Main local treatments for localized prostate cancer: literature review

2021-11-12 10:47:36 By : Mr. David Zhou

© 2021 MJH Life Sciences and Cancer Network. all rights reserved.

© 2021 MJH Life Sciences™ and Cancer Network. all rights reserved.

For highly selected patients, local treatment of prostate cancer can balance the undertreatment and overtreatment of local prostate cancer. There are no long-term oncology results in any way. Patients should be informed about the results currently available, the need to follow a strict follow-up protocol, and the need for additional targeted therapy or future radical treatment in the case of recurrence.

Prostate cancer (PCa) is the most common non-skin cancer among American men. By 2020, approximately 191,930 men will be diagnosed and 33,330 men will die of PCa. 1 With the introduction of extensive prostate-specific antigen (PSA) screening, most men are diagnosed at the localized PCa stage. There are several mature treatment options, such as radical prostatectomy, radiotherapy, and full gland cryotherapy, which can be used for localized PCa. Although these treatments are very effective in providing a cure at the local stage, they are often associated with debilitating adverse reactions (AE), such as erectile dysfunction and urinary incontinence. Therefore, patients usually completely delay or postpone the treatment of PCa.

Over the past decade, active surveillance (AS) for low-risk and very low-risk PCa has increased, which reduces the sequelae of overtreatment and radical treatment. However, as pointed out in the PROTECT trial, approximately 50% of AS patients will eventually require treatment due to disease progression. 2 In addition, some patients will progress to a non-local disease stage during the monitoring period, thereby missing the chance to cure the cancer. Better selection and monitoring of risk stratification methods for AS patients is an area of ​​active research. However, for many patients, the increased tumor risk associated with AS and the quality of life issues associated with whole gland therapy are unacceptable, which is understandable. Therefore, the ever-evolving literature surrounding focused treatment has attracted widespread attention from patients and providers.

Local treatments treat diseased areas of organs while preserving normal surrounding tissues to maintain organ function and minimize AEs. The local treatment of malignant tumors has been successfully applied to breast cancer, thyroid cancer, lung cancer, colon cancer and kidney cancer, and its oncology results are comparable to those of radical surgical resection. Recently, local treatment has been applied to PCa. Although PCa is primarily a multifocal disease, a single focus of cancer (often referred to as an indicator focus) is thought to promote progression and hide the genetic precursor cells of advanced cancer. 3 Pre-treatment disease location used to be a challenge for PCa, but with the advancement of multi-parameter MRI (mpMRI) for diagnosis and staging, significant progress has been made in this field. mpMRI is highly sensitive to high-grade PCa and detection index lesions, which are 72% and 80% respectively when examining the overall pathology. 4 With the aid of the ultrasound fusion platform, the disease area can be accurately located and targeted. Transrectal or transperineal approach. Several devices that provide ablation energy have been used to treat specific disease areas. Standard treatment programs such as surgery and radiotherapy are also being revised and subsequently studied to evaluate the safety and effectiveness of some prostate treatments.

This article describes the available topical treatment options for the main treatment of topical PCa, as well as their respective results, shortcomings, and applicability.

We reviewed PubMed using multiple permutations of relevant search terms, including but not limited to prostate cancer, focal therapy, focal ablation, focal high-intensity focused ultrasound (HIFU) cryoablation, focal laser ablation, irreversible electroporation, photodynamics Therapies, brachytherapy, radiofrequency ablation, partial prostatectomy, and focal transurethral ultrasound ablation (TULSA). We focus on studies describing the main treatments for PCa. Studies on salvage focal therapies are excluded. All options The selected article was reviewed in full.

