Circulating tumour cells to drive the use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.

BACKGROUND: Guidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld. PATIENTS AND METHODS: The CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%). RESULTS: A total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (N = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality [hazard ratio (HR) 1.61, 95% CI 1.05-2.45, P = 0.03] and disease relapse (HR 1.87, 95% CI 1.28-2.73, P = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48). CONCLUSION: The absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC. TRIAL REGISTRATION: Netherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954.

Influence of decay of laser fibers during laser prostatectomy on clinical results.

Three types of sidefiring laser fibers (34 Urolase, 20 Ultraline, and 114 Prolase II) were visually inspected after a laser prostatectomy, and transmission measurements were performed using a power meter (Aquarius). The results were correlated with the clinical outcome. Despite differences in the amount of loss in transmission for the fibers used, we could not establish any significant effect on clinical outcome measures, such as improvement in maximal flow rate or symptom score. The visual aspect of the Urolase fibers was significantly related to the amount of transmission loss, whereas no such relation was found for the other two types of fibers. Prostate size and the total amount of energy delivered by the laser source also did not correlate with the clinical outcome. To determine the relation between the energy absorbed by the prostate and clinical outcome, a large number of patients must be evaluated, and any factor that can be controlled needs to be monitored. For the latter, the power meter as presented here is a useful complementary tool.

Quality-of-life assessment in patients after laser prostatectomy.

OBJECTIVE: To determine the importance of the assessment of quality of life in patients who have undergone laser prostatectomy. PATIENTS AND METHODS: Patients undergoing laser prostatectomy were evaluated using the International prostate symptom score (IPSS) questionnaire, uroflowmetry, post-void residual volume (PVR) measurements, and quality-of-life (QOL) and sexual function questionnaires. RESULTS: In all, 103 patients were evaluated; there was an overall significant improvement in the mean IPSS, maximum flow, PVR and QOL score and no apparent subjective change in sexual function. There was a good correlation between the IPSS and the QOL score, but no correlation between the QOL score and the maximum flow rate, and only a weak correlation between the IPSS and the maximum flow rate. CONCLUSION: Laser prostatectomy significantly changed the patients' quality of life. This may be more important for the patient than the improvement in the voiding variables alone. In future (changes in) quality of life will probably contribute significantly to selecting patients with voiding complaints for particular treatments.

Laser treatment of the prostate using the Urolase fiber: the Dutch experience.

PURPOSE: Subjective and objective results were assessed after laser prostatectomy with the Urolase fiber at 5 different centers in The Netherlands. MATERIALS AND METHODS: Patients were evaluated with the international prostatic symptom score questionnaire, uroflowmetry and post-void residual volume measurements. Urodynamic investigations with pressure-flow analysis were performed at 2 centers. RESULTS: Data for 233 patients were evaluated. Overall significant improvement in mean international prostatic symptom score, maximum flow, post-void residual and urodynamic parameters was noted. Differences in outcome among the centers may be due to variation of technique or different selection criteria. Postoperative morbidity was significant, with irritative voiding complaints for 4 to 6 weeks in up to 50% of all patients and urinary tract infections in 21.1%. CONCLUSIONS: Laser prostatectomy results in subjective and objective improvement, which is operator independent. Despite the observation that perioperative (intraoperative and immediate postoperative) morbidity seems less severe compared to transurethral resection of the prostate, there is a shift toward greater postoperative morbidity.

Variation in output power of laser prostatectomy fibers: a need for power measurements.

