Volume 132, Issue 2 p. 217-226
Original Article
Open Access

Efficacy of RestoreX after prostatectomy: open-label phase of a randomized controlled trial

Andrew Zganjar

Andrew Zganjar

Mayo Clinic, Rochester, MN, USA

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Amir Toussi

Amir Toussi

University of Pittsburgh Medical Center, Pittsburgh, PA, USA

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Matthew Ziegelmann

Matthew Ziegelmann

Mayo Clinic, Rochester, MN, USA

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Igor Frank

Igor Frank

Mayo Clinic, Rochester, MN, USA

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Stephen A. Boorjian

Stephen A. Boorjian

Mayo Clinic, Rochester, MN, USA

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Matthew Tollefson

Matthew Tollefson

Mayo Clinic, Rochester, MN, USA

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Tobias Köhler

Tobias Köhler

Mayo Clinic, Rochester, MN, USA

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Landon Trost

Corresponding Author

Landon Trost

Mayo Clinic, Rochester, MN, USA

Male Fertility and Peyronie's Clinic, Orem, UT, USA

Correspondence: Landon Trost, 1443 W 800 N, Suite 302, Orem, UT 84057, USA.

e-mail: [email protected]

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First published: 23 April 2023
Citations: 3

Abstract

Objective

To report open-label phase data from a recent randomized controlled trial (RCT), after previous data from that study showed improved penile length and erectile function among post-prostatectomy men treated with Restorex penile traction therapy (RxPTT).

Materials and Methods

An RCT (NCT05244486) was performed to evaluate RxPTT vs no treatment (Tx) for 5 months, which was followed by a 3-month open-label phase. Men were stratified based on as-treated data: Group 1 = No Tx; Group 2 = No Tx → Tx; Group 3 = Tx → No Tx; Group 4 = Tx. Assessments included stretched penile length and standardized (International Index of Erectile Function [IIEF]) and non-standardized questionnaires.

Results

A total of 82 men were enrolled (mean age 58.6 years) with 9-month data available in 45 of the men. Baseline characteristics were similar among the cohorts. Comparing Group 1 and Group 4 (respectively), notable differences included: IIEF Erectile Function domain (IIEF-EF) score (−8 vs −0.5; P = 0.16), penile length (−0.1 vs +1.7 cm; P < 0.01), intracavernosal injection use (86% vs 14%; P < 0.01), Sexual Encounter Profile (SEP) Question 2 (50% vs 100%; P < 0.01), SEP Question 3 (33% vs 100%; P < 0.01). Men who crossed over to Tx (Group 2) failed to achieve equivalent improvements in length (+0.5 cm) or sexual function (IIEF-EF score −6) compared to men treated early (Groups 3 and 4). Those who crossed over to no treatment after initial treatment (Group 3) experienced preserved length (+1.8 cm), and erectile function (IIEF-EF score +0) despite therapy discontinuation.

Conclusions

Use of RxPTT beginning 1 month post-prostatectomy results in improved penile length and erectile function, with benefits maintained after discontinuing therapy. If confirmed, these results represent the first postoperative therapy shown in a RCT to improve erectile function post-prostatectomy. External validation is warranted.

Introduction

The treatment of prostate cancer continues to evolve, with multiple contemporary therapies available, including surgery, directed/thermal energy, radiation and hormone/immune manipulation, among others. However, despite the ongoing innovations, arguably, all mainstream, curative treatments are associated with some degree of bothersome sexual dysfunction. Specifically, sexual dysfunction after definitive prostate cancer therapy commonly includes erectile dysfunction (ED), ejaculatory dysfunction, climacturia, de novo Peyronie's disease, and changes to orgasm and libido. The impact of prostate cancer therapies on penile length remains controversial, however, with a discrepancy often noted in subjective reports of decreased length, despite no measurable changes being observed objectively [1-4].