In 2012, in response to growing concerns about the harm caused by overtreatment of PCa, the US Preventive Services Task Force (USPSTF) discouraged the use of PSA screening to detect PCa. The USPSTF has since changed its stance on PSA screening due to longer follow-up of patients in clinical trials, showing that the number of screenings required to prevent 1 PCa death has decreased, and due to more frequent use of AS to avoid Overtreatment of indolent diseases. The USPSTF now makes C-level recommendations for PSA screening based on a joint decision between doctors and patients. Although the increasing use of AS for the treatment of low-risk diseases has reduced overtreatment and related AEs, it is still challenging for any patient and their doctor to decide to stop AS and seek ultimate full-glandular treatment. The termination of AS occurred due to the progression to an aggressive disease and the anxiety of patients and doctors about untreated cancer. There are clearly unmet needs that require a finer balance of treatment options between AS and radical treatment to best treat visible cancer while minimizing AEs.

13% to 38% of radical prostatectomy specimens contain a single cancer foci. 5 Histopathology of index lesions predicts the natural course of PCa in most patients. 6 Advances in MRI technology, including improved solutions and the introduction of 3 Tesla machines, can better locate PCa lesions. The overall pathology of the prostatectomy specimens showed that the lesions were consistent with the lesions visible on MRI. 4 In addition, the combination of systematic biopsy and MRI targeted biopsy can optimally sample the prostate to determine the range and multifocality of PCa. Image-guided positioning enables researchers to target and treat these lesions through a variety of ablation energies, radiation, and partial gland surgery. These treatments can preserve the anatomy that maintains abstinence and erectile function, thereby minimizing AEs.

There are several local treatment modalities that can be used to selectively treat diseased areas in the prostate. They differ in their energy sources and their effects on prostate tissue. The choice of local treatment for PCa depends on the availability of local treatment in the treatment center, the training of doctors, the size of the prostate, the location of the indicated lesion, the scope of the disease outside the indicated lesion, the prostate and patient-specific factors. The figure summarizes the widely used patient selection criteria and common disease treatments.

Here, we summarize the available treatments, suggested mechanisms, and the results of key studies. The important oncology results of these studies are noted in the table.

HIFU uses high-energy ultrasound to target and ablate the parabolic region of prostate tissue. The prostate was imaged with a transrectal ultrasound probe and the PCa lesions were mapped out. Ultrasonic energy then induces cell necrosis through thermal energy, heating the tissue to 100°C. 7

Several devices are already on the market and have been researched, including Abatherm, Focal One and Sonablate 500. HIFU has been studied in the main whole gland treatment, rescue treatment and main focus treatment settings. National Comprehensive Cancer Network (NCCN) guidelines recommend HIFU rescue for PCa that has relapsed from radiotherapy. However, there are no guidelines for the use of HIFU in major environments. The FDA approved HIFU for tissue ablation in 2015, but due to insufficient data on its efficacy in the primary setting, it was not approved for PCa treatment.

A multicenter study reported 5-year results in 625 men who received primary focal HIFU. The study included patients with topical Gleason 9 or lower, cT3b or lower, and PSA ≤30 ng/mL. The main outcome is failure-free survival (FFS), which is a composite outcome that avoids whole gland therapy, systemic therapy, metastasis, and PCa-specific death. In this study, 83% of the cohort had Gleason grade 6 or 7 disease, and 75% had a PSA <10 ng/mL. The 5-year FFS for all patients was 88%. In the pre-specified subgroup analysis, the FFS of low-risk, intermediate-risk, and high-risk patients were 96%, 88%, and 84%, respectively, and the metastasis-free survival rates were 96%, 99%, and 97%, respectively. The most common complication is urinary tract infection, with an incidence of 10.4%. The most serious complication was the formation of a rectal-urethral fistula in 2 patients (0.3%), of which 1 required reconstruction. During 2 to 3 years of follow-up, 80% of patients reported no urine leakage at all, and 98% of patients did not use a changing pad. There are no reports of erectile function and retreatment rates. 8

