A New Technique for Treating Low-risk Prostate Cancer—Super Active Surveillance

Summary

Overtreatment is often administered to patients with low-risk prostate cancer; super-active surveillance can help avoid such overtreatment.

Abstract

The treatment methods for patients with localized low-risk prostate cancer whose life expectancy is > 10 years mainly include radical prostatectomy, radiotherapy, active surveillance (AS), and focal therapy of low-risk prostate cancer. Research shows that only 3% of patients with low-risk prostate cancer experience disease progression or death, which indicates that there is overtreatment. The number of patients who choose active monitoring is increasing, but in the process of treatment, they often suffer great psychological pressure. Therefore, we are trying to adopt a more active treatment mode than active surveillance-Super Active Surveillance (Super-AS). Super-AS involves the application of ¹⁸F-PSMA PET/MR multimodal medical imaging, combined with real-time fusion of intraoperative transrectal ultrasound images, thereby enabling precise navigation for targeted argon-helium cryoablation therapy. The significance of Super-AS lies in its ability to effectively manage tumors in oncology while exerting minimal impact on functionality. Even if the focal therapy fails, the subsequent radical prostatectomy makes no significant difference in the overall oncological control, functional (urinary orifice and sexual function), and postoperative complications. Therefore, precise focal therapy can be an alternative transitional treatment for patients, from active monitoring to radical treatment, and it can also be seen as a "future bridge" for the treatment of localized prostate cancer. Consequently, Super-AS is a potentially promising therapeutic option for patients who meet the indications.

Introduction

Prostate cancer is the most common malignant tumor among male urinary system diseases, and with the widespread application of prostate-specific antigen (PSA) screening, the proportion of patients diagnosed with localized low-risk prostate cancer has been increasing year by year¹. The treatment methods for low-risk prostate cancer patients with a life expectancy greater than 10 years primarily include radical prostatectomy, radiotherapy, active surveillance (AS), and focal therapy². Radical prostatectomy and radiotherapy remain the primary methods for treating localized prostate cancer in China; however, the high incidence of postoperative complications leads some patients to refuse treatment due to fear and quality-of-life concerns. Although AS can avoid some complications and decline in quality of life associated with local treatments, patients still face the risks of elevated PSA levels and ongoing progression of Gleason scores, resulting in psychological anxiety³.

Currently, there is a lack of suitable treatment options for low-risk prostate cancer patients who refuse radical surgery and are concerned about the risk of progression after AS. Super-AS is a novel treatment involving the application of ¹⁸F-PSMA PET/MR multimodal medical imaging, combined with real-time fusion of intraoperative transrectal ultrasound images, thereby enabling precise navigation for targeted argon-helium cryoablation therapy. It combines the patient's health status and subjective willingness to implement a more proactive clinical approach to localized therapy. Super-AS not only alleviates the potential side effects associated with radical surgery and radiotherapy for patients but also reduces the psychological stress related to concerns about the risk of tumor progression. According to the pathological characteristics of prostate cancer, "Super-AS" can be considered as a treatment option for localized low-risk prostate cancer⁴. This study provides new ideas and evidence for the establishment of new treatment methods for low-risk prostate cancer by preliminarily exploring the effectiveness and feasibility of this treatment approach.

Protocol

The study has been reviewed by the Ethics Committee of the Civil Aviation General Hospital. Ethical statement. Written, informed consent was obtained from the patients.

1. Set the following inclusion criteria

1. Include patients following pathological confirmation of prostate adenocarcinoma through prostate system puncture.
2. Include patients with PSA < 10 ng/mL, Gleason score < 7, and cT1N0M0 or T2aN0M0 stage (classified as low risk according to D'Amico risk stratification).
3. Include patients who refuse to undergo radical surgery, radiotherapy, or endocrine therapy.
4. Include patients who refuse to accept AS or watchful waiting.

2. Exclusion criteria

1. Exclude patients with a previous diagnosis of prostate cancer with prior radical surgery, radiotherapy, or endocrine therapy.
2. Exclude patients with a history of mental illness, such as depression or severe anxiety, suspected or diagnosed alcohol or drug addiction.
3. Exclude patients if they have diseases that can lead to systemic immune dysfunction.
4. Exclude patients participating in other clinical trials.
5. Exclude patients with surgical contraindications.

