Change in prostate volume reduction and symptomatic improvement in men treated with Rezūm convective water vapour thermal thera

doi:10.21203/rs.3.rs-2122043/v1

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Change in prostate volume reduction and symptomatic improvement in men treated with Rezūm convective water vapour thermal thera

https://doi.org/10.21203/rs.3.rs-2122043/v1

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Background: Rezūm convective water vapour thermal therapy is a minimally invasive, office-based treatment for benign prostatic hyperplasia (BPH). While studies have demonstrated its efficacy in symptomatic improvement, its effect on objective measures such as prostate volume (PV) reduction is poorly characterized. The purpose of this study was to evaluate the change in PV and its relationship to improvement in symptom scores following Rezūm therapy.

Methods: Quality of life outcomes and PV were assessed at baseline and 12 months post-procedure. The percent change from baseline in outcomes and PV were calculated for each patient, as was the injection to baseline volume ratio. The association between the total number of vapour injections and changes in outcomes and PV were evaluated using linear regression models.

Results: A total of 49 patients (mean age = 67.8; standard deviation [SD] = 9.4) underwent the procedure between April 2019 and September 2020, with a median baseline PV of 71.5 and median number of vapour injections of 11.0. At 12 months, the median percent change in prostate volume was -34.0% (interquartile range: -49.2%, -16.7%), with 45/49 (91.8%) patients having reduced volume. Among the 45 patients with reduced volume at 12 months, every 10% increase in volume reduction was associated with a 7.5% (95% confidence interval, 1.4% to 13.6%; p=0.02) improvement in the International Prostate Symptom Score. There was no significant association between the total number of injections or injection to baseline volume ratio and change in PV.

Conclusions: In this cohort of patients treated with Rezūm convective water vapour thermal therapy for BPH, it was demonstrated that there is a correlation between greater PV reduction and greater symptomatic improvement. Additionally, this study showed no association between more injections or the ratio of injections to prostate volume changes, refuting the claim that more injections are better.

Prostatic hyperplasia

Lower urinary tract symptoms

Male

Prospective study

Benign prostatic hyperplasia (BPH) is a urologic condition characterized by a progressive increase in prostate size.^1,2 Patients with BPH will often develop lower urinary tract symptoms (LUTS), and it has been found that healthcare costs attributed to BPH are among the top 10 most prominent and costly diseases in men older than 50 years.^3,4 Urinary retention is one of the most significant complications of BPH and, historically, it has represented an indication for surgery.^5–7 From a socioeconomic perspective, patients with urinary retention present a particular challenge, as, in addition to recovery or surgery, these patients have the inability to urinate and increasing pain, and will eventually require an emergency room visit, catherization, long-term physician follow-up, and an attempt at catheter removal.⁶

In recent years, a novel, minimally-invasive procedure was introduced for the management of BPH, the Rezūm System (Boston Scientific Company Inc., Marlborough, MA, USA), which uses convective radiofrequency water vapor thermal energy to ablate obstructing prostate tissue.^1,4 A retractable needle is injected into the lateral or median lobes and water vapor is delivered at a temperature of 103 degrees Celsius; the needle can be administered to multiple treatment sites as needed.⁴ The Rezūm System was approved by the Food and Drug Administration (FDA) in 2015 based on the results of the pivotal randomized trial (NCT01912339), which demonstrated that Rezūm therapy provides rapid and durable improvements in BPH symptoms relative to controls.^4,8 Support for Rezūm therapy was also published by the National Institute for Health and Care Excellence (NICE) in June 2020.^9,10 Additionally, both the American Urological Association (AUA) and Canadian Urological Association (CUA) have now included water vapor thermal therapy in their most recent guidelines as a treatment that may be offered to some BPH patients.^1,11,12 Clinical evidence, including real-world data, have demonstrated the efficacy and safety of Rezūm therapy across a range of different BPH subgroups (e.g., large glands, urinary retention, or median lobe involvement).^5,13−20