OBJECTIVES: The aim of this study was the assessment of the quality of side-firing fibers that are being used for laser prostatectomy, either by a laser light transmission measurement or by visual inspection. METHODS: A power meter (Aquarius) was developed to measure the actual power transmitted through a side-firing fiber and delivered to the prostatic tissue. The power measurements were performed under clinical conditions, that is, under water and at relatively high input power. Furthermore, a protocol was developed for visual inspection of the fibers. Eight types of side-firing fibers were measured before use. Before and after a procedure, three fiber types were measured: ProLase II (28 samples), UltraLine (23 samples), and UroLase (44 samples). All these fibers were used in standard treatment protocols. RESULTS: At 60 W the transmission of new fibers (not used) ranged between 49% and 83% when compared to a bare fiber. After use, a large variation was found in transmitted power between different samples of one device. A correlation with total transmitted power was not present. At higher power input, vapor bubbles are generated at the tip of the fibers. Depending on the fiber design, these bubbles have a major impact on the transmission. Only for the UroLase fiber was there a significant correlation between visual inspection and the transmission of used samples at 10, 20, and 40 W. CONCLUSIONS: The transmission strongly varies between fibers and between different samples of one fiber during clinical use. Moreover, the transmission does not correlate with visual inspection. A power measurement during a clinical treatment will contribute to a more controlled procedure and to a better comparison of clinical laser prostatectomy studies.

Urinary tract infections following laser prostatectomy: is there a need for antibiotic prophylaxis?

OBJECTIVE: To evaluate the incidence of urinary tract infections (UTIs) after transurethral laser therapy of the prostate and the need for peri-operative antibiotics. PATIENTS AND METHODS: One-hundred and sixteen patients (mean age 65 years, range 51-85) with benign prostatic enlargement (BPE) were treated with a Nd:YAG laser, using either the TULIP device, the Urolase fibre or the Ultraline fibre. The incidence of voiding complaints, UTIs and the need for catheterization after treatment were assessed. The first 43 patients (Group I) received no antibiotics perioperatively and the next 73 patients (Group II) received co-trimoxazole for 5 days. RESULTS: The patients treated using the TULIP device had more urinary complaints after treatment than those treated using the Ultraline and Urolase fibres. In Group I, 48% of the patients developed a UTI and in Group II the incidence of UTIs decreased to 30% after treatment. The incidence of UTIs was unrelated to the procedure performed. Although not statistically significant, peri-operative antibiotics tended to reduce the incidence of UTIs. Prolonged catheterization was correlated with the incidence of UTI. In Group I, patients who were treated using the Ultraline procedure had their catheter removed after a mean of 24 days, compared with 21 days for those treated with the Urolase and 19 days with the TULIP device. In Group II, the patients needed catheterization for a mean of 17 days following Ultraline treatment and 16 days following the Urolase procedure. CONCLUSIONS: Antibiotic prophylaxis tended to decrease the incidence of post-treatment UTIs. However, there was no clear association between the presentation and duration of complaints and the presence of UTIs.

Lasers in the treatment of benign prostatic obstruction: past, present, and future.

Lower urinary tract symptoms caused by benign prostatic obstruction (BPO) has been, and still is, treated by performing a transurethral or open prostatectomy. During the last decade many alternative treatments have been introduced and one of these new modalities uses laser energy in the ablation of prostatic tissue. When reviewing the literature on laser treatment of the prostate using side-firing laser devices, this procedure has proven to be safer and almost as effective as transurethral resection of the prostate (TURP). But although severe complications as TURP syndrome, incontinence and the need for blood transfusions have not occurred during laser prostatectomies, morbidity consisting of irritative voiding compliants and long catheterization duration have been reported by several authors. With the development of the contact laser probe and the interstitial laser technique some of these problems are (partly) solved, but also these new techniques still have considerable limitations which may disappear with future developments of newer laser probes and refining of existing laser techniques. Also, a better understanding and control in the laser-tissue interaction may help in reducing morbidity and inducing a more effective treatment.

Urodynamic assessment in the laser treatment of benign prostatic enlargement.

