Transurethral microwave thermotherapy

During the last decade, numerous studies have been published presenting the clinical results from the application of TUMT. These studies have used different devices with different treatment protocols and have had different follow-up periods.

Recently, a systematic review of all available randomized comparative trials (RCTs) on TUMT attempted to quantify the therapeutic efficacy . TUMT was somewhat less effective than TURP in reducing LUTS. The weighted mean difference (WMD) for the symptom score at the 12-month follow-up was −1.83, favoring TURP. TURP achieved a greater improvement in Qmax than TUMT (WMD of 5.37 mL/s in favor of resection) . Data on TUMT efficacy from this study are presented in Table 1 . Gravas and colleagues performed a pooled analysis of three studies (two RCTs and one open-label study) of ProstaLund Feedback TUMT with 12-month follow-up. The responder rate was 85.3% and 85.9% in the ProstaLund Feedback Treatment (PLFT) and TURP groups, respectively.

High-quality data regarding morbidity come from the pooled analysis of published randomized studies comparing TUMT with TURP . For patients treated with TURP, the mean length of hospitalization and catheterization time was 4.0 days and 3.6 days, respectively, while in the TUMT group, the corresponding mean values were 0 days and 13.7 days, respectively. More patients treated with TUMT developed dysuria/urgency and urinary retention compared with the TURP subjects. The incidence of hematuria, clot retention, transfusions, TUR syndrome, is reported to be significantly less for TUMT than for TURP. The impact of TUMT on sexual function in terms of erectile dysfunction and retrograde ejaculation also has been studied in comparison with pooled data to be in favor of TUMT .

Retreatment of TUMT is related to treatment failure, whereas retreatment of TURP is related to complications of resection. Reported retreatment rates after TUMT range from 19.8% to 29.3%, but with different mean follow-up durations (from 30 to 60 months) . Hoffman and colleagues found that TUMT patients (7.54 events/100 person–years) were more likely than TURP patients (1.05 events/100 person–years) to require additional treatment for benign prostatic hyperplasia (BPH) symptoms, while in contrast, the retreatment rate for strictures (meatal, urethral, or bladder neck) was found to be 5.85/100 person–years and 0.63/100 person–years for the TURP and TUMT groups, respectively .

It is very difficult to identify predictive baseline parameters for TUMT, because different devices have been used, and studies suggest that a predictive factor for a particular device cannot be applied to the other devices necessarily . Advanced age of the patient, small prostate volume, mild-to-moderate bladder outlet obstruction, and low amount of energy delivered during treatment, however, are considered to be independent baseline parameters predicting unfavorable outcome .

The reported low morbidity and the absence of any anesthesia (spinal or general) needs make TUMT a true outpatient procedure representing an excellent option for patients in high operative risk (American Society of Anesthiologists classifications 3 and 4) who are unsuitable for an invasive treatment . Recommendations from the most popular BPH guidelines on the use of TUMT are given in Table 2 .

Transurethral needle ablation

A significant number of clinical studies on TUNA have been published with different number of patients in each study and different follow-up period. A recent meta-analysis provides high level of evidence on the efficacy and safety of TUNA . Results on Qmax and International Prostate Symptom Score (IPSS) are listed in Table 1 . Comparisons with TURP showed that in the short term, TUNA achieves a similar level of efficacy, but at 12 months the degree of improvement in both subjective and objective variables was significantly lower than of TURP . An older meta-analysis reached to similar conclusions .

TUNA can be performed as an outpatient procedure under local anesthesia and sedation in most patients. The excellent adverse effect and safety profile of TUNA has been documented in several short- and long-term studies. Analysis of pooled data showed that TUNA resulted in a significantly lower number of complications than TURP . The estimated odds ratio of experiencing an adverse event (AE) following TUNA is 0.14 (95% CI 0.05 to 0.41) compared with TURP. This indicates that TUNA has an absolute risk reduction of complications of 19.4% .