Recently, Abreu and colleagues evaluated the use of hemigland HIFU in the primary setting of 100 men with localized PCa. According to the NCCN risk stratification, 20% is low risk, 50% is moderately favorable, 17% is moderately unfavorable, and 5% is high-risk. The 2-year survival rates of no treatment failure, local recurrence of Gleason 7 or higher, repeated local HIFU, and radical treatment were 73%, 76%, 90%, and 91%, respectively. Among men undergoing post-treatment biopsy, 17% of patients had field recurrence, and 14% of patients had field recurrence of Gleason grade group 2 and higher. As measured by the International Index of Erectile Function (IIEF), no decrease in efficacy was found after treatment. The abstinence after treatment is also excellent. 9 In another study by Nahar and colleagues, 52 patients received primary focal HIFU treatment, and 67% of them had a Gleason score of 7 or higher. Noted on-site (17%) and off-site recurrence (13%). Approximately 10% of patients have grade 3 or higher complications. In all patients with available data, urinary and sexual functions returned to baseline levels at 3 to 6 months and 12 months, respectively. 10

According to existing short- and medium-term studies, HIFU is characterized by good curative effect, low on- and off-site recurrence rates, and retention of urinary and sexual function. However, local HIFU has several limitations. The patient must have no restrictive rectal pathology, which prevents the use of transrectal probes for delivery. Large glands >40 g may be a contraindication for HIFU with some old equipment, because the focal length may be insufficient. 11 Compared with posterior lesions, anterior lesions treated with primary HIFU require additional treatment because the depth of penetration ultrasound energy is limited. 12 Extensive calcifications may also be a limitation; they can cause acoustic shadows, preventing the passage of therapeutic sound waves. Further efforts are being made to identify patients who will fail local HIFU treatment, so they may be offered a different local mode or full gland treatment.

Cryoablation is rapid cooling by placing the transperineal needle to a temperature of –40 °C. It leads to the formation of ice balls and subsequent tumor lysis. Pre-clinical trials have shown that a margin of at least 1 cm around the target tissue is required to ensure cancer ablation. 13

Most of the data for focal prostate cryoablation studies come from the COLD (Cryogenic Online Data) registry. The largest prospective registry of local cryoablation reported the early results of 122 men; in most cases, they had a moderate risk disease, confirmed by mpMRI targeted biopsy or perineal mapping, and the maximum cancer core length was 6 mm. These patients were definitely selected because they were not suitable for HIFU (because of anterior disease, anteroposterior height greater than 3 cm, or extensive calcification). The standard FFS is the main result, with an incidence rate of 90.5% at 3 years. According to risk stratification, FFS is better in intermediate-risk diseases (93%) compared with high-risk diseases (84%). At the last follow-up, a total of 6.5% of patients required additional local cryotherapy. In a two-group subgroup analysis stratified by PSA, the FFS of patients with PSA <10 ng/mL (97%) was higher than that of patients with PSA >10 ng/mL (84%). 14

27.8% of men reported complications; urinary tract infections and temporary urinary retention were the most common. Serious complications included osteomyelitis in a conservatively treated patient, and no rectal urethral fistula was reported. At 3 years, 87% and 89% returned to the baseline International Prostate Symptom Score (IPSS) and IIEF score, respectively. 15

Another prospective single-institution registration study reported that 119 men who received primary local cryotherapy had slightly lower FFS, which was 73% and 56% at 3 and 5 years, respectively. The survival rate without radical treatment was also reported, with the 3-year and 5-year survival rates being 83% and 70%, respectively. 16 Similar results for hemispheric ablation have been noted. In a retrospective study of 160 predominantly moderate-risk cancer patients, FFS without retreatment was 85% at 5 years. A high baseline PSA heralds failure. 17

Cryotherapy is not the preferred energy method for the treatment of posterior or apical tumors, because surrounding tissue damage may occur, affecting the neurovascular bundles, and then affecting erectile function. 18 Therefore, the choice of patients is critical to the success of local cryotherapy. Similarly, cryotherapy may not be suitable for small glands, because the swollen ice ball may extend beyond the prostate. 18 However, although these preferences for tumor location and prostate size have been repeatedly seen in the literature, trials with clear selection criteria do not support or refute these preferences.

