Patient group
In the German healthcare system, patients are commonly referred to urologic surgeons typically after failed attempts with pharmaceutical treatments and often with late stage urodynamic issues due to years of insufficient treatment of LUTS. While PUL has not been studied in this specific population, these patients were nonetheless often attracted to the less invasive nature of this treatment, when compared to TURP or other ablative procedures. For this reason, we sought data outside of rigid study protocols and was reflective of our daily clinical practices. We offered PUL as an alternative procedure to all patients who were candidates for TURP, without restrictions as to severity of prostatic obstruction. Because PUL was designed for patients with lateral lobe obstruction, we excluded only patients with an obstructive median lobe seen on the initial cystoscopy. Previous trials also had many other exclusion criteria, such as oral pharmacotherapy without washout, history of urinary retention, decompensated urinary bladder, PVR greater than 250 ml, recurrent prostate-related hematuria, and prostate volume greater than 60 ml [
21‐
24]. A limitation of this study may be that those patients who received PUL were not compared against one of the accepted surgical treatments. However, in parallel, the formal BPH-6 study, which did comparisons with TURP, was also enrolling patients [
19] so we were able to compare our results with those of the randomized study.
Comparison with other PUL studies
Of the patients enrolled, 38% suffered from severe obstruction that would have excluded them from prior clinical studies. Despite inclusion of these patients, our results are comparable to those of previously published studies on PUL in rigorously selected subject populations, including the pivotal LIFT study that resulted in US Food and Drug Administration (FDA) approval of the UroLift
® implant system [
21‐
24]. Symptomatic and quality of life improvements were very similar to those reported for LIFT, with 1 year IPSS and QOL improvements of 10.5 vs. 10.8 and 1.93 vs. 2.4, respectively [
22]. When further examining urinary flow and residual volumes, however, a greater difference can be seen. At 1 year, Qmax increased only 2.97 versus 4.0 ml/s in LIFT, but PVR results significantly decreased 63 ml, while no significant difference was seen in LIFT [
22]. These differences might be explained by the fact that our study included men with much lower baseline flow rates and much higher residual volume or even those with an in-dwelling catheter. Very low flow rates may be a function of detrusor functionality, where dis-obstruction may have a less marked effect. The additional analysis in Table
3 substantiates that the subgroup patients who would not have been accepted in a published study, demonstrated a similar outcome. Several studies have shown that PVR change is typically not significant and is poorly reproducible in populations where high PVR is excluded [
25,
26].
Adverse effects were minimal and the rate appeared to be even lower than that in the LIFT clinical study [
22]. Perhaps this could be due to the fact that a third of our patients continued α-blockers therapy for a month following the implant. Also, the LIFT study involved a follow-up at 14 days, where specific questions were asked to elicit adverse event details, while our first follow-up was at 1 month with typical general history questions asked.
Our implantation execution differed from the LIFT experience [
22]. We used general anesthesia in 62 of the 86 patients (72%), a postoperative indwelling catheter for 1.22 days, and 2.17 days of hospitalization. In the LIFT study and other studies conducted in North America, patients under local anesthesia usually were not catheterized and did not require hospitalization. With increasing surgeon experience, our operative times decreased, and 24 of our patients underwent the procedure successfully under local anesthesia. Our different delivery of care was not related to our inclusion of more severely obstructed patients. The difference was largely related to the dynamics of the German health care reimbursement system that is different to the United States.
Our results demonstrated durability of the improvement in voiding up to 24 months as judged by symptom score, PVR, and Qmax, corroborating the previous PUL studies, even in the group of those who would have been excluded in any previous study (Table
3). Reviewing the patient charts verified that those who did not return for the follow-up investigation had a similar outcome. Our 12.8% retreatment rate at 2 years is reasonable and within range of prior reports though somewhat higher than the 7.5% retreatment rate reported for LIFT at 2 years [
22,
27]. Of the 11 men requiring retreatment, 5 (45%) were within the 33 classified as severely obstructed 2 with baseline retention and 3 with PVR > 300 ml). A potential important take away from the retreated patients (2 PUL; 9 TURP) may be that, with PUL, “bridges are not burned”, because the PUL procedure does not preclude future BPH therapy, including TURP or further retreatment with PUL. All follow-up retreatments were conducted without incident or complication.
As might be expected when treating men with severe obstruction, one patient did not respond to either PUL or even later with TURP and remains on a suprapubic catheter due to detrusor decompensation. In a larger, less severely obstructed cohort, Roehrborn demonstrated PUL durability of 86% at 4 years [
27]. Sonksen et al. reported that, while 1-year retreatment for PUL and TURP were 7 and 6%, respectively, if treatment for complications were included, overall re-intervention for TURP rose to 14% [
24].
Preservation of sexual function observed in these patients was consistent with previous studies focusing on possible sexual side effects following PUL [
24,
28]. Our results indicated no procedure-related impotence or onset of ejaculatory dysfunction. In fact, in our evaluation, 3 of 11 patients (27%) with preoperative ejaculatory dysfunction reported improvement following PUL.
Late-stage LUTS
Prior clinical studies have demonstrated that PUL is an efficacious treatment for men with moderate to severe symptoms (IPSS > 12), suppressed urinary flow (Qmax ≤ 12 or 15 ml/s) and low residual volume (PVR ≤ 250 ml). [
21‐
24,
28]. This investigation shows that PUL may also be appropriate for men with later stage prostatic obstruction, as defined by urinary retention, elevated PVR or larger prostate. Fourteen patients presented with in-dwelling urinary catheterization (1–3 months with unsuccessful trial to void). Twelve (86%) men in urinary retention were successfully weaned from their catheters and remained catheter-free at the last follow-up. One of the two treatment failures also failed to void after follow-up with TURP, resulting in chronic suprapubic catheterization. Three of the seven patients with high PVR at baseline underwent TURP. Our initial experience suggests that PUL should be reserved for patients with functioning bladders. If a patient presents with very high PVR, we would recommend a period of catheterization to stabilize his bladder function and an urodynamic evaluation.
Comparison with TURP and LASER
The BPH6 randomized study compared PUL and TURP showed that TURP offers modestly greater IPSS improvement and much greater Qmax improvement, but interestingly, there was no significant difference regarding improved quality of life [
24]. While BPH6 study was of a modest size, the results for TURP mirrored those of the recent larger study of TURP and LASER [
7]. In the current study, the Qmax rose modestly to a mean of 14.4 ml/s. Berges and Oelke showed in a study of 1763 German men that the Qmax represents a normal flow for this age group; thus, PUL does not give the flow correlated to TURP, but may simply improve flow characteristics to patients satisfaction [
29]. As this modest Qmax improvement was associated with 51, 52, and 70% improvements in IPSS, QOL, and PVR, it may be that larger Qmax increases are not necessary for all patients to achieve an acceptable result.
Because this investigation is not a randomized prospective study comparing the extended inclusion criteria, it may be considered a limitation of the study. However, by comparing this investigation to the available surgical treatment options that are currently available, we have to keep in mind that those options are in a constant state of flux.