BPH progression and its negative outcomes have been shown to be related to baseline prostate volume (PV), which can be predictive of treatment response; disease progression includes worsening of BPH symptoms and quality of life and the need for surgery.^21–23 Prior research using diagnostic imaging has demonstrated reductions in prostate volume following Rezūm therapy, though evidence on this topic is lacking and further studies are needed.²⁴ Additionally, there is currently no consensus on the optimal number of injections required during the Rezūm procedure.²⁵ Up to 15 injections can be administered with each device and the number of injections given may vary based on the anatomy of the patient. Guidance on injection frequency is available, but, ultimately, this decision is at the discretion of the treating physician.^25,26 Determining the ideal number of injections will ensure that patients achieve adequate symptomatic relief while limiting the risk of treatment-related adverse events and healthcare resource use. The purpose of this study was to evaluate the change in PV and its relationship to improvement in symptoms scores following Rezūm therapy, as well as the association between the number of vapour injections and changes in outcomes and PV.

Study subjects

A prospective registry was established in Canada at two high-volume centers, the University Health Network in Toronto, Ontario and the University of Montreal Hospital Center in Montréal, Québec, to follow BPH patients receiving Rezūm therapy at these institutions.

Treatment procedure

Rezūm water vapour therapy was performed as previously described.^4,24,27 This system includes a generator containing a radiofrequency power supply, system controls, and a single-use transurethral delivery device that incorporates a standard 4 mm, 30-degree endoscopic cystoscopy lens. Water vapor thermal energy, created by the radiofrequency current against an inductive coil heater in the device handle, is delivered via a retractable needle and saline flush. The water vapor is delivered for 9 seconds, retracted, and then administered to another treatment site at the surgeon’s discretion. The goal is to create contiguous, overlapping lesions running parallel to the natural slope of the urethra. The intervention is customized to the shape and location of the gland, including treatment of the median lobe.

Assessments

All patients had baseline medical and BPH history documented. Patients completed the following validated questionnaires at baseline and 12 months following the procedure:

The International Prostate Symptom Score (IPSS)²⁸
The International Index of Erectile Function (IIEF-15)²⁹
The Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD) function and bother domains³⁰

PV was also measured at baseline and at 12 months using transrectal ultrasound and standard ellipsoid formula calculation.

Statistical methods

Patient demographics and treatment characteristics were summarized using descriptive statistics. The percent reduction from baseline to 12 months in PV, and percent change in functional outcomes (IIEF-15, IPSS, MSHQ-EjD Function and Bother) were calculated for patients with non-missing data at baseline and 12 months. The relationship between the total number of injections and percent reduction in PV, and the injection to baseline volume ratio and percent reduction in PV were quantified using linear regression models and visualized using scatterplots. Injection to baseline volume ratio was divided by 100 for the regression analysis. The relationships between percent reduction in PV and percent improvement in functional outcomes were analyzed in the same manner. Statistical analyses were conducted using R version 4.0.0, and p-values less than 0.05 were considered statistically significant.

Baseline characteristics & 12-month outcomes

A total of 49 men underwent the procedure between April 2019 and September 2020 with a median (interquartile range [IQR]) age of 67.4 (60.6, 72.2) years, prostate specific antigen of 3.5 (1.7, 5.4) ng/mL, peak urinary flow (QMax) of 7.5 (4.0, 10.0) mL/second, post-void residual volume of 114 (36, 297) mL, PV of 71.5 (51.0, 95.0) cc, and 11 (8, 13) total injections (Table 1).