The only post-treatment complications having a higher incidence in patients undergoing TUNA include transient urinary retention (from 13.3% to 41.6%) and dysuria . All the other AEs, including mild hematuria, urinary infections, strictures, and sexual dysfunction (erectile dysfunction and ejaculation disorders), are more common in patients undergoing TURP than in those undergoing TUNA.

The combined results of the available studies demonstrated that TUNA had a retreatment rate significantly higher than that of TURP, given that 10% (21/206) of patients undergoing TUNA versus only 1% (3/282) of patients undergoing TURP required new treatments .

Few selection criteria have been identified. TUNA is not suitable for patients who have prostate volumes exceeding 75 mL or isolated bladder neck obstruction . Other studies, however, found that prostate size and shape were not related to treatment response . TUNA is not recommended in patients who have metallic pelvic prosthesis and pacemaker .

Available data suggest that TUNA is an effective and safe MIT for men with even severe symptoms who do not wish to undergo long-term medical therapy, or who are poor candidates for surgery or who are concerned about the adverse effects of TURP .

Transurethral needle ablation

A significant number of clinical studies on TUNA have been published with different number of patients in each study and different follow-up period. A recent meta-analysis provides high level of evidence on the efficacy and safety of TUNA . Results on Qmax and International Prostate Symptom Score (IPSS) are listed in Table 1 . Comparisons with TURP showed that in the short term, TUNA achieves a similar level of efficacy, but at 12 months the degree of improvement in both subjective and objective variables was significantly lower than of TURP . An older meta-analysis reached to similar conclusions .

TUNA can be performed as an outpatient procedure under local anesthesia and sedation in most patients. The excellent adverse effect and safety profile of TUNA has been documented in several short- and long-term studies. Analysis of pooled data showed that TUNA resulted in a significantly lower number of complications than TURP . The estimated odds ratio of experiencing an adverse event (AE) following TUNA is 0.14 (95% CI 0.05 to 0.41) compared with TURP. This indicates that TUNA has an absolute risk reduction of complications of 19.4% .

The only post-treatment complications having a higher incidence in patients undergoing TUNA include transient urinary retention (from 13.3% to 41.6%) and dysuria . All the other AEs, including mild hematuria, urinary infections, strictures, and sexual dysfunction (erectile dysfunction and ejaculation disorders), are more common in patients undergoing TURP than in those undergoing TUNA.

The combined results of the available studies demonstrated that TUNA had a retreatment rate significantly higher than that of TURP, given that 10% (21/206) of patients undergoing TUNA versus only 1% (3/282) of patients undergoing TURP required new treatments .

Few selection criteria have been identified. TUNA is not suitable for patients who have prostate volumes exceeding 75 mL or isolated bladder neck obstruction . Other studies, however, found that prostate size and shape were not related to treatment response . TUNA is not recommended in patients who have metallic pelvic prosthesis and pacemaker .

Available data suggest that TUNA is an effective and safe MIT for men with even severe symptoms who do not wish to undergo long-term medical therapy, or who are poor candidates for surgery or who are concerned about the adverse effects of TURP .

Water-induced thermotherapy

WIT is another thermal-based therapy for BPO that aims to produce heat-induced coagulative necrosis using heated water as a source. The treatment is performed as a 45-minute outpatient procedure without requiring systemic analgesia, because topical lidocaine jelly provides sufficient analgesia .

Limited data on WIT efficacy and morbidity are available . Evidence comes mainly from a single international, uncontrolled, multicenter trial demonstrating symptom reduction and safety (see Table 1 ) . Overall, short-term results seem to be inferior to TURP. No significant ablation is achieved, because the procedure has been associated with a median post-treatment prostate shrinkage of 3.2 cc at 12 months compared with baseline .