Photodynamic therapy (PDT) uses oral or intravenous drugs. These drugs are inactive before photosensitization. At this time, they form reactive oxygen species and cause tissue destruction. The laser fiber is aimed at the prostate, usually guided by transrectal ultrasound. Several types of photosensitive drugs are used, which are generally classified as tissue-based or vascular-based according to the location where the drug is activated. It may take several days for these drugs to reach their maximum dose in the tissues, while vascular-based drugs activate within a few minutes after photosensitization. 19

In a large phase 3 randomized controlled trial, patients with low-risk PCa were randomly assigned to AS or Padreporfin vascular-targeted PDT. The median follow-up time was 24 months, and 206 men were randomized to receive PDT. The main outcome is time to progression, composite outcome with 4 or more positive cores, any Gleason pattern 4 or higher, at least 1 cancer core longer than 5 mm, PSA> 10 ng/mL for 3 consecutive measurements, any T3 PCa, or transfer. The study measured the median time for PCa to progress from low-risk to medium-risk or high-risk; this time in the PDT group was longer than that in the AS group, at 28.3 months and 14.1 months, respectively (P <.0001). Compared with the AS group, more men in the PDT group had a negative biopsy at 24 months (49% vs. 14%; P <.0001), while fewer men in the PDT group received radical radiation or surgery (6% Right 29%; P <.0001). At 24 months, erectile and urinary functions were similar in the two groups. The AEs in the PDT group were pain, urethral stricture, urge incontinence and urinary retention. 20

Other studies on relatively small cohorts have shown similar short-term results. In a prospective trial, 82 men with low-risk PCa received PDT. The primary endpoint is progression-free survival (PFS), which is defined as intermediate-risk or high-risk group according to D'Amico classification or radical treatment. The median PFS was 86 months, and only 24% of patients received radical treatment. twenty one

Overall, compared with AS, PDT can effectively delay the progression of low-risk cancers. Potential disadvantages of PDT include the need to avoid direct sunlight for 48 hours after surgery to reduce AEs and the possibility of allergic reactions to photosensitizers.

Irreversible electroporation (IRE) uses microsecond electrical pulses to create holes in the cell membrane. Although reversible electroporation allows temporary changes to cells, IRE can cause cell destruction because the cells cannot maintain homeostasis. Compared with other ablation methods, IRE seems to protect peripheral nerves and blood vessels from collateral damage. 22 In theory, this characteristic suggests that IRE is more suitable for the local treatment of PCa than other ablation methods. During the IRE of prostate tumor, the patient was placed in the lithotomy position under general anesthesia, and the muscles were paralyzed to reduce muscle spasms. The needle probe is placed through the perineum, usually using a brachytherapy template. twenty three

Valerio and colleagues studied the safety and feasibility of focal IRE. A total of 34 patients (mainly low-risk and intermediate-risk PCa) received focal IRE. No grade 3 complications were found. During the 6-month follow-up, from a functional point of view, 100% of men were capable after focal IRE, and 95% were effective. According to mpMRI assessment, approximately 20% of patients have residual cancer. 24 In the Phase 1/2 study, van den Bos and colleagues evaluated the histopathology of prostate tissue in men who received IRE, and all cells in the electrode area were completely ablated. No jumping lesions were found, proving the effectiveness of IRE as a method of ablation. 25

Blazevski and colleagues evaluated their IRE experience in 123 men with PCa, most of whom (91%) had intermediate-risk disease, with a median follow-up of 3 years. FFS is defined as whole gland treatment, systemic disease or death, which is 96% at 3 years. In up to 9% of patients, on-site recurrence is noted. Eighteen men needed retreatment: 12 received repeated IRE and 6 received full gland treatment. The functional results were very good, 98% of men remained cushionless, and 76% had no changes in erectile function. 26

There are no randomized trials comparing IRE with radical prostatectomy in the literature. However, Scheltema and colleagues performed a paired comparison, comparing 50 patients with cT1c-T2b with monofocal disease with 50 men who underwent robot-assisted nerve-sparing radical prostatectomy. There were no significant differences in baseline oncology and functional characteristics. At 12 months, men who received IRE had better urinary control and sexual function than men who received robot-assisted laparoscopic radical prostatectomy (RARP), but men who received IRE had a higher rate of local failure (29.5%). 27

IRE is a promising local treatment method. However, a larger study using the appropriate control arm is needed to determine its role in the treatment of PCa, as well as to determine potential selection criteria and shortcomings.

