Triple treatment of high-risk prostate cancer. A matched cohort study with up to 19 years follow-up comparing survival outcomes after triple treatment and treatment with hormones and radiotherapy.

Purpose: To evaluate the efficacy of a triple treatment strategy, including surgery, on high risk prostate cancer comparing long-term survival outcome with a cohort receiving standard radiotherapy with endocrine therapy. Materials and methods: This study compared two cohorts in survival outcomes, matched on the year of diagnosis and age. In both groups there was a curative intention to treat localized high-risk prostate cancer (one or more of Gleason score 8-10, PSA 20-50 or stage T3), diagnosed between 1995-2010, follow-up at the end of 2014. Triple treatment group: 153 patients treated primarily with radical prostatectomy with neoadjuvant endocrine treatment, and a majority with adjuvant radiotherapy. Standard radiotherapy group: 702 patients with a treatment of either external radiotherapy or high dose brachytherapy combined with external beam therapy, both modalities in combination with neoadjuvant endocrine therapy. Results: The prostate-cancer-specific mortality was 10% for the triple treatment group and 15% for the standard radiotherapy group during the period, HR = 2.01 (1.17-3.43), p = 0.011. The corresponding overall mortality was 26% vs 29%, HR = 1.54 (1.09-2.17), p = 0.015. High Gleason score was the dominating risk factor for early death due to the disease. Clinical T-stage was not an independent risk factor for death in this population. Conclusion: Adding surgery in a multimodal treatment model in high-risk prostate cancer showed significantly better survival outcome compared with the current standard of radiotherapy. Surgery in this group is, therefore, compelling and that also includes a clinical T3-stage of the disease. The study is limited by possible selection bias for the two treatment models.

A new technique of bladder neck reconstruction during radical prostatectomy in patients with prostate cancer.

PURPOSE: To evaluate continence after radical prostatectomy in prostate cancer patients, in whom a new method of the bladder neck reconstruction (BNR) using deep dorsal stitch was implemented (deep single stitch through all bladder layers directly dorsal to the bladder opening after ″ tennis racket″ reconstruction) and to provide justification for its use by means of anatomical study in cadavers. MATERIAL AND METHODS: Open radical retropubic prostatectomy was performed in 84 patients: 39 patients with a new BNR method used to improve continence and control group of 45 patients with standard ″tennis racket″ BNR. Median follow-up was 14 months in control group and 12 months in study group. Continence recovery was accessed early postoperatively and every 3 months thereafter. Anatomical study was performed on 2 male fresh cadavers reproducing two different BNR techniques to clarify any underlying continence related mechanisms. RESULTS: Patients with new BNR achieved full continence significantly faster (p=0.041), but the continence rates after 12 months were similar between groups. The severity of incontinence up to month 9 was significantly reduced in BNR group. The anastomotic stricture rate was not affected. Applying new BNR to the cadaver model revealed effects on early continence, namely presence of proximal passive closure mechanism in area of bladder neck. CONCLUSIONS: Continence in patients with the new BNR method using deep dorsal stitch recovered significantly faster. Moreover, a reduced grade of residual incontinence was documented. The effect was non-significant at month 12 of follow-up, meaning that only early effect was present.

A new technique of bladder neck reconstruction during radical prostatectomy in patients with prostate cancer

To evaluate continence after radical prostatectomy in prostate cancer patients, in whom a new method of the bladder neck reconstruction (BNR) using deep dorsal stitch was implemented (deep single stitch through all bladder layers directly dorsal to the bladder opening after “tennis racket” reconstruction) and to provide justification for its use by means of anatomical study in cadavers.

Long-term follow-up after triple treatment of prostate cancer stage pT3.