Given the significant impact of ED on quality of life, several studies have investigated how to preserve or improve erectile function post-prostatectomy. Two large, adequately powered, randomized controlled trials (RCTs) evaluated the role of phosphodiesterase-5 (PDE5) inhibitors post-prostatectomy and demonstrated no improvements in erectile function following washout [5, 6]. Additionally, no RCTs of vacuum erection devices have been performed evaluating erectile function after a washout period post-prostatectomy [7]. Intracavernosal injection (ICI) therapies have also been investigated, with one randomized trial failing to demonstrate differences between groups treated with varying schedules of PDE5 inhibitors and ICIs [8]. However, it is noteworthy that the trial closed early due to poor enrolment.

Recently, a novel, second-generation penile traction therapy (PTT) device was developed (Restorex; PathRight Medical, Plymouth, MN, USA) to improve penile length and curve in men with Peyronie's disease. Compared to first-generation devices, which all use a similar traction mechanism (e.g. Andropenis [Andromedical, Madrid, Spain], PeniMaster [MSP Concept GmbH & Co. KG, Berlin, Germany], X4 Labs [X4 Labs Canada Inc., Vaudreuil-dorion, Quebec, Canada], Phallosan Forte [Orbisan Ltd, San Gwann, Malta]), Restorex PTT (RxPTT) introduced several characteristics which allowed greater application of traction forces, including a modified penile clamping mechanism (which displaces force more broadly to the head of the penis), counterbending (not applicable in the current study), stronger mechanical springs, wider displacement base (to better displace the greater forces), and dynamic adjustment of traction during use. Due to these changes, initial clinical trials of RxPTT in men with Peyronie's disease demonstrated consistent improvements in length and curve with 30 min of daily use, compared to variably effective outcomes with 2–9 h of daily use required for first-generation devices [9-14]. Unexpectedly, the data also demonstrated improvements in erectile function, which was of unclear significance initially.

Given, these observations and the known impacts of prostatectomy on subjective penile length and erectile function, an RCT was designed to evaluate the efficacy of Restorex PTT (RxPTT) in men post-prostatectomy [4]. Men randomized to the treatment arm began RxPTT for 30–60 min daily for 5–7 days/week, starting at 1 month post-prostatectomy. Compared to the no-PTT controls, results demonstrated statistically significant improvements in penile length and preserved erectile function in men treated with RxPTT. Other non-standardized subjective measures of length and erectile function and indirect measures of erectile function (i.e., percentage of men using ICI) confirmed objective/standardized findings.

The objective of the current study was to report outcomes of the open-label phase from the previously described RCT. The primary intent of the open-label phase was to address two key questions through examination of crossover data: (i) Are observed improvements in length/erectile function maintained despite treatment discontinuation; and (ii) Do men who begin RxPTT after a delay (i.e., 6 months postoperatively) experience similar benefits to those treated early.

Materials and Methods

Study Protocol and Design

The current study was designed as a prospective RCT evaluating the use of RxPTT in men who have undergone prostatectomy (NCT03500419). After institutional review board approval and informed consent had been obtained, study participants were randomized 2:1 to RxPTT or control (no RxPTT) beginning at 1 month post-prostatectomy and continuing until 6 months postoperatively. Study participants then entered a 3-month open-label phase, in which they were permitted to utilize RxPTT. The current study reports the outcomes of the open-label phase. For a more detailed explanation of the study protocol (Fig. 1), including results from the randomization phase, please refer to the earlier publication [4].

Details are in the caption following the image
Study protocol; the current paper reports outcomes of the 9-month assessments (end of open-label phase).

All men undergoing robotic prostatectomy were candidates for study inclusion, with the only exclusion criterion being urethral complications either during or within the first month post-prostatectomy.

Treatment Protocol

After completion of the randomization phase (6 months postoperatively), all men were permitted to utilize RxPTT if desired. Men performed straight traction only and were recommended to use the device for 30–60 min daily if choosing this treatment. All men were permitted to use PDE5 inhibitors or ICIs if desired or recommended by their treating clinicians.

Categorization of Cohorts

To evaluate outcomes of the open-label phase, men were classified into one of four cohorts based on average device utilization during the initial randomization phase and subsequent open-label phase: Group 1: Initially no treatment followed by mean RxPTT use <15 min/day (No Tx); Group 2: Initially no treatment, followed by mean use >15 min/day (No Tx → Tx); Group 3: Initially RxPTT group, followed by mean use <15 min/day (Tx → No Tx); and Group 4: Initially RxPTT group, followed by mean use >15 min/day (Tx). The selection of 15 min/day was based on findings from prior studies that demonstrated significant improvements when utilization exceeded this threshold [4, 9].

