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. 2021 Jan 16;6(3):100647. doi: 10.1016/j.adro.2021.100647

Successful Use of Absorbable Hydrogel Rectal Spacers (SpaceOAR) Before Salvage Radiation Therapy After Previous Prostate Cryotherapy

James Applewhite a, Jerry Barker Jr b,∗, James C Vestal c
PMCID: PMC7966841  PMID: 33748548

Introduction

Cryotherapy is a minimally invasive procedure used to treat localized prostate cancer with low surgical risk1 and acceptable morbidity2 in selected patients.3 For some patients, particularly those diagnosed with higher risk disease, local recurrence can occur after cryoablation.4,5 Salvage radiation therapy has been shown to be an effective treatment in these cases.6

Although radiation therapy (RT) is widely accepted as an effective treatment for prostate cancer, the rectum, owing to its anatomic proximity, is a dose-limiting structure.7 Various injectable agents have been inserted as spacing materials into the space between the prostate and rectum to reduce rectal dose during prostate radiation.8 Absorbable hydrogel rectal spacer (SpaceOAR) is a widely studied injectable polyethylene glycol hydrogel that shifts the anterior rectal wall away from the prostate9 and maintains adequate space for approximately 3 months and is completely absorbed in 6 months.10 Because of its simple application procedure and low rate of complications11 as well as its proven efficacy in reducing rectal radiation dose and long-term toxicity,7 SpaceOAR application is a Food and Drug Administration–cleared procedure before prostate RT.

Prostate cryoablation uses continuous transrectal ultrasound guidance to insert cryoneedles transperineally into the prostate. Argon and helium gases are used for cooling and warming, respectively.12 Real-time ultrasound gives visualization of ice-ball formation,3 and freezing/thawing cycles are repeated as needed to cover the target. Various techniques aim to adequately freeze/destroy malignant tissue while protecting normal tissues (eg, warming urethral catheter, warm saline rinses to anterior rectal wall). However, whole gland cryoablation results in universal erectile dysfunction,3 suggesting some extraprostatic tissue damage. Presumably for this reason, some physicians have expressed concerns about whether absorbable hydrogel spacers could be safely and effectively used in patients who have been previously treated with cryosurgery.13,14 Herein we present the first reported cases where absorbable hydrogel spacers were successfully used after previous prostate cryotherapy.

SpaceOAR Technique

SpaceOAR is introduced into the potential space between the rectum and prostate using transperineal technique. With the patient in the dorsal lithotomy position, the perineum is cleaned and anesthetized using local anesthesia. Under continuous transrectal ultrasound guidance, a needle is introduced into the space between prostate and rectum and injectable sterile saline is used to hydrodissect that space. Two solutions (a trilysine buffer/polyethylene glycol solution and a salt buffer accelerant solution) are then mixed together via a Y-connector and simultaneously injected into the established space via an 18-gauge needle. When mixed, the solutions cross link to form a solid hydrogel within seconds. This hydrogel spacer persists for approximately 3 months and then gradually liquefies via hydrolysis.

Case Reports

Case 1

A 73-year-old man originally presented with a screening prostate specific antigen (PSA) of 5.99 ng/mL. Transrectal ultrasound-guided needle biopsy of the prostate revealed a Gleason 7 (4 + 3) adenocarcinoma involving 1 of 12 cores from the left mid apex. Staging studies demonstrated nonmetastatic disease. The patient elected to have treatment with definitive cryotherapy. PSA levels decreased to 0.4 ng/mL 1 month after cryoablation. However, 8 months later his PSA increased to 2.1 ng/mL. A restaging magnetic resonance imaging (MRI) scan demonstrated a PI-RADS 4 lesion involving the bilateral anterior apex to the mid of the peripheral gland. An MRI-fusion prostate biopsy was performed, showing Gleason 6 (3 + 3) adenocarcinoma in 2 cores (RMA is a biopsy from the right medial apex of the prostate gland. LMA is a biopsy from the left medial apex of the prostate gland) and Gleason 7 (3 + 4) adenocarcinoma in the lesion-directed biopsy. The patient elected to pursue salvage radiation therapy. Before the start of radiation therapy, an absorbable hydrogel spacer was surgically placed. There was no technical challenge in delivering the spacer between the prostatic fascia and the rectum, and postprocedure MRI demonstrated excellent hydrogel spacer placement (Fig. 1). He was then treated with cone beam computed tomography (CT) image guided intensity modulated radiation therapy to a total dose of 7920 cGy in 44 fractions, which he tolerated without complication.