Whole gland brachytherapy and salvage brachytherapy have been used to treat local PCa and have been recommended by NCCN guidelines for the treatment of low-risk diseases. However, there is little evidence on the use of primary MRI-guided brachytherapy for the focal treatment of PCa. Although the field has anticipated the promise of focal high-dose rate (HDR) brachytherapy for PCa, in many cases, clinical trials have not brought promising results. 28

King and colleagues reviewed their experience with focal MRI-guided brachytherapy in a large cohort of 354 men: 40%, 39%, and 21% of patients had very low-risk, low-risk, and medium-risk, respectively. Risk disease. During a median follow-up of 11 years, 22 men (6.2%) developed metastatic disease. The 12-year metastasis rates of patients with very low-risk, low-risk, and medium-risk diseases were 0.8%, 8.7%, and 15.7%, respectively.

More importantly, the 12-year PCa-specific mortality estimates are 1.6%, 1.4%, and 8.2% for extremely low-risk, low-risk, and medium-risk diseases, respectively. Due to the high rate of metastasis and PCa-specific mortality, the authors concluded that some gland ablation and brachytherapy may not be suitable for patients with intermediate-risk diseases. 29

Other prospective studies with short-term follow-up showed consistent results. In a 4-year follow-up study, the biochemical relapse-free survival rate after focal HDR brachytherapy was very poor, with a survival rate of 70% for 30 patients. 30 There are no other relevant oncology results, such as FFS or salvage all-glandular therapy reported in this study.

Focus laser ablation (FLA) is an MRI-guided technique that uses low-power laser fibers to transfer thermal energy through the rectum to soft tissue targets. The tissue ablation temperature exceeds 60°C. This technique is suitable for intracranial tumors. 31

Only a few small studies have reported results for the primary treatment of PCa. A phase 2 trial of 27 men, mainly suffering from low-risk diseases, receiving FLA treatment up to 2 MRI visible lesions. 96% of men used MRI-targeted biopsy 3 months after treatment and found no residual cancer. However, 37% of men detected residual cancer in a follow-up systemic biopsy at 12 months. Complications are good. Hematuria, perineal ecchymosis, and urinary retention are the most common AEs. 32 There was no significant difference between the IPSS or the Male Sexual Health Scale (SHIM) scores at baseline and at 12 months. In another study by Lepor and colleagues, 25 men with a Gleason score <8, cT1c-T2a, and PSA <10 ng/mL received FLA treatment and were monitored by MR thermometry. At 3 months, no decrease in IPSS or SHIM score was found, and 96% of men had a negative ablation zone biopsy. 33

In a larger prospective trial involving 120 patients who received FLA primarily for low- or intermediate-risk disease, 15% of patients had residual clinically significant disease during follow-up MRI-targeted biopsy; 17% needed something Various forms of retreatment. During the research period, technological changes significantly limited this research. 34 In another prospective study of primary FLA that reported two years of oncology results, 18.8% of patients had clinically significant PCa at follow-up biopsy. 35

The contraindications of prostate volume limitation and FLA are not clearly defined in the literature. 36

Local radiofrequency ablation (RFA) has been studied as a treatment for cancer in various organs, including liver and kidney. It provides heat energy by using intermediate frequency alternating current through the perineal probe. 37

There is only one prospective phase 2 study in the literature. It recently reported short-term results in 20 men who received bipolar RFA, 90% of whom had Gleason 7 disease. In a 6-month follow-up targeted biopsy, 80% of men did not have clinically significant PCa in the treated lesion. Using the extended prostate cancer index comprehensive questionnaire, it was found that 89% of patients without baseline urinary dysfunction had no urinary incontinence at 12 months. Using the response to IIEF, the researchers found that 91.7% of patients without baseline erectile dysfunction reported the ability to achieve adequate erections with or without phosphodiesterase 5 inhibitors. 38 No serious AEs have been reported.