Outcome Measures

All men were requested to maintain daily PTT utilization diaries throughout all phases of the study. Other assessments were obtained at baseline and at 6 months (conclusion of RCT) and 9 months (end of open-label phase) post-prostatectomy. Objective evaluations of stretched penile length (pubis to corona and pubis to tip) were performed in duplicate (two providers), while subjective measures included standardized (International Index of Erectile Function [IIEF]), non-standardized, and adverse event questionnaires.

Data Presentation and Statistical Analyses

Normally distributed data are reported as means and standard deviations, while non-normal distributions are presented as medians and interquartile ranges. Key outcomes were compared either among all four groups or between Groups 1 and 4 (to represent an as-treated analysis), depending on the specific measure and as indicated in the specific analysis.

Statistics were performed using JMP 14.2.0 (SAS Institute, Minneapolis, MN, USA), with Student's t-tests, Wilcoxon, or chi-squared tests used based on data type. Multivariable, logistic regression was performed to evaluate whether either the grouping (i.e., early vs late treatment) or total duration of treatment (in 10-h increments) was independently associated with improvements in penile length and IIEF-EF scores. P values (two-tailed) of <0.05 were taken to indicate statistical significance.

Results

A total of 82 men were enrolled between April 2018 and February 2020, with 9-month data available in 45 men (Group 1, n = 9; Group 2, n = 9; Group 3, n = 13; Group 4, n =14). Baseline demographics and clinicopathological variables were similar in the RxPTT and the control groups, with the exception of baseline PSA level, which was higher in the RxPTT group (Table 1). Average device utilization over the entire study period varied by grouping (Group 1 mean [SD; range] 1.5 [2.0; 0–4.7] min/day; Group 2 mean [SD; range] 15.4 [5.9; 7.5–24.4] min/day; Group 3 mean [SD; range] 18.1 [12.4; 0–42.3] min/day; Group 4 mean [SD; range] 33.4 [14.0; 19–59.4] min/day).

