The Science and the current use of Vacuum Therapy for ED after Radical Prostatectomy

Run Wang, MD, FACSCecil M. Crigler, MD Endowed Chair in UrologyDirector of Sexual MedicineUniversity of Texas Medical School at Houston and MD Anderson Cancer CenterHouston, TX 77030, USA

Vacuum therapy (VT) uses negative pressure to distend the corporal sinusoids and to increase blood inflow to the penis.

VCD: a constricting ring is used at the base of the penis to prevent blood outflow from the corpora cavernosa, and an erection is maintained.

VED: without a constrictive ring to increase blood oxygenation (possibly other factors in the blood) in the corpora cavernosa and also to provide stretching effect. Introduction

History of Vacuum Therapy1960sGeddins Osbon (popularizing and perfecting the device with personal used the device for more than 20 years)1917Otto Lederer (first patent-surgical device to produce erection with vacuum in conjunction with a compression ring)1874John King, MD (when there is impotency with a diminution of the size of the male organ, the glass exhauster should be applied to the part)1982Erecaid (first FDA approved VED)1986-1989 (established efficacy and safety profiles)Nadig /Witherington, MDs1996AUA (recommendation in the guidelines as one of the treatment for organic ED)

Authors Year Study design Enrollee (follow-up)Results

Nadig et al. 1986 Prospective 35 (822 months) >90% achieved adequate erections. 80% use regularlyWitherington 1989 Retrospective 1517 (8.6 months) 92% good erectionSidi et al. 1990 Prospective 100 (7.9 months) 68% satisfaction rateCookson et al. 1993 Retrospective 216 (29 months) 70% use regularly. Quality of erection plus satisfaction 490%Segenreich et al. 1993 Prospective 150 (25 months) 75% achieved adequate erection. 490% satisfaction rateBlackard et al. 1993 Prospective 45 (?) 69% satisfaction rateMeinhart et al. 1993 Prospective 74 (3 weeks) 27% satisfaction rateVrijhof et al. 1994 Prospective 67 (?)50% achieved adequate erectionBaltaci et al. 1995 Retrospective 61 (12.8 months) >80% satisfaction rate. 67% effectiveness rateBosshardt et al. 1995 Prospective 30 (6 months) Quality of erection 80%Kolettis et al. 1995 Prospective 50 (?)56% satisfaction rate. An acceptable treatment mode for CVODLewis et al. 1997 Retrospective 5847 (?) 6583% successDutta et al. 1999 Prospective 129 (37 months) High attrition rate (65%). 35% satisfaction rate

Abbreviations: CVOD, corporeal veno-occlusive dysfunction; VCD, vacuum constriction device.Efficacy of VCDs: clinic dataYuan J, Hoang An, Romero CA, Lin H, Dai Y, Wang R. IJIR 2010 , 22: 211-9

Attitudes and Practice Patterns of Penile Rehabilitation301 physicians from 41 countries83.7% performed rehabRehab strategies: - PDE5 inhibitors95.4%- ICI75.2%- VED30.2%- MUSE9.9%Reasons to not do rehab:- Cost50%- No evidence25%- not familiar25%

Penile Rehabilitation - VEDVED is gaining popularity.

MD Anderson evaluated compliance and recovery of penile length and erectile function with programmed use of VED and ICI in patients who underwent unilateral nerve-sparing prostatectomy with or without unilateral sural nerve grafting.

Changes in penile length for patients using VED (Mean SD cm) 4 mo Compliance 8 mo Compliance 12 mo Compliance

Good Poor Good Poor Good Poor

N 35 5 15 9 10 7

Length 0.4 0.8 -0.3 0.5 0.8 1.5 -0.2 1.7 0.5 06 -0.3 1.5

P value 0.05 0.22 0.32

Compared with 6 week postoperative measurement

Penile Rehabilitation - VEDRaina et al (2006) found 17% vs 11% recovery of erectile function with daily use of VED; and only 23% vs 85% reporting penile shrinkage compared with control in a 9 month study with total of 109 patients.

Kohler et al (2007) conducted a multi-centered randomized study to compare early (1 month post nerve sparing RP) to traditional (6 months after surgery) use of the VED. The preliminary results showed that early use of VED for rehabilitation (10 min a day without the constriction ring) significantly improves the IIEF-EF scores and preserves penile length compared to control group.

Penile Rehabilitation - VED

Mean O2 saturation of corporeal blood immediately after VED induced erection was 79.2% compared to 94.5% from artery and 54.7% from vein.

58% of blood with VED induced erection was arterial and 42% of blood was venous in origin.

The O2 saturation decreased significantly after 30 minutes with the ring in place. This finding established the rationale that we do not recommend using ring when VED is used for penile rehabilitation purpose.

Arterial blood may not only provide oxygen to the corporal tissues, it may also carry other nutrients such as certain growth factors to the tissues.

What is the Mechanism?

Design Rat VEDPrinciple:

Replicate human VED

Human VED

Rat VED Yuan JH, Westney OL, Wang R. JSM 6(12): 3247-53, 2009.

Pressure-Rat VEDTime (5 Min)Pressure (mmHg)Yuan JH, Westney OL, Wang R. JSM 6(12): 3247-53, 2009.

Application-Rat VEDYuan JH, Westney OL, Wang R. JSM 6(12): 3247-53, 2009.

MethodSprague-Dawley rats, weighing 200250g, were randomly and equally divided into three groups: sham (CN expose surgery only, no nerve crushing, no VED therapy); control (BCNC procedure, no VED therapy); treatment group (BCNC procedure, VED therapy beginning at 2 weeks after BCNC surgery, 5 minutes twice daily with 1 minute duration, Monday to Friday, total VED treatment time four weeks). The rat bilateral cavernous nerve crush (BCNC) model was used to replicate the pathological change of post radical prostatectomy.

Penile SizesDiameter of the penesLength of the penesLength (mm)Diameter (mm)0 4W0 4W0 4WShamBCNCBCNC+VED0 4W0 4W0 4WShamBCNCBCNC+VED**

ICP/MAP Ratios***ControlBCNCBCNC + VEDEur Urol 58: 773-80, 2010

ED after ProstatectomyNeuropraxia Reduction in arterial inflowHypoxiaApoptosisThe veno-occlusive mechanism defect EDRadical prostatectomy

VED decreases hypoxiaEur Urol 58: 773-80, 2010

TUNEL assay--cavernosal sinoidsShamBCNCBCNC+VEDVED decreases apoptosisEur Urol 58: 773-80, 2010

VED increases eNOSShamBCNCBCNC+VEDCavernosal sinoids eNOS IHC Eur Urol 58: 773-80, 2010

VED increases -SMAEur Urol 58: 773-80, 2010

VED decreases TGF-1ShamBCNCBCNC+VEDCavernosal sinoids TGF-1 IHC Eur Urol 58: 773-80, 2010

Eur Urol 58: 773-80, 2010

Conclusions

VED therapy improves erectile function and preserves penile size in rats with BCNC via anti-hypoxic, anti-apoptotic and anti-fibrotic mechanisms.

This study provides scientific evidence for VED therapy in penile rehabilitation after radical prostatectomy. This scientific evidence may motivate physicians recommendation and improve patients compliance.

Clinical studies with long-term results using VED for penile rehabilitation are not available at this time.

The multi-center, prospective study to compare the effectiveness of VED vs sildenafil in penile rehabilitation after RP should be conducted.

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