Dr. med. Dirk Manski



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Prostate Cancer: Active Surveillance


Guidelines and review literature: (EAU Guidelines, Mottet et al, 2015) (S3-Leitlinie Prostatakarzinom der DGU) (Walsh-Campbell Urology 11th Edition).

Active Surveillance in Prostate Cancer

Active surveillance is an option for a small, well-differentiated prostate cancer and if the patient wishes a deferred treatment to avoid side effects of curative therapy. If during active surveillance a progression of the tumor occurs, curative therapy such as radical prostatectomy or radiotherapy is initiated. Several risk assessments and monitoring protocols exists to detect clinically significant prostate cancer and and to trigger active treatment. The clinical controls include, depending on the protocol and age of the patient, digital-rectal examinations, PSA and prostate needle biopsie. The following monitoring protocoll is recommended in the guideline for prostate cancer of the DGU:

Inclusion Criteria for Active Surveillance:

In the PREFERE study, patients with Gleason 7a (3 + 4) are also accepted for active surveillance, if the tumor infiltration is less than 33% in the respective core and if the longest tumor length is below 5 mm.

Follow-up of Active Surveillance:

First, quarterly, after two years then half-yearly checks with PSA testing. Digital-rectal examination every six month. A control prostate needle biopsy is recommended after 6 months, further controls are recommended every 12–18 months. After three years of stable diease, biopsies are repeated every three years.

Abort Criteria for Active Surveillance:

Active surveillance is ended if the inclusion criteria are no longer met or if the PSA doubling time is below three years. Curative therapy is recommended.

Results of Active Surveillance:

In a series of nearly 1000 patients: 76% (5 years follow-up), 64% (10 years follow-up) and 55% (15 years follow-up) of patients met the criteria of active surveillance and were not treated. 1.5% of patients died of prostate cancer and 2.8% developed bone metastases (Klotz et al, 2015). These results are comparable to curative therapy in low-risk patients. The adjuvant therapy with the 5α reduce inhibitor dutasteride could further improve these results. In a series of 302 men, 38% (with dutasteride) and 48% (with placebo) progressed under active surveillance within a three-year period (Fleschner et al, 2012).

Results of Conservative Therapy (Watchful Waiting):

Active surveillance has been developed from watchful waiting, which showed good results in good differentiated tumors. In contrast to active surveillance, conservative treatment (watchful waiting) abstains from active treatment if progress occurs in patients. If (symptomatic) metastates develop, hormone therapy is started. Conservative treatment leads within 10–15 years to a relevant cancer-specific mortality, especially in poorly differentiated tumors. For good differentiated tumors, results are favorable. For retrospective results of conservative therapy see table conservative treatment results of prostate cancer.

Results of conservative treatment of prostate cancer (watchful waiting): survival of patients with prostate cancer, age of the patients with diagnosis 55–69 years, follow-up 15 years, retrospective, n=767: for the Gleason score 2–4, 5, 6, 7, and 8–10 there is a risk of 4–6%, 6–10%, 18–27%, 70–53%, 87–72% to die from prostate cancer. The number ranges indicate the age-dependent variability, the first number applies to the group of patients 55–59 years old (age at diagnosis), the second number for the patient group 65–69 years (age at diagnosis), the patients 60–64 years old at diagnosis are in between (Albertsen et al, 1998).
Gleason- Summe Overal Survival (%) Non-cancer Mortality (%) Cancer-specific Mortality (%)
2–4 69–38 27–56 4–6
5 67–36 27–55 6–10
6 57–25 25–48 18–27
7 15–11 15–36 70–53
8–10 3 10–25 87–72








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References

Albertsen u.a. 1998 ALBERTSEN, P. C. ; HANLEY, J. A. ; GLEASON, D. F. ; BARRY, M. J.:
Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer.
In: Jama
280 (1998), Nr. 11, S. 975–80

M. A. Dall'Era, M. R. Cooperberg, J. M. Chan, B. J. Davies, P. C. Albertsen, L. H. Klotz, C. A. Warlick, L. Holmberg, D. E. Bailey, M. E. Wallace, P. W. Kantoff, and P. R. Carroll.
Active surveillance for early-stage prostate cancer: review of the current literature.
Cancer, 112 (8): 1650–1659, Apr 2008.
doi: rm10.1002/cncr.23373.
URL http://dx.doi.org/10.1002/cncr.23373.

Fleshner, N. E.; Lucia, M. S.; Egerdie, B.; Aaron, L.; Eure, G.; Nandy, I.; Black, L. & Rittmaster, R. S.
Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial.
Lancet, 2012, 379, 1103-1111.


Klotz, L.; Vesprini, D.; Sethukavalan, P.; Jethava, V.; Zhang, L.; Jain, S.; Yamamoto, T.; Mamedov, A. & Loblaw, A.
Long-term follow-up of a large active surveillance cohort of patients with prostate cancer.
J Clin Oncol, 2015, 33, 272-277.
N. Mottet (Chair), J. Bellmunt, E. Briers (Patient Representative), R.C.N. van den Bergh (Guidelines Associate), M. Bolla, N.J. van Casteren (Guidelines Associate), P. Cornford, S. Culine, S. Joniau, T. Lam, M.D. Mason, V. Matveev, H. van der Poel, T.H. van der Kwast, O. Rouvière, T. Wiegel
Guidelines on Prostate Cancer of the European Association of Urology (EAU), https://uroweb.org/guideline/prostate-cancer/.


Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF):
Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 3.1, 2014 AWMF Registernummer: 034/022OL, http://www.awmf.org/leitlinien/detail/ll/043-022OL.html (Zugriff am: 07.02.2016)


Wein, A. J.; Kavoussi, L. R.; Partin, A. P. & Peters, C. A.
Campbell-Walsh Urology
. Elsevier, 2015. ISBN 978-1455775675.


Studer, U. E.; Collette, L.; Whelan, P.; Albrecht, W.; Casselman, J.; de Reijke, T.; Knönagel, H.; Loidl, W.; Isorna, S.; Sundaram, S. K.; Debois, M. & , E. O. R. T. C. G. G.
Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 M0 prostate cancer not suitable for local curative treatment (EORTC 30891).
Eur Urol, 2008, 53, 941-949.


Wein, A. J.; Kavoussi, L. R.; Partin, A. P. & Peters, C. A.
Campbell-Walsh Urology
. Elsevier, 2015. ISBN 978-1455775675.


Tosoian, J. J.; Trock, B. J.; Landis, P.; Feng, Z.; Epstein, J. I.; Partin, A. W.; Walsh, P. C. & Carter, H. B.
Active surveillance program for prostate cancer: an update of the Johns Hopkins experience.
J Clin Oncol, 2011, 29, 2185-2190.


Wilt, T. J.; Brawer, M. K.; Jones, K. M.; Barry, M. J.; Aronson, W. J.; Fox, S.; Gingrich, J. R.; Wei, J. T.; Gilhooly, P.; Grob, B. M.; Nsouli, I.; Iyer, P.; Cartagena, R.; Snider, G.; Roehrborn, C.; Sharifi, R.; Blank, W.; Pandya, P.; Andriole, G. L.; Culkin, D.; Wheeler, T. & PIVOT Study Group
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