OBJECTIVE: Radical prostatectomy (RP) has become the most common treatment for localized prostate cancer in Sweden. Outcome is extremely good for pT2 stage with Gleason score 6 or less, but more than every fourth operated patient will have a pT3 stage on full amount specimen histology. According to several reports the risk of biochemical recurrence is quite high, especially in stage pT3, on active surveillance after surgery alone. In 1994 the authors recognized this fact at their clinic and decided to apply a new multimodality treatment concept. MATERIAL AND METHODS: During 10 years, between 1 January 1995 and 1 January 2005, 98 pT3 patients were treated with a triple treatment: 8 months of neoadjuvant/adjuvant luteinizing hormone-releasing hormone (LH-RH) analogue treatment, RP and immediate adjuvant radiotherapy (RT) 3 months after RP. RT was delivered to 60 Gy in 30 fractions to the prostatic bed to all the patients. The cumulative risk of progression was calculated with the Kaplan-Meier method. The impact of risk factors was evaluated by the Cox proportional hazard model. RESULTS: Ninety-eight (74 pT3a and 24 pT3b) patients were followed with a mean observation time from operation until October 2007 of 71.6 (median 65.5, range 35-146) months. The mean follow-up time to biochemical failure, death or last measurement of prostate-specific antigen (PSA) was 57.8 (median 57.0, range 3-132) months. Fifteen patients out of 98 had experienced biochemical failure. Only Gleason score had an independent impact on the risk of PSA progression. Complications were mild and temporary and no serious adverse events were registered. CONCLUSIONS: Patients with locally advanced prostate cancer have a high risk of progression after RP as single therapy. Postoperative RT has been shown to improve the outcome. Neoadjuvant/adjuvant hormonal therapy has been shown to improve the outcome after RT. Bringing this knowledge together offering a multimodality therapy with neoadjuvant/adjuvant hormonal therapy, RP followed by postoperative immediate RT seems to offer a high chance of biochemical-free survival.

Transurethral resection of the prostate after intraprostatic injections of mepivacain epinephrine: a preliminary communication.

OBJECTIVE: Transurethral resection of the prostate (TURP) has been the gold standard for treatment of obstructive benign prostatic hyperplasia since the 1970s. Intraprostatic injections of mepivacain epinephrine (ME) (Carbocain-Adrenalin) before Core Therm (Prostalund feedback treatment) have been used to anaesthetize the gland and reduce the intraprostatic blood flow, thereby reducing discomfort, treatment time and energy consumption during transurethral microwave thermotherapy. As a result of this experience, use of this technique before TURP, to reduce perioperative bleeding and blood loss during TURP surgery, was investigated. This paper presents the author's first clinical experiences using the Schelin Catheter to add intraprostatic infiltrations of ME before TURP. MATERIAL AND METHODS: Eleven consecutive TURP operations were performed immediately after intraprostatic injections of 0.5% ME. Altogether, 20 ml was injected and infiltrated into the two quadrants (8 and 11 o'clock) in the right lobe using the Schelin Catheter technique. Then the right lobe was resected using a modified Nesbit technique. To avoid washout of epinephrine another 20 ml of 0.5% ME was then infiltrated in the left lobe (1 and 4 o'clock) just before resection of the left lobe. Total blood loss, bleeding per gram of resected tissue and operating time were compared with a reference group of 30 consecutive TURP operations, without any intraprostatic injections, performed by the same urologist. All patients (both groups) had spinal anaesthesia according to the hospital routine. RESULTS: In the 11 patients receiving intraprostatic ME before TURP mean total blood loss was 108 ml (<20-302 ml), mean bleeding/g resected tissue was 4.8 ml (0-8.3 ml) and the mean operating time was 2.0 min/g (1.5-3.0 min) Mean resected volume was 21.3 g (15-37 g). In the reference group mean total blood loss was 354 ml (67-1500 ml), mean bleeding/g resected tissue was 15.4 ml (5.9-44.4 ml) and operating time was 2.2 min/g. Mean resected volume was 23.6 g (5-54 g). All patients in the ME group underwent postoperative self-irrigation by diuretics without any signs of latent bleeding. One late recurrent bleeding was registered in the ME group. CONCLUSIONS: These first clinical experiences indicate several possible benefits when using prostate infiltrations of ME immediately before TURP, such as significantly less perioperative bleeding and total blood loss. Reduced operation time, improved visibility, improved safety, facilitated education, increased achievable resection volumes and complete resections are also possible benefits.