Published studies have not reported significant morbidity . Main AEs included prolonged or excessive dysuria (11.2%), prolonged and excessive hematuria (22.4%), bacteriuria or urinary tract infection (32.8%), and urinary retention subsequent to the post-treatment catheterization period (12.0%). No patient suffered from newly occurring permanent erectile dysfunction or retrograde ejaculation, while interest in sex and sexual activity were not affected or were slightly improved by WIT .

Data regarding durability are lacking. On an intention-to-treat basis, the retreatment rates were higher: 10.4% after 12 months, 23.2% after 24 months, and 36% after 36 months . No predicting parameters have been identified using logistic regression models to evaluate baseline parameters for successful outcome . Protrusion of a median prostate lobe is a relative contraindication for this therapy .

It is obvious that randomized studies against one of the standard treatments are required, thus WIT is not recommended by clinical guidelines and is considered to remain investigational (see Table 2 ).

Transrectal high-intensity focused ultrasound

Randomized controlled studies comparing HIFU to the standard therapy have not been published. A non-RCT comparing TURP with four MITs including transurethral electrovaporization (TUVP), visual laser ablation of the prostate (VLAP), TUNA, and HIFU has performed . The clinical results of HIFU are presented in Table 1 . Increase in Qmax after HIFU was smaller than the improvement achieved after TURP. Data analysis from a study with the longer follow-up showed that 43.8% (35/80) of the patients required TURP within 4 years . In the group of responders, IPSS improved from 19.6 to 8.5 after 12 months and remained practically unchanged during the 4-year follow-up, while Qmax increased from 9.1 mL/s to 11.8 mL/s at 12 months and subsequently deteriorated to 10.2mL/s at 4 years.

In general, the treatment is tolerated well but requires general or regional anesthesia. The most prominent AE is prolonged urinary retention, thus a suprapubic catheter is offered to the patients postoperatively . Complication rates are low because of absence of any urethral manipulation. Effects on erectile and antegrade ejaculation are uncommon. Hematospermia can be noticed up to 4 to 6 weeks in up to 80% of sexually active men .

Predictors of unfavorable outcome include large prostates (greater than 75 mL), presence of a pronounced middle lobe, presence of prostatic calculi (caused by attenuation of ultrasound), and higher grades of bladder outlet obstruction .

To date, the interest for treating BPH patients with HIFU has declined while there is a shift toward the use of HIFU for the treatment of prostate cancer. Because of the lack of high-quality data, HIFU is considered as an investigational treatment modality by most of the guidelines (see Table 2 ).

Holmium laser enucleation of the prostate

Several clinical studies have shown the efficacy and safety of holium laser enucleation of the prostate (HoLEP) . A recent meta-analysis of the available RCTs comparing HoLEP with TURP showed that there was no statistically significant difference between HoLEP and TURP in terms of Qmax (WMD was 0.59) at 12 months after treatment . Unfortunately, this meta-analysis does not provide the pooled values of Qmax and IPSS at baseline and during follow-up; therefore it has not included in Table 1 . Thus the results from the largest RCT comparing HoLEP with TURP are presented there . On the other hand, this meta-analysis offers significant information regarding perioperative variables and AEs . No statistically significant differences between pooled estimates were noted between HoLEP and TURP for urethral stricture (2.6 versus 4.4%), blood transfusion (0 versus 2.2%), and reintervention (4.3 versus 8.8%). The overall complication rate, however, was 19 of 232 (8.1%) in the HoLEP group and 37 of 228 (16.2%) in the TURP group, with a statistically significant difference in the pooled estimates. Pooled data suggest that HoLEP is superior to TURP in terms of catheterization time, hospital stay, and blood loss. In contrast, pooled estimates showed a benefit of TURP over HoLEP for duration of operation . Montorsi and colleagues reported that there was no TUR syndrome in the HoLEP group, versus 2.2% of patients in the TURP group.