Table 1

Baseline characteristics (49 subjects)
Characteristic
Age
Mean (SD)	67.8 (9.4)
Median (Q1, Q3; Min, Max)	67.4 (60.6, 72.2; 50.9, 100.7)
Prostate specific antigen, ng/mL
Mean (SD)	4.9 (5.0)
Median (Q1, Q3; Min, Max)	3.5 (1.7, 5.4; 0.5, 26.9)
Prostate volume, cc
Mean (SD)	73.2 (27.9)
Median (Q1, Q3; Min, Max)	71.5 (51.0, 95.0; 24, 150)
Peak urinary flow (QMax), mL/sec
Mean (SD)	7.4 (4.3)
Median (Q1, Q3; Min, Max)	7.5 (4.0, 10.0; 0.5, 19.0)
Post-void residual volume, mL
Mean (SD)	175.7 (166.4)
Median (Q1, Q3; Min, Max)	114 (36, 297; 0, 580)
IPSS
Mean (SD)	21.7 (6.7)
Median (Q1, Q3; Min, Max)	22 (18, 26; 6, 31)
IPSS QoL
Mean (SD)	4.5 (1.0)
Median (Q1, Q3; Min, Max)	5 (4, 5; 2, 6)
IIEF
Mean (SD)	49.6 (16.1)
Median (Q1, Q3; Min, Max)	50.5 (38.5, 66.0; 15, 71)
MSHQ-EjD Bother
Mean (SD)	2.4 (1.6)
Median (Q1, Q3; Min, Max)	3 (2, 3; 0, 5)
MSHQ-EjD Function
Mean (SD)	8.6 (4.0)
Median (Q1, Q3; Min, Max)	9 (6, 11; 1, 15)
Number of vapour injections - Right
Mean (SD)	4.6 (1.7)
Median (Q1, Q3; Min, Max)	4 (3, 5; 2, 11)
Number of vapour injections - Left
Mean (SD)	4.5 (1.4)
Median (Q1, Q3; Min, Max)	5 (3, 5; 2, 9)
Number of vapour injections - Median lobe
Mean (SD)	1.7 (1.5)
Median (Q1, Q3; Min, Max)	1 (0, 3; 0, 5)
Number of vapour injections - Center no median lobe
Mean (SD)	0.2 (0.6)
Median (Q1, Q3; Min, Max)	0 (0, 0; 0, 3)
Total number of vapour injections
Mean (SD)	11.0 (3.5)
Median (Q1, Q3; Min, Max)	11 (8, 13; 4, 21)
IIEF, International Index of Erectile Function; IPSS, International Prostate Symptom Score; Max, maximum; Min, minimum; MSHQ-EjD, Male Sexual Health Questionnaire for Ejaculatory Dysfunction; Q1, quartile 1; Q3, quartile 3; QoL, quality of life; SD, standard deviation.

Median changes from baseline to 12 months across functional outcome measures are presented in Table 2. The median PV at 12 months was 43 (IQR: 32, 65) cc and the median percent change in PV was − 34.0% (IQR: -49.2%, -16.7%), with 45/49 (91.8%) patients overall having reduced PV.

Table 2

Functional outcomes at 12 months
Outcome	12 months
	Absolute	Change from baseline
Peak urinary flow (QMax), mL/sec (n = 3)	23.0 (20.4, 27.0)	13.0 (8.3, 17.0)
Post-void residual volume, mL (n = 25)	54 (11, 145)	-84 (-243, 0)
IPSS (n = 30)	7 (3, 13.2)	-16 (-20, -9)
IPSS QoL (n = 30)	1 (0, 3)	-3 (-4, -2)
IIEF (n = 19)	56.0 (39.5, 68.5)	1.0 (-4.5, 4.8)
MSHQ-EjD Bother (n = 22)	1.5 (0, 3)	0 (0, 0)
MSHQ-EjD Function (n = 22)	8.5 (3.5, 12.8)	-0.5 (-3.2, 0.5)
Values are presented as median (Q1, Q3)
IIEF, International Index of Erectile Function; IPSS, International Prostate Symptom Score; MSHQ-EjD, Male Sexual Health Questionnaire for Ejaculatory Dysfunction; Q1, quartile 1; Q3, quartile 3; QoL, quality of life

PV and number of injections

Figure 1 displays the relationship between the total number of injections, injection to baseline PV ratio, and percent reduction in prostate volume. The association between the total number of injections and percent reduction in PV (Fig. 1A, 0.92, 95% confidence interval [CI]: -1.52 to 3.37, p = 0.45), and injection to baseline PV ratio and percent reduction in PV (Fig. 1B, -0.21, 95% CI: -2.19 to 1.76, p = 0.83) were not statistically significant.