Due to the lack of literature on focal RFA in this situation, additional research is needed to establish selection criteria and shortcomings.

Partial prostatectomy is a subtotal resection of the prostate tumor. The cancer control results of this method are rarely seen in the literature. However, recently, the short-term results of a single-arm multicenter prospective trial of robotic partial prostatectomy for anterior tumors were reported. 39 Seventeen patients were recruited, and the main tumors of the anterior urethra were visible on MRI. All patients underwent robotic partial prostatectomy by transperitoneal method. The perioperative results were very good, and no grade 3 complications were reported. The three-month abstinence rate and erectile function rate were 100% and 83%, respectively. No long-term oncology results were reported. However, the 3-year local recurrence-free survival rate was 67%, and 24% of men underwent a complete radical prostatectomy.

Although this is a new method for the treatment of PCa in the anterior zone, only a few men meet the inclusion criteria for preurethral tumors, and the local failure rate is high, and some people will soon need full gland treatment.

MRI-guided TULSA is a novel procedure in which the prostate tissue is ablated in a continuous scan using directional ultrasound. The ablation zone was monitored by MR temperature measurement. It is mainly studied as a whole gland therapy for PCa.

Recently, the TULSA-PRO (designated technology manufacturer Profound Medical) ablation clinical trial protocol was developed, and a single-arm multi-center trial of PCa whole gland therapy was completed. Patients with Gleason 6 and 7, cT1 to cT2b, tumors visible on MRI, and PSA <15 ng/mL were included in the study. Patients with prostate volume> 90 cc, intra-prostatic calcification> 1 mm, and prostate tumors within 3 mm of the apex of the prostate on MRI were excluded. The main goal of the trial is safety and effectiveness, which is defined as a decrease in PSA equal to or greater than 75%. The secondary oncology goal is the improvement of the disease on repeated biopsy, defined as no cancer found on the 10-core biopsy at 12 months or a decrease in cancer grade. IPSS was used to evaluate urinary function, and IIEF score was used to evaluate erectile dysfunction. A total of 115 men received full gland treatment, of which 33% had low-risk diseases and 67% had intermediate-risk diseases. At 12 months, 8% of patients had grade 3 complications, of which urinary tract infection and urethral stricture were the most common. A total of 96% of patients achieved the main goal of a PSA drop of >75%. A total of 23% of patients have moderate erectile dysfunction requiring medical management. Between 75% and 80% of men did not find cancer during the 12-month biopsy. Risk factors for treatment failure include intra-prostatic calcification, failure to achieve >96% thermal dose coverage, and >3 lesions in the prostate imaging report and data system at 12 months. 40

TULSA-PRO is awaiting FDA approval, and further studies are underway to study its role in the local treatment of PCa. The results of a number of treatment-first-resection studies have been reported, demonstrating the safety and potential efficacy of topical TULSA. A phase 1 study investigated the feasibility of MRI-guided TULSA. Six men with 1 to 2 MRI visible lesions away from the neurovascular bundle were selected. No treatment-related complications were reported in the 3 weeks before RARP. In surgical pathology, no residual wild cancer was found. 41