The impact on erectile dysfunction and retrograde ejaculation is very similar between the two groups. The erectile function did not show a decrease from baseline in either group. In addition, Kuntz and colleagues reported that 74% of sexually active patients in the HoLEP group and 70.3% in the TURP group had retrograde ejaculation.

Gilling and colleagues performed a meta-analysis of four RCTs comparing HoLEP and TURP. They found that urodynamic relief of obstruction (PdetQmax and Schaffer grade) was superior with HoLEP compared with TURP, but only when prostate volumes were greater than 50 g. Studies evaluating durability of HoLEP are now available. Recently, Gilling and colleagues reported the results from a series of patients with a mean follow-up of 6.1 years. HoLEP achieved durable results in terms of Qmax, quality of life (QOL), and IPSS, while the reoperation rate was 1.4%. Similarly, Elzayat and Elhilali found that the objective and subjective improvements after HoLEP remained sustained at 6 years, with a reoperation rate of 4.2% for recurrent BPH obstruction.

HoLEP has no size limitation and has been shown to be effective for large prostates that traditionally have been treated by open prostatectomy . The main evident advantages are reduced blood loss and shorter catheterization and hospitalization time. Recent, long-term (5 years) data from a RCT comparing HoLEP with OP demonstrated similar durable subjective and objective improvement for both groups and a reoperation rate of 5% in the HoLEP group and 6.7% in the OP group .

HoLEP is recommended by the guidelines (see Table 2 ); however, the main criticism of HoLEP includes a significant learning curve (requiring 30 to 50 cases), purchase cost, and the difficulty in tissue removal.

Photoselective vaporization of the prostate

PVP using the high-power (80 W) potassium-titanyl-phosphate (KTP) laser represents the latest evolutionary development in laser and is attracting the interest of urologists.

Initial studies on the 80 W setting have shown promising outcomes . Mean increase in Qmax ranged from 106% to 253%, and mean IPSS improvement varied from 59% to 84%. Reduction in prostate volume ranged from 37% to 53% . There is only one randomized study; however, that compares PVP with TURP, and results are displayed in Table 1 .

Catheterization time is generally less than 24 hours, while in one study, 44 patients (32%) were left without a catheter at the end of the procedure . The perioperative morbidity is low, with the most frequent complications being the need for recatheterization (range from 1% to 15.4%), dysuria (from 6.2% to 30%), and minor hematuria (up to 18%). One of the main advantages of PVP is the virtually bloodless tissue ablation, resulting in absence of significant bleeding and need for blood transfusion. No TUR syndrome rate was reported in any study. Between 36% and 55% of sexually active men experienced retrograde ejaculation after treatment . In the only RCT, PVP was superior to TURP in terms of blood loss, catheter time, and duration of hospital stay .

Long-term results of this technique are still missing. A study with the longest follow-up (5 years) showed that a significant improvement in American Urological Association (AUA) symptom index and Qmax after PVP that remained durable during follow-up . This study, however, suffered from a very high attrition rate (68% and 85% at 3 and 5 years, respectively).

Published studies also demonstrated that the 80 W KTP laser seems to be a safe and effective means for treating men who have large prostates (mean volume greater than 100 mL) . The mean lasing time ranged from 79 to 123 minutes. Qmax, IPSS, and QOL scores showed significant improvements without the presence of TUR syndrome or the need for blood transfusions. The new 120 W high-performance system (HPS) recently was introduced, aiming at a faster tissue removal in less lasing time and the ability to treat large glands in an acceptable time. A consideration, however, is that the high-power settings may result in higher complication rates including capsule perforation, bladder perforation, or injury of the orifices and decreased haemostatic capability .

KTP laser vaporization has a relatively short learning curve, but caution is required when the prostate gland or the median lobe is very large. Another consideration is that the recently introduced 120 W HPS with the high-power settings may require a longer leaning curve.

The lack of randomized studies and long-term data does not allow definitive recommendations about the position of PVP for managing LUTS (see Table 2 ).