3. Instruments for operation

1. Ensure the availability of a cryotherapy system and real-time image fusion ultrasound.
2. Prepare a USB flash drive containing ¹⁸F-PSMA PET/MR imaging data.
3. Choose the appropriate target framework for the puncture. Select different puncture targets based on prostate volume and tumor location. To ensure the precision of cryotherapy, perform 3D customization of puncture targets for some patients.
4. Prepare a V-shaped variable probe (freezing adjustment range of the probe from 1.5 cm to 5 cm in diameter) and two temperature probes.

4. Preparation for operation

1. Connect the USB flash drive to the integrated ultrasound system.
2. Preoperatively Import the patients' imaging data into ultrasound fusion software for 18F-PSMA PET/MR image target planning and marking (Figure 1).
3. Complete the preoperative planning for cryoablation (Figure 2).

5. Procedure

1. Position the patient in the lithotomy position and infuse Levofloxacin (0.5 g) 30 min before the start of surgery. After the import of Levofloxacin, retain a three-lumen pure silicone catheter.
2. Apply ultrasound and preoperative planning markers in ¹⁸F-PSMA PET/MR imaging for intraoperative registration (Figure 3).
3. Complete the targeted puncture of the cryoprobe (Figure 4).
4. Insert the variable probe into the target lesion based on the image fusion results.
5. Place two temperature probes in the perineal puncture, one located anterior to the rectum on the same side or in the Denonvilliers fascia and the other placed proximally adjacent to the neurovascular bundle on the same side.
6. Use a 50 °C constant-temperature saline solution to irrigate the bladder through the three-lumen urinary catheter to protect the urethra and prevent urethral frostbite.
7. Start the cryotherapy system (Figure 5).
   1. Rapidly lower the probe's front end to below -140 °C.
   2. Use ultrasound for real-time monitoring of the ice ball's edge, ensuring it exceeds the preoperative planned tumor coverage area by 0.5 cm while the temperature probe in the rectal anterior space remains above 0 °C.
8. Gradually reduce the freezing power while maintaining the ice ball range for 5 min.
9. Apply helium gas for rapid warming to reach above 15 °C and maintain for 5 min.
10. Repeat the low temperature and rewarming melting cycle.
11. Remove all probes, apply pressure to the puncture site to stop bleeding, and secure with a dressing.
12. Observe the color of the urinary catheter's contents. If the urine is clear, bladder irrigation is unnecessary; if blood is visible in the urine, perform bladder irrigation and transfer the patient to the anesthesia recovery room.
13. Discharge the patient from the hospital 2-3 days after the removal of the urinary catheter post surgery.

6. Evaluation

1. Oncology evaluation
   1. Recheck PSA at 1 and 3 months post surgery, then recheck once every 3 months.
   2. Imaging examination: Recheck ¹⁸F-PSMA PET/MRI at 6 months post surgery; T2WI indicates the disappearance of radioactive concentration in the original right peripheral zone.
2. Functional evaluation (followed by re-examination every month):
   1. Measure the International Prostate Symptom Score (IPSS), which is currently internationally recognized as the best means to judge the severity of lower urinary tract symptoms (LUTS).
   2. Measure the Quality-of-life score (Qol score) to understand patients' subjective feelings about the current level of LUTS.
   3. Measure the maximum urinary flow rate (Qmax) to understand patients' concise objective indicators of current LUTS levels.
   4. Use the International Consultation on Incontinence Questionnaire-Short Form (ICI-Q-SF) to evaluate whether there is urethral sphincter injury after cryoablation.
   5. Measure the International Index of erectile function-5 (IIEF-5) to evaluate whether there is neurovascular bundle damage after cryoablation.

Results

Nine patients underwent surgery successfully, with no intraoperative complications. All 12 lesions were subjected to cryoablation, with a median ablation time of 46 min (ranging from 34 to 65 min). The urinary catheters were successfully removed in all cases 2-3 days postoperatively. The median follow-up time was 37 months (ranging from 14 to 61 months), and the postoperative PSA levels significantly decreased compared to preoperative levels. As of now, the follow-up evaluations for the six patients have shown no oncolog...

Discussion

Radical prostatectomy and radiotherapy remain the primary treatment modalities for localized prostate cancer². However, the relatively high incidence of postoperative complications-such as urinary incontinence and erectile dysfunction after surgery, as well as radiation cystitis and radiation proctitis associated with radiotherapy-leads some patients to refuse these treatments. This refusal is often driven by their fear of postoperative complications and higher demands for quality of life. To avoi...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Endocare Cryotherapy System	CryoCare Touch
fusion ultrasound	BK
Levofloxacin	Beijing Jiluohua Pharmaceutical Co., Ltd
temperature probe	CryoCare Touch
Variable probe	CryoCare Touch