Treatment Mapping of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia-an Analysis of the Governing Body of German Prostate Centers - Beyond the Abstract

Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) represent one of the most common urological syndromes. In men older than 50 years, 40.5% suffer from symptoms requiring treatment, 26.9% have an enlarged prostate gland volume > 25 ml and 17.3% a weakening of the urinary stream.1



In contrast to prostate carcinoma, which is systematically recorded in specific tumor registers and prostate carcinoma centers,2 such registers for LUTS/BPH are rare. Against the background of the demographic development and the expected increase in treatment cases of LUTS/BPH in the coming years, the necessity of such registers for this entity becomes evident.

The database of “Uro Cert” prostate centers from the “Governing Body of German Prostate Centers” offers one possibility to generate healthcare data for LUTS/BPH. “Uro Cert” has been certifying networks of urological clinics and urologists in private practice since 2005 with the aim of improving the cross-sectoral (inpatient and outpatient) and interdisciplinary care of patients with prostatic diseases, such as prostate carcinoma, LUTS/BPH and prostatitis. At present, 22 intersectoral networks hold a valid certificate as a "prostate center" nationwide, including two university hospitals, 19 non-academic hospitals, three private clinics, and 270 “office-based” urologists.  

The “Uro Cert” certificate requirements concern certain standards for diagnosis and therapy, including the quality of outcomes to be achieved.3 Patient data on diagnosis, therapy, and course of disease are also systematically documented in a central database (UroCloud).

In total 18,299 pseudonymized LUTS/BPH patients were documented, of which 15,306 patients (83.6%) received one form of therapy, 2,672 patients (14.6%) two forms of therapy and 321 patients (1.8%) all three possible forms of therapy ("wait and see", drug, instrument). The median observation periods of the clinical courses diverge depending on the different forms of therapy. They are shortest for the instrumental therapy alone (one month) and longest at 65 months for patients who received all three therapy lines.  

Of 8,626 patients, who received a medical treatment the vast majority (56%) received alpha-blockers, whereas phytotherapeutic agents were used least frequently (3%). The median age at the beginning of therapy with alpha-blockers was 67 years (IQR 59-74). Patients with 5-alpha-reductase inhibitors (5-ARI), the combination alpha blocker/5-ARI or anticholinergics were the oldest in the median age group at 71 years, patients with phosphodiesterase (PDE)-5-inhibitors were the youngest at 59 years. 

Patients with alpha-blockers had a median prostate volume of 40 ml (IQR 30-53). Patients under the combination alpha blocker/5-ARI (60ml, IQR 48-80) had the largest prostate volumes, patients with PDE-5 inhibitors (33ml, IQR 28-42) and phytotherapeutic drugs (33ml, IQR 25-44) had the smallest prostate volumes.

Patients with alpha-blockers or the combination alpha blocker/5-ARI had the strongest symptoms with a median International Prostate Symptom Score (IPSS) of 15 points (IQR 10-21). Patients with PDE-5 inhibitors had the least severe symptoms (7 points, IQR 4-14).

Of 14,337 patients that received an instrumental therapy, 14,290 could be assigned to primary instrumental therapy. Of these, 8,570 (60.0%) received a transurethral resection of the prostate (TUR-P), 1,339 (9.4%) an open prostatectomy (OP), 710 (5.0%) a laser therapy (LT), 2,608 (18.3%) an indwelling catheter and 1,063 (7.4%) "other" instrumental therapy (e.g. transurethral microwave thermotherapy = TUMT, stent, UroLift®, etc).  

In order to compare the three most frequently used "definitive" therapies TUR-P, OP and LT, all patients with one of these therapies and complete documentation of the basic parameters were considered: of a total of 10,420 patients, 8,389 (80.5%) received TUR-P, 1,334 (12.8%) received surgery and 697 (6.7%) LT. Patients with TUR-P and OP were slightly younger than patients with LT (72 years vs. 73 years; p=0.032). Patients with surgery had larger prostate volumes than patients with TUR-P and LT (87 ml vs. 45 ml; p<0.001). The IPSS score (symptoms/quality of life) was the same for all three treatment forms at 19/4 (p=0.684) (Table 1).

Table 1. IPSS score across TUR-P, OP, and LT treatments for patients
symptoms and quality of life table
The median hospital stay was six days (IQR 4-7) for TUR-P, nine days (IQR 7-11) for surgery and five days (IQR 4-6) for LT (p< 0.001) (Figure 1). For TUR-P, OP and LT the transfusion rates were 1.7%, 4.1% and 1.0% (p< 0.001); re-intervention rates were 6.4%, 5.6% and 4.6% (p< 0.001) (Figure 2).

days of hospitalization
Figure 1. Days of hospitalization (Median, IQR, Min, Max)

transfusion and re invention rates
Figure 2. Transfusion- and re-intervention rates

Discussion

In the “Uro Cert” prostate centers, nearly 30,000 treatments for LUTS/BPH have been documented in the last 12 years. It is important that these centers include university institutions, primary care facilities, private clinics, and office-based urologists, and that out-patient care is structurally integrated. Thus the entire spectrum of care is represented. From the very beginning, importance was attached to the documentation of clinical care data. While the observation periods for the majority of instrumental therapies (< 1 month) still mainly cover the short-term post-operative period, patients who received all three lines of therapy (wait-and-see, medication, instrumental) already have a meaningful medium- to long-term course at 65 months. 

This analysis shows that age, prostate volume, and IPSS are increasing in the "wait and see" therapy cascade → medically → surgically/instrumentally. This escalation of the therapies according to the symptoms suggests that the allocation to the respective therapy options is correct.