Table 1. Patient baseline demographic, clinicopathological and surgical variables.
Variable* No 9-month data, n = 37 Group 1, n = 9 No PTT × 8 months (No Tx) Group 2, n = 9 No PTT × 5 months, PTT × 3 months (No Tx → Tx) Group 3, n = 13 PTT × 5 months, No PTT × 3 months (Tx → No Tx) Group 4, n = 14 PTT × 8 months (Tx) P
Age, mean (sd) years 56.5 (6.4) 58.2 (5.0) 59.4 (4.4) 62.9 (6.6) 59.6 (4.3) 0.02
IIEF, all median (IQR)
EF domain 27 (9, 30) 28 (16, 30) 25 (9, 30) 28 (5, 30) 27 (9, 29) 0.87
Orgasmic function domain 10 (8, 10) 10 (5, 10) 10 (9, 10) 9 (2, 10) 10 (5, 10) 0.58
Sexual desire domain 8 (6, 10) 9 (7, 10) 9 (7, 10) 7 (4, 9) 6 (5, 8) 0.21
Intercourse satisfaction domain 11 (1, 12) 12 (5, 14) 12 (4, 14) 9 (0, 13) 9 (0, 12) 0.38
Overall satisfaction domain 8 (6, 10) 10 (5, 10) 8 (6, 10) 8 (3, 10) 8 (6, 10) 0.88
ED categorization, %
No ED 58 56 44 54 57 0.97
Mild ED 11 22 22 8 14
Mod ED 3 11 11 8 7
Severe ED 28 11 22 31 21
Self-reported ED, % 32 56 44 46 29 0.61
Duration of ED, median (IQR) months 42 (15, 69) 36 (14, 144) 26 (24, 97) 24 (3, 75) 45 (14, 288) 0.92
Use of PDE5 inhibitors within past year, % 16 56 33 23 21 0.21
Use of ICIs within past year, % 0 0 11 0 0 0.34
Self-reported pre-operative curvature, % 19 33 11 8 14 0.58
Self-reported pre-operative penile length loss, % 8 38 11 23 15 0.32
Estimated amount of length loss, median cm (IQR) 2.8 (2.5, 3) 1 (1, 2) 1 (1, 1) 1 (1, 1) 1 (1, 2) 0.26
Surgical and pathologic variables
Preoperative PSA, median (IQR) ng/mL 7 (5, 11) 5 (4, 10) 4 (3, 11) 7 (5, 10) 9 (5, 11) 0.11
Perineural invasion (on biopsy), % 11 33 22 15 29 0.44
Approach, % robotic (vs open) 100 89 100 100 100 0.34
Gleason score, %
3 + 3 11 22 11 8 7 0.74
3 + 4 57 44 89 54 64
4 + 3 5 0 0 0 0
4 + 4 16 22 0 23 21
4 + 5 3 0 0 0 0
5 + 4 8 11 0 15 0
5 + 5 0 0 0 0 7
Pathological stage, %
T2 78 89 100 69 86 0.55
T3a 14 11 0 15 7
T3b 8 0 0 15 7
Pathological node status, %
Nx 24 33 22 15 14 0.56
N0 73 67 78 69 86
N1 3 0 0 15 0
Metastatic disease, % positive 0 0 0 8 7 0.34
Surgical margin positive, % 14 22 33 25 29 0.61
Nerve-sparing, %
None 0 0 0 0 7 0.26
Unilateral 14 22 0 0 14
Bilateral 86 78 100 100 79
ADT within 6 months of surgery, % 3 0 0 8 0 0.63
Radiation within 6 months of surgery, % 3 0 0 0 0 0.78
Biochemical recurrence at last follow-up, % 9 11 0 15 14 0.64
  • Wilcoxon tests used for continuous, non-parametric data, Student's t-tests for continuous, parametric data, and Fisher's exact and likelihood ratio tests for categorical variables.
  • ADT, androgen deprivation therapy; ED, erectile dysfunction; EF, erectile function domain; ICI, intracavernosal injection; IIEF, International Index of Erectile Function; IQR, interquartile range; PDE5, phosphodiesterase-5; PTT, penile traction therapy; Tx, treatment.
  • * Number of participants varies within each group by variable; missing data points were not replaced/imputed.

Group 1 (No Treatment) vs Group 4 (RxPTT × 8 Months)

Table 2 and Fig. 2 show key outcomes including objective, standardized, and non-standardized assessments. Men who utilized RxPTT for >15 min/day × 8 months (Group 4) demonstrated greater length improvements (1.7 cm [pubis to corona]; P < 0.01) than those who chose not to utilize traction (Group 1), consistent with previously published findings during the randomization phase. Men who chose treatment also reported greater overall satisfaction with penile length (satisfied 78.5 vs 14.3; P < 0.05), higher rates of reported improvement in length (71 vs 20%; P = 0.10), and longer flaccid (64.2 vs 0%; P < 0.05) and erect lengths (58.4 vs 33.3%; P = 0.06).