Figure 1.

Figure 1

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(A) Axial MRI image demonstrating absorbable hydrogel spacer (SpaceOAR) situated between rectum and prostate/seminal vesicles (Case 1). (B) Sagittal MRI image demonstrating absorbable hydrogel spacer (SpaceOAR) situated between rectum and prostate/seminal vesicles (Case 1).

Case 2

A 72-year-man initially presented with a screening PSA of 5.8 ng/mL. Transrectal ultrasound-guided needle biopsy of the prostate demonstrated Gleason 7 (3 + 4) adenocarcinoma in 1 of 12 cores, Gleason 6 (3 + 3) adenocarcinoma in 2 of 12 cores, and a small focus of atypical glands in 1 of 12 cores. Initial staging studies demonstrated nonmetastatic disease. The patient elected to have definitive treatment using cryoablation. His PSA nadir was 4 months posttreatment at 1.28 ng/mL. During the next 15 months, his PSA slowly increased to as high as 6.0 ng/mL. A restaging Axumin positron emission tomography/CT scan demonstrated uptake in the prostate gland, but without evidence of metastatic disease. The patient elected to pursue salvage radiation therapy. An absorbable hydrogel spacer (SpaceOAR) was surgically placed before the start of salvage radiation therapy. There was no technical challenge in delivering the spacer between the prostatic fascia and the rectum, and postprocedure MRI demonstrated excellent hydrogel spacer placement (Fig. 2). He was then treated with cone beam CT image guided intensity modulated radiation therapy to a total dose of 7920 cGy in 44 fractions, which he tolerated without complication.

Figure 2.

Figure 2

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(A) Axial MRI image demonstrating absorbable hydrogel spacer (SpaceOAR) situated between rectum and prostate/seminal vesicles (Case 2). (B) Sagittal MRI image demonstrating absorbable hydrogel spacer (SpaceOAR) situated between rectum and prostate/seminal vesicles (Case 2).

Discussion

Prostate cryoablation is a localized treatment option for selected patients with localized prostate cancer.3,15,16 Some patients develop locally recurrent disease after definitive cryoablation6 and are often candidates for additional local treatment with curative intent. Although some patients can be treated with repeat courses of salvage cryotherapy,17 additional local treatment using conformal external beam radiation therapy has also been used successfully.

External beam radiation therapy for prostate cancer requires that ablative radiation doses18 be applied to a treatment volume situated immediately adjacent to the dose-limiting rectum.19, 20, 21 Modern highly conformal radiation therapy techniques have been successfully used to reduce the risk of rectal toxicity while delivering tumoricidal doses to the prostate gland.20 In addition, over the last several years the use of absorbable hydrogel spacers (eg, SpaceOAR) have been used to further improve the therapeutic window.22 These hydrogel spacers have been demonstrated to consistently reduce rectal doses10, 11 (>90% patients achieving reduction in rectal V70 of at least 25% in a randomized trial11) and improve quality of life23,24 with little toxicity (rate of grade 1 or greater rectal acute adverse events or procedure adverse events through 6 months similar to the control group in a randomized trial11) for men receiving high-dose radiation therapy for prostate cancer, and these spacers have achieved Food and Drug Administration clearance and widespread acceptance.

Successful transperineal instillation of absorbable hydrogel spacers requires the use of injectable sterile saline to hydrodissect the space between prostate and rectum before hydrogel is injected. Some authors have raised concerns that previous prostate cancer treatment (eg, cryotherapy, high-intensity focused ultrasound) may prevent successful dissection of this space, resulting in suboptimal spacer placement or procedural complication.13, 14 However, previous reports have described successful use of hydrogel spacers after previous prostatectomy, external beam radiation therapy, and high-intensity focused ultrasound.6, 16, 25 In this report, we have shown that absorbable hydrogel spacers can also be effectively used in patients previously treated with prostate cryoablation, without periprocedural complication.

Conclusions

We have demonstrated the feasibility of using SpaceOAR before salvage RT after previous prostate cryoablation. Our ongoing work is evaluating the dosimetric benefits of spacers in this setting. In addition, we will continue to evaluate additional similar cases, seeking to identify selection criteria for optimal candidates for hydrogel placement before salvage radiation therapy.

Absorbable hydrogel spacers can be safely and effectively used before salvage radiation therapy for selected patients who have been previously treated with prostate cryoablation.

Footnotes

Sources of support: This work had no specific funding.

Disclosures: none.

Data Sharing Statement: Research data are stored in an institutional repository and will be shared upon request to the corresponding author.

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