Five-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study.

OBJECTIVES: To compare the efficacy and safety of transurethral microwave thermotherapy (TUMT) with ProstaLund Feedback Treatment, using the CoreTherm device, with transurethral resection of the prostate (TURP) 5 years after treatment. METHODS: This prospective, randomized, multicenter study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to TUMT or TURP in a 2:1 ratio. Patients were followed up at 3, 6, 12, 24, 36, 48, and 60 months after treatment. The intermediate results at 12 and 36 months have been previously reported. The treatment outcome at 5 years was evaluated with the International Prostate Symptom Score (IPSS), quality of life question (QOL), peak urinary flow rate (Qmax), postvoid residual urine volume, and prostate volume. The CoreTherm device differs from other microwave devices in that the intraprostatic temperature is constantly measured during the procedure to guide the treatment. RESULTS: Of the 154 patients, 66% completed the 60 months of follow-up. Statistically significant improvements in the TUMT and TURP groups were observed for IPSS, QOL, and Qmax at 60 months. The average values for the TUMT group were an IPSS of 7.4, QOL score of 1.1, and Qmax of 11.4 mL/s. The values for the TURP group were IPSS of 6.0, QOL score of 1.1, and Qmax of 13.6 mL/s. No statistically significant differences were found in any of these variables between the two treatment groups. In the TUMT group, 10% needed additional treatment versus 4.3% in the TURP group. CONCLUSIONS: The clinical outcome 5 years after TUMT using the CoreTherm device was comparable to the results seen after TURP. The safety of TUMT using the CoreTherm device compared favorably with that of TURP.

Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention: a prospective, randomized, controlled, multicenter study.

OBJECTIVES: To assess the clinical efficacy of ProstaLund Feedback Treatment (PLFT) using the CoreTherm device versus transurethral resection of the prostate (TURP) and prostate enucleation surgery. METHODS: We performed a prospective, randomized, controlled, multicenter study of 120 patients with symptomatic benign prostatic hyperplasia and persistent urinary retention requiring an indwelling catheter or clean intermittent catheterization. The primary efficacy variables were success in catheter removal and symptom improvement. RESULTS: Of the 120 patients, 79% and 88% were catheter free after PLFT and surgery, respectively. The bother score (quality-of-life question) decreased from 4.6 in both groups before treatment to 1.4 in the PLFT group and 0.8 in the surgery group at 6 months of follow-up. The peak urinary flow rate was 13.4 mL/s after PLFT and 18.0 mL/s after surgery. The mean catheterization time was 34 days in the PLFT group and 5 days in the surgery group. CONCLUSIONS: PLFT is an effective alternative to surgical treatment in this group of catheterized patients. The risk of severe complications is reduced using PLFT, and an excellent treatment option can thereby be offered to this high-risk patient group who earlier could be treated only with lifelong catheterization.

Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: a prospective randomized multicenter study.