PV and functional outcomes

Figure 2 displays the relationship between percent reduction in PV (restricted to patients who had a reduction in PV at 12 months) and percent improvement in functional outcomes. Reduction in PV was associated with a statistically significant increase in IPSS score improvement (Fig. 2A, 0.75, 95% CI: 0.14 to 1.36, p = 0.02). There was no statistically significant association seen for IIEF (Fig. 2B, -0.54, 95% CI: -1.21 to 0.13, p = 0.11), MSHQ-EjD Bother (Fig. 2C, -0.17, 95% CI: -2.74 to 2.40, p = 0.88), and MSHQ-EjD Function (Fig. 2D, 4.42, 95% CI: -3.06 to 11.9, p = 0.23).

Presently, there is limited evidence on the ideal number of injections administered during Rezūm therapy in patients with BPH. Additionally, it has been shown that there is a relationship between PV and treatment response in this patient population. The objective of this study was two-fold: 1) to evaluate the change in PV and its relationship to symptomatic improvement following treatment with Rezūm and 2) to determine if there is an association between the number of Rezūm injections and changes in outcomes and PV. A total of 49 patients were included in this analysis, who had a median number of injections of 11.0 and median percent change in PV from baseline to 12 months of -34.0%. Of these patients, 45 (91.8%) had reduced PV at 12 months; the remaining 4 patients had increases in PV of 3%, 7%, 38%, and 44%. Among the 45 patients with reduced PV, there was a statistically significant relationship between PV reduction and decreases in the IPSS, demonstrating that for every 10% increase in PV reduction, there was a 7.5% (95% CI, 1.4–13.6%; p = 0.02) improvement in the IPSS; however, there were no statistically significant associations between changes in PV and the other functional outcome measures (i.e., IIEF, MSHQ-EjD Bother, and MSHQ-EjD). The relationships between the total number of injections or injection to baseline volume ratio and changes in PV were also not statistically significant.

Changes in PV and functional outcome measures following Rezūm therapy in this study were consistent with prior studies on this procedure using the traditional injection technique.^4,10,24,31 Additionally, Aladesuru et al. published a retrospective cohort (52 men) in 2022 evaluating a “less is more” treatment approach with Rezūm therapy, consisting of a single water vapour injection per prostate lobe.²⁵ The authors found that this approach significantly improved IPSS scores (-11.63 points; p = 0.006) and QMax (5.36 mL/s; p = 0.008) at 12 months post-procedure. They concluded that this method is both safe and effective, and comparable to outcomes seen following the traditional approach of multiple injections based on baseline PV. Taken together with the results of the current study, such findings indicate that more Rezūm injections do not necessarily lead to greater symptom improvement.

The median change in PV in the current study was − 34.0%, and reduction in PV was significantly associated with IPSS score improvement. Earlier studies on this topic have demonstrated variable results.^32–38 Additional research in this area is needed to determine if certain clinical or patient characteristics may influence the relationship between PV and IPSS.

Despite its merits, this current study has some limitations. These include a small sample size coupled with no comparator intervention; thus, it is unclear how the Rezūm System performs against other treatment options. Secondly, as treatment allocation was known by both the patient and treating physician, outcomes assessment was unblinded. Though PV is an objective outcome, IPSS, IIEF-15, and MSHQ-EjD are patient-reported measures that are subject to bias when outcomes assessment is unblinded. Third, the number of paired values available for evaluation at 12 months was low due to patient dropout, missed follow-up, or missing data points; however, these patterns reflected what occurs in typical urology practice. A strength of this study was that it demonstrated that Rezūm therapy is effective in a real-world setting and results were consistent with prior published evidence on Rezūm. Additionally, improvements were shown to be maintained at long-term follow-up (i.e., 12 months). This study demonstrates that patients with BPH can achieve symptomatic relief with Rezūm therapy while reducing the risk of adverse events and healthcare resource use associated with more Rezūm injections.

In this cohort of patients treated with Rezūm convective water vapour thermal therapy for BPH, it was demonstrated that there is a correlation between greater PV reduction and greater symptomatic improvement. Additionally, this study showed no association between more injections or the ratio of injections to prostate volume changes, refuting the claim that more injections are better.

Conflicts of interest:

Drs. Elterman, Bhojani, Chughtai, Zorn are consultants for Boston Scientific.

Funding: None.

