walsh, M. Carmichael, C.B. Brendler. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994;271:368-374 Crossref
  • [4] F.K. Chun, A. Haese, S.A. Ahyai, et al. Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men. Cancer. 2008;113:701-709 Crossref
  • [5] P.J. Bastian, L.A. Mangold, J.I. Epstein, A.W. Partin. Characteristics of insignificant clinical T1c prostate tumors. A contemporary analysis. Cancer. 2004;101:2001-2005 Crossref
  • [6] M.K. Ng, N. Van As, K. Thomas, et al. Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time. BJU Int. 2009;103:872-876 Crossref
  • [7] A.J. Stephenson, A.G. Aprikian, L. Souhami, et al. Utility of PSA doubling time in follow-up of untreated patients with localized prostate cancer. Urology. 2002;59:652-656 Crossref
  • [8] K. Fujita, P. Landis, B.K. McNeil, et al. Serial prostate biopsies are associated with an increased risk of erectile dysfunction in men with prostate cancer on active surveillance. J Urol. 2009;182:2664-2669 Crossref

Footnotes

Urologische Klinik und Poliklinik, Klinikum der Universität – Campus Großhadern, Ludwig-Maximilians-Universität München, München, Germany

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