Table 2. Key outcomes from objective and standardized questionnaires at 9 months post-prostatectomy (after open-label phase).
Variable Group 1, n = 9: No PTT × 8 months* (No Tx) Group 2, n = 9: No PTT × 5 months, PTT × 3 months (No Tx → Tx) Group 3, n = 13: PTT × 5 months, No PTT × 3 months (Tx → No Tx) Group 4, n = 14 PTT × 8 months (Tx) P value (No Tx vs Tx)
Objective assessments
Change in length, cm
To tip, mean (sd) 0.5 (1.5) 1.0 (1.6) 1.0 (1.7) 1.7 (0.9) <0.05
To tip, % (sd) 3.3 (9.5) 7.2 (11.3) 7.2 (12.4) 11.3 (7.0) <0.05
To corona, mean (sd) −0.1 (1.6) 0.5 (1.8) 1.8 (1.6) 1.7 (0.8) <0.01
To corona, % (sd) −0.4 (11.3) 5.2 (13.8) 16.8 (14.3) 14.7 (8.2) <0.01
Use of PDE5 inhibitors over past 6 months, % 86 88 89 79 0.69
Use of ICIs over past 6 months, % 86 38 70 14 <0.01
Average daily device use over 8 months, min 1.5 15.4 18.1 33.4 <0.0001
Standardized questionnaires
Change in IIEF, negative denotes loss of function, median change from baseline (IQR)
EF domain (all-comers) −8 (−18, −4) −6 (−14, 5) 0 (−9, 1) −1 (−14.5, 7) 0.16
EF domain (baseline no ED) −11 (−22.5, −2.5) −5 (−7.5, 2.8) −3.5 (−16.5, 1) −2.5 (−7.5, 1.5) 0.31
EF domain (baseline ED) −8 (−10, −6) −8 (−23, 5.5) 0.5 (−1.5, 7.8) 0 (−25, 19) 0.77
Orgasmic function domain −3 (−4, 0) −1.5 (−4.8, 0) −3.5 (−5, 0) −1 (−6.5, 3.5) 0.90
Sexual desire domain −1 (−1, 0) 0 (−2.5, 2) 0 (−0.3, 0) 0 (−1, 2.5) 0.13
Intercourse satisfaction domain −3 (−4, −2) −2 (−5.5, 1) 0 (−3, 0) −1 (−6, 4.5) 0.25
Overall satisfaction domain −2 (−4.3, 0) 0 (−3.5, 3) 0 (−3, 0) 0 (−4, 1) 0.24
SEP Q2, % 50 56 78 100 <0.01
SEP Q3, % 33 56 67 100 <0.01
Additional subjective responses
Has the treatment improved your erectile function, % 29 44 63 57 0.21
Has the treatment improved your ability to engage in sexual activity, % 29 33 63 50 0.34
Satisfaction with sexual function, %
Very satisfied 0 11 20 43 0.06
Somewhat satisfied 14 33 10 21
Neutral 29 0 20 7
Somewhat dissatisfied 0 22 30 7
Very dissatisfied 57 33 20 21
Satisfaction with penile length, %
Very satisfied 14 22 30 57 <0.05
Somewhat satisfied 0 33 30 21
Neutral 43 22 20 7
Somewhat dissatisfied 29 22 20 14
Very dissatisfied 14 0 0 0
Improvement in length, %
Yes 20 78 60 71 0.10
No 60 11 30 14
Worse 20 11 10 14
Estimated percent improvement in length, median (IQR) 0 (0, 18.8) 8.5 (5, 17.5) 10 (6.3, 21.3) 15 (10.0, 20.0) 0.16
How does your FLACCID length compare with that prior to surgery, %
Much shorter 29 0 0 7 <0.05
Slightly shorter 43 22 40 14
Same 29 11 40 14
Slightly longer 0 67 20 57
Much longer 0 0 0 7
How does your ERECT length compare with prior to surgery, %
Much shorter 33 0 14 17 0.06
Slightly shorter 33 38 14 0
Same 0 0 29 25
Slightly longer 33 50 43 42
Much longer 0 13 0 17
Has the therapy overall resulted in a meaningful improvement, % Yes 40 78 90 86 0.05
De novo penile curvature, % 14 0 10 0 0.13
De novo penile pain, % 0 0 10 0 NA
Satisfaction with RestoreX (scale 1–10, 10 = extremely satisfied), median (IQR) 8 (7.3, 8) 8 (6.5, 8.5) 7.5 (5.8, 9) 8.5 (8, 10) 0.09
Comfort with RestoreX (scale 1–10, 10 = most comfortable), median (IQR) 4 (3, 6.3) 7 (5.5, 8.5) 6 (4.8, 7.5) 8 (5.8, 8) <0.01
Would recommend RestoreX to friend, %
Recommend 86 89 90 100 <0.05
Indifferent 14 11 10 0
Discourage 0 0 0 0
If starting over, would choose to use RestoreX post-prostatectomy, %
Yes 71 89 80 100 <0.01
Unsure 29 0 20 0
No 0 11 0 0
  • All results represent 9-month outcomes minus baseline. Analysis of covariance used to detect significance for length and IIEF score, Wilcoxon tests utilized for continuous, skewed data, Student's t-tests for continuous, normally distributed data, Fisher's exact tests for categorical variables, and likelihood ratio if single cells <5.
  • EF, erectile function; ICI, intracavernosal injections; IIEF, International Index of Erectile Function; IQR, interquartile range; PDE5, phosphodiesterase-5 inhibitor; PTT, penile traction therapy; SD, standard deviation; SEP, sexual encounter profile; Tx, treatment.
  • * The No Tx group includes men who were originally in the control group and then elected to use the device <15 min daily during the open-label phase.
  • Number of participants varies within each group by variable; missing data points were not replaced/imputed.
  • Values used in this table for the IIEF were obtained by subtracting baseline from 6-month values. In contrast, values in Fig. 2 were obtained using the median result from the groups at baseline and 6 months.
Details are in the caption following the image
Changes in penile length (A), and IIEF-EFD scores compared to baseline (B and C). Panel B represents changes from baseline for each grouping (e.g., Group A cohort at 9 months minus baseline), whereas Panel C represents changes within each individual and then grouped by cohort (e.g., individual 9 month data minus baseline). This provides two different methods of analyzing the data to confirm findings. P-values represent comparisons between the NoTx and Tx Groups (Group 1 vs Group 4).