Arezki A, Sadri I, Couture F, et al. Reasons to go for Rezūm steam therapy: an effective and durable outpatient minimally invasive procedure. World J Urol. 2020.
Chughtai B, Forde JC, Thomas DD, et al. Benign prostatic hyperplasia. Nat Rev Dis Primers. 2016;2:16031.
Fenter TC, Naslund MJ, Shah MB, Eaddy MT, Black L. The cost of treating the 10 most prevalent diseases in men 50 years of age or older. Am J Manag Care. 2006;12(4 Suppl):S90-98.
McVary KT, Gange SN, Gittelman MC, et al. Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. J Urol. 2016;195(5):1529–1538.
McVary KT, Holland B, Beahrs JR. Water vapor thermal therapy to alleviate catheter-dependent urinary retention secondary to benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 2020;23(2):303–308.
Roehrborn CG. The epidemiology of acute urinary retention in benign prostatic hyperplasia. Rev Urol. 2001;3(4):187–192.
Wong A, Mahmalji W. The role of Rezūm ™ team ablation of the prostate in the treatment of patients with acute urinary retention secondary to benign prostatic hyperplasia. A single center, single surgeon case series and literature review. Aging Male. 2020;23(5):1620–1626.
Westwood J, Geraghty R, Jones P, Rai BP, Somani BK. Rezum: a new transurethral water vapour therapy for benign prostatic hyperplasia. Ther Adv Urol. 2018;10(11):327–333.
National Institute for Health and Care Excellence (NICE). Rezum for treating lower urinary tract symptoms secondary to benign prostatic hyperplasia. https://www.nice.org.uk/guidance/mtg49. Published 2020. Accessed May 5, 2021.
Johnston MJ, Noureldin M, Abdelmotagly Y, et al. Rezum water vapour therapy: promising early outcomes from the first UK series. BJU Int. 2020;126(5):557–558.
Parsons JK, Dahm P, Köhler TS, Lerner LB, Wilt TJ. Surgical Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA Guideline Amendment 2020. J Urol. 2020;204(4):799–804.
Nickel JC, Aaron L, Barkin J, Elterman D, Nachabé M, Zorn KC. Canadian Urological Association guideline on male lower urinary tract symptoms/benign prostatic hyperplasia (MLUTS/BPH): 2018 update. Can Urol Assoc J. 2018;12(10):303–312.
Babar M, Loloi J, Tang K, Syed U, Ciatto M. Emerging outcomes of water vapor thermal therapy (Rezum) in a broad range of patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia: A systematic review. Low Urin Tract Symptoms. 2022;14(3):140–154.
Bassily D, Wong V, Phillips JL, et al. Rezūm for retention-retrospective review of water vaporization therapy in the management of urinary retention in men with benign prostatic hyperplasia. Prostate. 2021;81(14):1049–1054.
Bole R, Gopalakrishna A, Kuang R, et al. Comparative Postoperative Outcomes of Rezūm Prostate Ablation in Patients with Large Versus Small Glands. J Endourol. 2020;34(7):778–781.
Elterman D, Bhojani N, Vannabouathong C, Chughtai B, Zorn KC. Rezūm therapy for ≥ 80-mL benign prostatic enlargement: a large, multicentre cohort study. BJU Int. 2022.
Elterman D, Bhojani N, Vannabouathong C, Chughtai B, Zorn KC. Large, Multi-Center, Prospective Registry of Rezūm Water Vapor Therapy for Benign Prostatic Hyperplasia. Urology. 2022;165:261–267.
Elterman DS, Bhojani N, Vannabouathong C, Chughtai B, Zorn KC. Rezūm water vapor therapy for catheter-dependent urinary retention: a real-world Canadian experience. Can J Urol. 2022;29(2):11075–11079.
Garden EB, Shukla D, Ravivarapu KT, et al. Rezum therapy for patients with large prostates (≥ 80 g): initial clinical experience and postoperative outcomes. World J Urol. 2021;39(8):3041–3048.
Ines M, Babar M, Singh S, Iqbal N, Ciatto M. Real-world evidence with The Rezūm System: A retrospective study and comparative analysis on the efficacy and safety of 12 month outcomes across a broad range of prostate volumes. Prostate. 2021;81(13):956–970.
Jeong YB, Kwon KS, Kim SD, Kim HJ. Effect of discontinuation of 5alpha-reductase inhibitors on prostate volume and symptoms in men with BPH: a prospective study. Urology. 2009;73(4):802–806.