OBJECTIVES: To compare, in a prospective randomized multicenter study, the efficacy and safety of transurethral microwave thermotherapy with ProstaLund Feedback Treatment (PLFT), using the CoreTherm device, with transurethral resection of the prostate (TURP) 36 months after treatment. METHODS: The study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to PLFT or TURP in a 2:1 ratio. The treatment outcome was evaluated on the basis of the International Prostate Symptom Score (IPSS), the quality-of-life question (QOL) of the IPSS, peak urinary flow rate (Qmax), urodynamics, and adverse events. The microwave power and treatment time were adjusted according to each patient's response to the supplied energy (ie, the intraprostatic temperature guided the PLFT). RESULTS: Statistically significant improvements in both the TURP and the PLFT groups were observed for IPSS, QOL, and Qmax at 36 months. The average value for the PLFT group was 8.2, 1.2, and 11.9 mL/s for IPSS, QOL, and Qmax, respectively. The corresponding values for the TURP group were IPSS 5.0, QOL 1.0, and Qmax 13.5 mL/s. The difference in IPSS outcome was statistically significant; however, no statistically significant differences were found in QOL or Qmax between the two treatment groups. The degree of improvement was in the same range as that observed after 12 and 24 months for both groups. During the 12 to 36-month period, the most frequent adverse events in the TURP group were impotence (15%), micturition urgency (13%), and urethral disorder (8%); in the PLFT group, impotence (8%), prostate-specific antigen increase (5%), and hematuria (4%) were the most common. CONCLUSIONS: The clinical outcome 3 years after microwave thermotherapy with PLFT was comparable to the results seen after TURP. The safety of PLFT compared favorably to that of TURP in this study.

Evaluation of microwave thermotherapy with histopathology, magnetic resonance imaging and temperature mapping.

PURPOSE: Interstitial temperature mapping was used to determine the heat field within the prostate by the Coretherm (ProstaLund, Lund, Sweden) transurethral microwave thermotherapy device. Gadolinium enhanced magnetic resonance imaging (MRI) and histopathology were used to determine the extent and pattern of coagulation necrosis following treatment. The cell kill assessment feature of the device was compared with MRI and histopathology. MATERIALS AND METHODS: A total of 12 patients were treated, including 5 with adenocarcinoma of the prostate and 7 with benign prostatic hyperplasia. Temperature sensors were inserted from the perineum to map the temperature distribution. The 5 patients with adenocarcinoma underwent prostatectomy and subsequent histopathology 3 to 6 weeks after treatment. MRI and cell kill calculations were performed in all patients. RESULTS: Therapeutic temperatures were found in a bowl-like shape with a wide circumference of highest temperatures at the base of the prostate, and decreasing temperature and circumference toward the apex. Tissue necrosis assessed by histopathology, MRI and cell kill calculations overlapped reasonably well in shape and size. Histopathology showed that the prostatic urethra was destroyed by treatment. CONCLUSIONS: Coretherm microwave treatment causes significant tissue necrosis of the prostate, bladder neck and urethral mucosa. The cell kill calculation provides an on-line estimate of the amount of necrosis caused during treatment.

Effects of intraprostatic and periprostatic injections of mepivacaine epinephrine on intraprostatic blood flow during transurethral microwave thermotherapy: correlation with [15O]H2O-PET.

BACKGROUND AND PURPOSE: Experiences with the ProstaLund Feedback Treatment (PLFT) with the CoreTherm device and results from a previous positron emission tomography (PET) study suggest that the intraprostatic blood flow increases considerably during treatment in response to heat exposure. Early results with intraprostatic injection of mepivacaine epinephrine prior to PLFT have indicated greater patient comfort during treatment and shorter treatment time secondary to lower intraprostatic blood flow. In this pilot study, the effect of intraprostatic injection of mepivacaine epinephrine on intraprostatic blood flow before and during PLFT was evaluated by PET using [15O]H2O. PATIENTS AND METHODS: In four patients scheduled for PLFT, a baseline value of the intraprostatic blood flow was established using [15O]H2O-PET. Thereafter, intraprostatic injections of mepivacaine epinephrine were given using a prototype of the Schelin Catheter. In two of the patients, PET was performed immediately after the mepivacaine epinephrine injections and 10 and 24 minutes after the start of PLFT. To reduce the risk of wash-out of the drug, the next two patients were examined 7 and 17 minutes after the start of PLFT but not in connection with the anethetic injection. RESULTS: In patients 1 and 2, mepivacaine epinephrine decreased the prostatic blood flow. During PLFT, there was a slight increase in blood flow in patient 1 and a more pronounced increase in patient 2. In patient 3, the blood flow during treatment was almost unchanged, while it decreased in patient 4. CONCLUSIONS: Intraprostatic injection of mepivacaine epinephrine may reduce, or even eliminate, the increase in blood flow that is usually seen during PLFT. The vague effect seen in patients 1 and 2 may be explained by wash-out of the drug.