The investigation of medical treatment confirms the dominance of alpha-blockers despite the increasing use of therapeutic alternatives. From 2012-2017, a significant increase in the prescription of anticholinergics and PDE-5 inhibitors has been demonstrated.4 It was noticeable that patients on PDE-5 inhibitors with a median IPSS score (symptoms/quality of life) of 7/1 had by far the least complaints, which according to official classification are classified as mild symptoms. In contrast, the currently valid European guideline recommends the use of drug therapy only if the symptoms are moderate to severe (IPSS ≥ 8).5 One reason for this could be that PDE-5 inhibitors cause fewer side effects (e.g. ejaculation disorders) and are therefore used in everyday care even when symptoms are less severe. Another possibility would be to use them primarily in patients with additional erectile dysfunction. A comparison of the respective IIEF (International Index of Erectile Function) scores of patients under medical treatment would thus be a logical consequence that can be represented by the “Uro Cert” database. The latter observation in particular is a good example of the strength of health services research in that it examines the "reality" of medical care and thus answers questions that neither basic biomedical research nor classical clinical research can answer.

The prostate volume appears to be the primary factor in the choice of surgical therapy. Accordingly, patients with OP had significantly larger prostate volumes than TUR-P or LT patients. It can be clearly seen that the choice of therapy is independent of the symptoms, as the IPSS scores of the groups did not differ (19/4; p=0.684).

However, age also seems to play a role in therapy selection, with LT patients being slightly, but statistically significant, older at 73 years (vs. 72 years) (p=0.032). Here, a tendency can be seen to provide "older" patients with the supposedly least stressful therapy. This approach is confirmed by the postoperative results: LT patients had the shortest hospital stay as well as the lowest transfusion and re-intervention rates.

In the future, the evaluation of functional parameters in the medium to long term will be of particular interest. Here, for example, a dedicated examination of the different laser procedures (vaporization, enucleation) could show whether one of these procedures can confirm or even improve the known good long-term results of TUR-P. If this is the case, these treatment data could then have therapeutic implications for practice. 

Written by:  J. Herden,1,2 T. Ebert,1,3 D. Schlager,4 W. Diederichs,5 J. Zumbe,6 H.-J. Sommerfeld,7  W. Schafhauser,8 M. Kriegmair,9 M. Garcia Schürmann,10 F. Distler,11 H. Baur,12 F. Oberpenning,13  M. Reimann,14 G. Haupt,15 K. Hoefner,16 S. Laabs,17 B. Planz,18 E. Gronau,19 G. Platz,20  S. Buse,21 J. Jones,22 A. Heidenreich,2 H. Ruebben,1 W. Schultze-Seemann,1,4 P. Weib,1,23

1Governing Body of German Prostate Centers, Berlin, Germany, 2Prostatecenter Cologne, Cologne, Germany, 3Prostatecenter Metropolregion Nuremberg, Fuerth, Germany,  4Prostatecenter Freiburg, Freiburg, Germany, 5Prostatecenter Berlin, Berlin, Germany, 6Prostatecenter Leverkusen, Leverkusen, Germany, 7Prostatecenter Marl, Marl, Germany, 8Prostatecenter Hochfranken-Fichtelgebirge, Marktredwitz, Germany, 9Urology Center Munich, Planegg, Germany, 10Prostatecenter Niederrhein, Wesel, Germany, 11Prostatecenter Nuremberg-Middle Franconia, Nuremberg, Germany, 12Prostatecenter Nymphenburg, Munich, Germany, 13Prostatecenter Bocholt, Bocholt, Germany, 14Prostatecenter Moers, Moers, Germany, 15Prostatecenter Speyer, Speyer, Germany, 16Prostatecenter Rhine-Ruhr, Oberhausen, Germany,17Prostatecenter Elbe-Weser, Stade, Germany, 18Prostatecenter Emscher-Lippe, Gladbeck, Germany, 19Prostatecenter Muensterland, Muenster, Germany, 20Prostatecenter Mainspitze, Ruesselsheim, Germany, 21Prostatecenter Alfred Krupp-Hospital, Essen, Germany, 22Prostatecenter Hochtaunus, Bad Homburg, Germany, 23Prostatecenter Siegen-Wetzlar, Siegen, Germany

References:

  1. Berges, Richard R., L. Pientka, K. Höfner, T. Senge, and U. Jonas. "Male lower urinary tract symptoms and related health care seeking in Germany." European urology 39, no. 6 (2001): 682-687.
  2. Fichtner, J., C. Kowalski, S. Wesselmann, and P. Albers. "Indicator analysis of prostate cancer centers certified by the German Cancer Society 2015." Der Urologe. Ausg. A 54, no. 11 (2015): 1530-1532.
  3. Brehmer, B., R. Berges, T. Ebert, M. Goepel, and A. Heidenreich. "Documentation of the Governing Body of Prostate Centers (DVPZ)." Der Urologe. Ausg. A 52, no. 3 (2013): 408.
  4. Herden, J., T. Ebert, D. Schlager, J. Pretzer, J. Zumbé, H. J. Sommerfeld, W. Schafhauser et al. "Versorgungsabbild des benignen Prostatasyndroms eine Analyse des Dachverbandes der Prostatazentren Deutschlands (DVPZ) e. V." Urologie; Ausg. A. z. klin. prakt (2020).
  5. Ljungberg, B., L. Albiges, K. Bensalah, A. Bex, R. H. Giles, and M. Hora. "EAU guidelines. Edn. presented at the EAU annual congress Barcelona 2019. EAU Guidelines Office, Arnhem."
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