Marberger MJ, Andersen JT, Nickel JC, et al. Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention. Combined experience from three large multinational placebo-controlled trials. Eur Urol. 2000;38(5):563–568.
Nickel JC. Benign prostatic hyperplasia: does prostate size matter? Rev Urol. 2003;5 Suppl 4(Suppl 4):S12-17.
Mynderse LA, Hanson D, Robb RA, et al. Rezūm System Water Vapor Treatment for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Validation of Convective Thermal Energy Transfer and Characterization With Magnetic Resonance Imaging and 3-Dimensional Renderings. Urology. 2015;86(1):122–127.
Aladesuru O, Amankwah K, Elterman D, et al. Pilot Study of "Less is More" Rezum for Treatment of BPH. Urology. 2022;165:256–260.
Green Z, Westwood J, Somani BK. What's New in Rezum: a Transurethral Water Vapour Therapy for BPH. Curr Urol Rep. 2019;20(7):39.
Dixon CM, Rijo Cedano E, Mynderse LA, Larson TR. Transurethral convective water vapor as a treatment for lower urinary tract symptomatology due to benign prostatic hyperplasia using the Rezūm(®) system: evaluation of acute ablative capabilities in the human prostate. Res Rep Urol. 2015;7:13–18.
28.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997;49(6):822–830.
Rosen RC, Catania JA, Althof SE, et al. Development and validation of four-item version of Male Sexual Health Questionnaire to assess ejaculatory dysfunction. Urology. 2007;69(5):805–809.
Alegorides C, Fourmarier M, Eghazarian C, Lebdai S, Chevrot A, Droupy S. Treatment of benign prostate hyperplasia using the Rezum® water vapor therapy system: Results at one year. Prog Urol. 2020;30(12):624–631.
Overland GB, Vatten L, Rhodes T, et al. Lower urinary tract symptoms, prostate volume and uroflow in norwegian community men. Eur Urol. 2001;39(1):36–41.
Franciosi M, Koff WJ, Rhoden EL. Correlation between the total volume, transitional zone volume of the prostate, transitional prostate zone index and lower urinary tract symptoms (LUTS). Int Urol Nephrol. 2007;39(3):871–877.
Kaplan SA, Reis RB, Staimen VB, Te AE. Is the ratio of transition zone to total prostate volume higher in African-American men than in their Caucasian or Hispanic counterparts? Br J Urol. 1998;82(6):804–807.
Agrawal CS, Chalise PR, Bhandari BB. Correlation of prostate volume with international prostate symptom score and quality of life in men with benign prostatic hyperplasia. Nepal Med Coll J. 2008;10(2):104–107.
Udeh EI, Ozoemena OF, Ogwuche E. The relationship between prostate volume and international prostate symptom score in Africans with benign prostatic hyperplasia. Niger J Med. 2012;21(3):290–295.
Awaisu M, Ahmed M, Lawal AT, et al. Correlation of prostate volume with severity of lower urinary tract symptoms as measured by international prostate symptoms score and maximum urine flow rate among patients with benign prostatic hyperplasia. African Journal of Urology. 2021;27(1):16.
Bosch JLHR, Hop WCJ, Kirkels WJ, Schröder FH. The International Prostate Symptom Score in a community-based sample of men between 55 and 74 years of age: prevalence and correlation of symptoms with age, prostate volume, flow rate and residual urine volume. British Journal of Urology. 1995;75(5):622–630.

Yes there is potential conflict of interest.

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Change in prostate volume reduction and symptomatic improvement in men treated with Rezūm convective water vapour thermal thera

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Version 1

Abstract

Figures

Introduction

Methods

Study subjects

Treatment procedure

Assessments

Statistical methods

Results

Baseline characteristics & 12-month outcomes

PV and number of injections

PV and functional outcomes

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1