Local PCa treatment reduces the risk of progression and PCa-specific death, but the significant adverse long-term functional outcomes of local PCa treatment with prostatectomy and radiotherapy have been well characterized. As many as 18% of patients report serious distress due to urine leakage, and 43% of patients suffer from sexual dysfunction at 15 years. 42 AS may retain the functions of some carefully selected patients, but at the cost of a higher risk of progression before the final treatment. For many intermediate-risk patients whose risk of AS progression is unacceptably high but the quality of life of whole gland therapy is too low, topical therapy provides a possible solution. The data we discussed well support this potential benefit regarding functional preservation. Compared with the incidence of whole gland treatment, the incidence of incontinence and erectile dysfunction of topical treatment is milder in terms of maximum extent and duration of recovery. Even in the most modern series of nerve-sparing robotic prostatectomy, the report rate of severe incontinence and erectile dysfunction can be detected, which is not seen in any local treatment cohort. 43

However, for each local treatment mode of PCa, many questions remain unanswered. The longest oncology result of HIFU and cryoablation is 5 years. As expected in the interim results, the metastasis-free and cancer-specific survival rates are very high. Most patients avoid radical whole-glandular therapy, and the FFS of men with intermediate-risk disease 5 years after local HIFU is as high as 88%. Time limit, but it is reported to be as low as 70% at 5 years. Many patients receiving cryotherapy and HIFU require repeated local treatments to determine cancer control. 44 Most patients who receive topical treatment avoid radical treatment, and the rate may be lower than that of patients with intermediate-risk disease who initially seek AS in contemporary protocols. 2,45 However, as far as we know, only one randomized trial comparing any focal treatment with AS reported this result, and this was for a low-risk cohort. 28 As for energy methods other than HIFU and cryoablation, it is unclear whether similar interim results will be seen.

Other considerations are the results of patients who need to be rescued after topical treatment, and our understanding is limited to small retrospective series. Marra and colleagues conducted a systematic review of the short-term oncology and functional results after the curative salvage treatment after topical treatment; they found that there were almost no significant differences between the results after the main curative treatment, but the overall quality of the evidence was low. 46 Another recent group of 45 men who underwent HIFU prostatectomy found that one-third of men needed additional radiation therapy or androgen deprivation treatment at 12 months after surgery, and only 65% ​​of patients did not have a pad. Shows that compared with primary prostatectomy, the prognosis is worse. 47

As the literature matures, patient selection criteria for topical treatment continue to evolve. Many of the above studies have evaluated various cancer risk groups. As expected, high-risk patients are not as well as intermediate- or low-risk patients. 48 The ideal tumor location has been widely described, but it is not well learned. A recent retrospective article compared the focal HIFU results of anterior and posterior tumors and found that in a multivariate analysis, the anterior position can predict treatment failure. 12 This has been assumed in the previous literature. The swelling of the prostate during treatment can transfer the target lesion, and this effect is described as having an exaggerated effect on the anterior lesion. 13 No comparable study on tumor localization of cryotherapy has been published. However, posterior tumors are considered unfavorable for this type of treatment, because the destruction of the collateral tissue of the neurovascular bundle is not seen in focal HIFU. 13 The influence of other clinical factors has also been described, such as PSA >10 ng/ml; in multiple studies, this has been proven to be a risk factor for treatment failure. 48

In the age of AS, the Delphi consensus statement claimed that the ideal candidate for local treatment is a small single-focal mpMRI visible lesion, which is confirmed to be intermediate-risk disease by biopsy, and if it is confined to a single hemi, the maximum volume is 3 mL. 48 It is well known that due to the need for intensive follow-up imaging and biopsy, and the possibility of retreatment in most protocols, a high level of long-term patient compliance is required. Current guidelines do not recommend major topical treatments outside the scope of clinical trials.

For highly selected patients, local PCa treatment can balance the undertreatment and overtreatment of local PCa. There are no long-term oncology results in any way. The mid-term oncology results of HIFU and cryoablation seem to be promising, and the functional results are better than any form of whole gland therapy. Patient selection is still the key to the success of local treatment. Patients should be informed about the results currently available, the need to follow a strict follow-up protocol, and the need for additional targeted therapy or future radical treatment in the case of recurrence.

Financial disclosure: The author has no significant economic interest or other relationship with the manufacturer of any product or any service provider mentioned in this article.

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