Feedback microwave thermotherapy versus TURP for clinical BPH--a randomized controlled multicenter study.

OBJECTIVES: To compare the outcome of a microwave thermotherapy feedback system that is based on intraprostatic temperature measurement during treatment (ProstaLund Feedback Treatment or PLFT) with transurethral resection of the prostate (TURP) for clinical benign prostatic hyperplasia (BPH) in a randomized controlled multicenter study. The safety of the two methods was also investigated. METHODS: The study was performed at 10 centers in Scandinavia and the United States. A total of 154 patients with clinical BPH were randomized to PLFT or TURP (ratio 2:1); 133 of them completed the study and were evaluated at the end of the study 12 months after treatment. Outcome measures included the International Prostate Symptom Score (IPSS), urinary flow, detrusor pressure at maximal urinary flow (Qmax), prostate volume, and adverse events. Patients were seen at 3, 6, and 12 months. Responders were defined according to a combination of IPSS and Qmax: IPSS 7 or less, or a minimal 50% gain, and/or Qmax 15 mL/s or greater or a minimal 50% gain. RESULTS: No significant differences in outcome at 12 months were found between PLFT and TURP for IPSS, Qmax, or detrusor pressure. The prostate volume measured with transrectal ultrasonography was reduced by 30% after PLFT and 51% after TURP. Serious adverse events related to the given treatment were reported in 2% after PLFT and in 17% after TURP. Mild and moderate adverse events were more common in the PLFT group. With the criteria mentioned above, 82% and 86% of the patients were characterized as responders after 12 months in the PLFT and TURP groups, respectively. The post-treatment catheter time was 3 days in the TURP group and 14 days in the PLFT group. CONCLUSIONS: The outcome of microwave thermotherapy with intraprostatic temperature monitoring was comparable with that seen after TURP in this study. From both a simplicity and safety point of view, PLFT appears to have an advantage. Taken together, our findings make us conclude that within a 1-year perspective microwave thermotherapy with PLFT is an attractive alternative to TURP in the treatment of BPH.

Mediating transurethral microwave thermotherapy by intraprostatic and periprostatic injections of mepivacaine epinephrine: effects on treatment time, energy consumption, and patient comfort.

BACKGROUND AND PURPOSE: Profound intraprostatic blood flow may complicate reaching a therapeutic temperature in the prostate during transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia (BPH). A retrospective survey is presented describing the effect of intraprostatic and periprostatic administration of mepivacaine epinephrine on treatment time, intraprostatic blood flow, energy delivery, and patient comfort. PATIENTS AND METHODS: Fifteen consecutive obstructed patients with lower urinary tract symptoms attributable to BPH received TUMT (ProstaLund Feedback Treatment). In order to improve patient comfort, injections of 10 mL of 0.5% mepivacaine epinephrine were administered in three locations into the prostate prior to treatment. The results were compared with those of a reference group consisting of 35 consecutive patients who had received ProstaLund Feedback Treatment without administration of mepivacaine epinephrine. RESULTS: Patients who received intraprostatic mepivacaine epinephrine had a shorter treatment time (32+/-9 minutes v 61+/-6 minutes), required less energy (65+/-27 kJ v 172+/-32 kJ), and had a lower calculated intraprostatic blood flow (13+/-5 units/minute v 26+/-12 units/minute) than the reference group. Patients receiving mepivacaine epinephrine also required less analgesic medication during the treatment. The clinical outcome in terms of symptom scores and peak uroflow rates appeared to be similar for the two groups. CONCLUSION: Intraprostatic injection of mepivacaine epinephrine prior to TUMT seems to have beneficial effects. It may represent an important improvement of thermotherapy and enable successful treatment of those patients who previously failed secondary to a profound intraprostatic blood flow.