Regarding erectile function, men treated with RxPTT × 8 months reported lower PDE5 inhibitor (78.6 vs 85.7%; P = 0.69) and ICI use (14.3 vs 85.7%; P < 0.01) over the past 6 months compared to the no treatment arm. Men who chose treatment also demonstrated lesser impacts of prostatectomy in all domains of the IIEF, including the erectile function domain (IIEF-EF score −1 vs −8; P = 0.16), regardless of baseline erectile status. Responses to the sexual encounter profile (SEP) Question 2 (ability to achieve an erection) and Question 3 (ability to maintain an erection) also reflected better outcomes among men who chose treatment (100% vs 50% and 100% vs 33.3%; P < 0.01 for both). Subjectively, men who chose treatment also reported higher rates of improved erectile function (57.1 vs 28.6%; P = 0.21), ability to engage in sexual activity (50.0 vs 28.6%; P = 0.34), and overall satisfaction with sexual function (64.3 vs 14.3%; P = 0.06).

Group 2 (Crossover from No Treatment × 5 Months to RxPTT × 3 Months)

Men who crossed over from no treatment to treatment experienced some degree of length increase (+0.5 cm), but this increase was notably lower than those who had begun treatment at 1 month postoperatively (+1.7 cm). Similarly, compared to men who chose no treatment throughout both the randomized and open-label phases (Group 1), men in this crossover group experienced lesser impacts on IIEF-EF score (−6 vs −8; P = 0.46), but not to the same extent as men who initiated treatment at 1 month postoperatively (Group 3 = 0, Group 4 = −1). SEP Questions 2 and 3 were also reflective of some degree of catch-up (55.6% for Group 2 vs 50% Group 1, P = 0.83 and 55.6 Group 2 vs 33.3 Group 1, P = 0.39) but not to the same extent as men treated at 1 month postoperatively. Other measures of subjective changes to erectile function and length were also partially better in this crossover group than in the no treatment group but not as improved/preserved as in the men who began treatment at 1 month, with few exceptions.

Group 3 (Crossover from RxPTT × 5 Months to Limited/No Treatment × 3 Months)

Men who crossed over from treatment to no treatment experienced preserved penile length improvements compared to those who used treatment for the full 8 months (+1.8 vs +1.7 cm). Similarly, IIEF-EF scores remained improved compared to men who continued treatment (IIEF-EF score 0 vs −1; P = 0.85). Other subjective and standardized assessments also demonstrated improved erectile function compared to Groups 1 and 2 and either similarity or slight decreases compared to Group 4. Results overall suggest that treatment initiated at 1 month postoperatively was superior to either no treatment or initiating treatment at 6 months postoperatively. Additionally, findings suggest a durable response, despite discontinuing treatment.

Groups 1 and 2 (No Early RxPTT Use) vs Groups 3 and 4 (Early RxPTT Use)

To evaluate whether improvements in length and erectile function were secondary to early (1 month postoperatively) vs late (6 months postoperatively) initiation of treatment a regression analysis was performed using early vs delayed and 10-h increments in total device use (total duration of RxPTT use) as analysed variables. Results demonstrated that early vs delayed therapy was more likely to account for the difference observed in penile length (parameter estimate 0.9 cm, 95% CI 0.3, 1.4; P < 0.01), while total duration of RxPTT use as a variable was not predictive of outcomes. In contrast, for erectile function, the total duration of RxPTT use demonstrated significant improvements (parameter estimate +1 point on the IIEF-EF for every 10 h of use, 95% CI 0.2, 1.9; P = 0.02), while early vs delayed treatment failed to achieve statistical significance, possibly due to a small effect size and limited sample (PE +1.1 IIEF-EF [95% CI −3.9, 6.0] for early vs delayed therapy [P = 0.66]). Results overall would suggest that both total duration of RxPTT use and early onset of treatment are likely independent predictors for achieving optimal outcomes, confirming findings from analyses presented earlier in the manuscript.

Other Subjective Findings

The majority of men who performed treatment >15 min/day during some portion of their postoperative course reported that the therapy was meaningful (78–90%). Men in all groups also rated their overall satisfaction with treatment at 7.5–8.5 out of 10, even those who elected to utilize the treatment in a limited fashion (i.e., Group 1). Interestingly, those who reported lower overall comfort with the device were less likely to utilize the device (Group 1, 4/10 vs Group 4, 8/10; P < 0.01). The majority of men in all groups reported that they would recommend the therapy to a friend (86–100%) and would choose to use the therapy again if given the chance post-prostatectomy (71–100%; both measures highest in Group 4 and lowest in Group 1; P < 0.01).

Adverse Events

Adverse events (AEs) are detailed in Table 3. In general, there were no significant AEs, with all symptoms being mild and transient upon device discontinuation. The most common AE was temporary glanular erythema/discolouration in approximately 36% who used the device regularly, followed by discomfort in 14% and abnormal sensation in 4%. One patient in the open-label phase chose to discontinue therapy due to multiple concerns, including fear and anxiety about stretching the penis in the setting of concurrent stress urinary incontinence and pelvic floor spasms, decreased sensation, and discomfort with use. No other study participants discontinued use due to AEs. Notably, one patient slept with the device intact and reported no AEs related to device use.

Table 3. Adverse events at 9 months post-prostatectomy (after open-label phase).
Symptom No PTT, n = 39 Avg <15 min/day, PTT n = 15 Avg ≥15 min/day PTT, n = 28 Total PTT, N = 43
Self-reported as related to device *
Glanular erythema/discolouration, n (%) 0 0 35.7 23.2
Discomfort, n (%) 0 13.3 14.3 14.0
Decreased/abnormal sensation, n (%) 0 6.7 3.6 4.7
Self-reported as unrelated to device
Pain, n (%) 0 0 3.6 2.3
  • * Note, one patient reported discontinuing traction after 1 week (open-label phase) due to discomfort, decreased sensation, and fear/anxiety of stretching the penis in the setting of postoperative stress urinary incontinence and pelvic floor spasms. A second notable patient reported falling asleep with the device intact without any adverse events. All other symptoms reported above were transient and did not result in device discontinuation.

Discussion

The findings of this study are consistent with and provide further support for outcomes previously reported from the randomized phase [4]. Specifically, men treated with RxPTT experienced greater length improvements and preservation of sexual function compared to untreated men. Interestingly, men who crossed over from no treatment to treatment at 6 months (Group 2) experienced some degree of catch-up with penile length and sexual function, however, improvements were notably smaller than in those who began treatment at 1 month postoperatively. Although the exact reason for this difference in outcomes with delayed treatment compared to earlier treatment is unclear, it may relate to a limited therapeutic window in which erectile function can be preserved post-prostatectomy and to progressive cavernosal fibrosis, which has been previously reported [15]. Conversely, those who limited/stopped treatment at 6 months (Group 3) experienced preservation of length and erectile function, despite discontinuing treatment. And those who consistently performed treatments during the full 8-month time period were found to have either similar improvements to those in Group 3 or slightly better outcomes on standardized and non-standardized subjective questionnaires, with few exceptions. Overall, results highlight the importance of beginning therapy early postoperatively to achieve optimal outcomes.

The current study is notable in that it represents the first treatment ever shown, in an RCT, to preserve erectile function post-prostatectomy, with benefits maintained after therapy discontinuation. Specifically, prior RCTs evaluating PDE5 inhibitors as well as the use of vacuum erection devices have all failed to demonstrate persistent benefits following therapy discontinuation (washout) [2, 5-7]. If externally validated, this is significant as it arguably represents the most notable advancement in post-prostatectomy ‘penile rehabilitation’ (i.e., length and function) since the introduction/popularization of nerve-sparing techniques [16].

The proposed mechanism for improvement in erectile function with RxPTT may relate to tensile-force-mediated nitric oxide release and through activation of the PKA/Akt pathways [17]. This hypothesis is supported by upregulation of nitric oxide synthase in vascular systems exposed to tensile forces, a finding which is notably maximally observed after 30 min of stretch [18]. Another potential mechanism for the observed beneficial effects of traction includes tissue remodelling via upregulation of matrix metalloproteinases [19]. However, given the relatively limited data available and novelty of the current findings, further studies are needed to better delineate underlying mechanisms.

This study has several important limitations, including a relatively small sample size and the single-centre enrolment. This limitation is particularly pronounced when reporting outcomes at the 9-month time point (dropouts) and after subdividing men into four groupings. As such, this study should be interpreted largely as confirming previously reported outcomes from the randomization phase and as providing new insights into the durability of response and limited ability to catch up with delayed treatment. The reason for fewer data points at 9 months is likely related to multiple factors, including travel restrictions from COVID-19, the tertiary nature of the host institution, limited incentives for patients to travel for assessments, and rigorous study requirements necessitating data capture within 1 month of study endpoints. The study also lacks a true viable sham treatment, and the principal investigator and the study centre are the developers of the RxPTT device. Despite these limitations, the study in general has several notable strengths, including its randomized controlled design, blinded measures obtained in duplicate (for penile length), inclusion of both objective measures and standardized questionnaires, and inclusion of all-comers post-prostatectomy with minimal exclusion criteria. It also represents one of only a few RCTs that have ever been completed evaluating sexual function and penile rehabilitation post-prostatectomy.

In conclusion, this study supports earlier findings that the use of RxPTT beginning at 1 month post-prostatectomy improves penile length and helps preserve erectile function. Although limited, the crossover data suggest persistent improvements after treatment discontinuation, which, if confirmed, would represent the first therapy ever shown to preserve erectile function outside of nerve-sparing techniques. Based on limited data, men who initiated therapy in a delayed manner (i.e., at 6 months) did not experience similar benefits to those who began treatment earlier. External validation in a larger, multicentre series is currently ongoing (NCT05244486).

Acknowledgements

This study was an investigator-initiated trial and was conducted using internal Mayo Clinic funds. Traction devices were provided by PathRight Medical at no charge.

    Disclosure of Interests

    This study was performed using internal Mayo Clinic funding, with Restorex devices provided by PathRight Medical at no charge. Dr Landon Trost is the inventor of the Restorex traction device, and the Mayo Clinic maintains the licensing rights to the technology. Both the Mayo Clinic and Landon Trost have financial interests related to the device. This conflict has been reviewed by the Mayo Clinic Institutional Review Board and was felt to not preclude involvement by either Landon Trost or the Mayo Clinic in the study.

    Abbreviations

  1. ED
  2. erectile dysfunction
  3. ICI
  4. intracavernosal injection
  5. IIEF
  6. International Index of Erectile Function
  7. PDE5
  8. phosphodiesterase-5
  9. PTT
  10. penile traction therapy
  11. RCT
  12. randomized controlled trial
  13. RxPTT
  14. Restorex penile traction therapy