OBJECTIVE: To determine if bladder outlet obstruction can be adequately relieved after laser prostatectomy. PATIENTS AND METHODS: Since November 1992, a total of 105 patients underwent laser treatment of the prostate because of complaints related to benign prostatic enlargement (BPE). To date, urodynamic data from a study of pressure flow analysis are available for 79 patients both at baseline and at 6 months after treatment. Patients were evaluated using changes in symptoms (IPSS symptom score), peak flow rate (Qmax), post-voiding residual volume (PVR), detrusor pressure at maximum flow (Pdet at Qmax), and the linear passive urethral resistance relation (LPURR). Moreover, patients with minimal bladder outlet obstruction were compared to patients with severe bladder outlet obstruction. RESULTS: There was a significant improvement in mean IPSS score from 21.3 at baseline to 5.3 at the 6-month follow-up. The Qmax improved from 7.9 mL/s to 17.8 mL/s, and the PVR decreased from 91.6 mL to 15.6 mL. At baseline, > 80% of the patients were considered obstructed according to the analysis of pressure flow, whereas 6 months after laser treatment, only 5% of the patients were still considered obstructed. A comparison of the outcome between minimally obstructed patients and severely obstructed patients showed comparable improvements. CONCLUSION: Laser therapy of the prostate was, according to urodynamic parameters, capable of relieving outlet obstruction and minimally obstructed patients also showed a significant relief of outlet obstruction.

Urodynamic results of laser treatment in patients with benign prostatic hyperplasia. Can outlet obstruction be relieved?

PURPOSE: A urodynamic study was done to judge the capability of laser treatment to relieve bladder outlet obstruction. MATERIALS AND METHODS: Advanced urodynamic studies with pressure-flow analysis were performed before and 6 months after laser treatment using 3 different laser devices. RESULTS: Forty patients showed significant improvement in all obstruction parameters (detrusor pressure at maximum flow rate, urethral resistance relation, theoretical cross-sectional urethral area, minimal detrusor pressure and linear passive urethral resistance relation) together with significant subjective improvement in international prostate symptom score. After treatment 82 to 92% of the patients could no longer be considered to have obstruction. No difference in outcome among the devices used was found. CONCLUSIONS: Laser prostatectomy is indeed capable of relieving bladder outlet obstruction.

Durability of laser fibers.

In 90 patients treated with laser prostatectomy using the Urolase (n = 50) or Ultraline (n = 40) laser fiber, the fiber-tip durability was investigated. In general the Urolase fiber tips were less damaged than the Ultraline fiber tips. At visual inspection, 62% of the Urolase fiber tips were graded as minimally damaged in comparison with 28% of the Ultraline group. The Urolase fiber tips are more susceptible than the Ultraline fiber tips to damage caused by tissue contact, whereas the latter seem more fragile. Transmission measurements were performed in a laboratory setting to estimate the loss of energy output at the fiber tip due to damage. These measurements showed a major loss in almost all fibers. None of the Ultraline fibers had less than 10% transmission loss, and 18% of the Urolaser fibers had a transmission value of more than 90%. Finally, there seemed to be a poor correlation between the visual aspects of the fibers used and the changes in transmission.

Experience with the Ultraline and Urolase laser fibers: is there any difference?

Laser treatment of benign prostatic hyperplasia has enjoyed growing popularity among urologists over the last few years. Various applicators and techniques have been reported. Because this may result in a different overall performance, we performed a prospective randomized study comparing the results of treatment using the Ultraline fiber (n = 44) with that using the Urolase fiber (n = 49). Although different types of fibers and techniques were used, the results of this study were surprisingly similar for both fibers used. The uroflow for the Ultraline group increased from an average of 7.9 ml/s at baseline to 19.3 ml/s at 3 months and 16.9 ml/s at 6 months. In the patients treated with the Urolase fiber the uroflow improved from an average of 7.8 ml/s at baseline to 19.5 and 16.3 ml/s at 3 months and 6 months, respectively. The improvement in symptoms, reflected by changes in the I-PSS symptom scores, for the Ultraline group went from 21.0 at baseline to 7.9 at 3 months and 6.0 at 6 months. The Urolase patients improved from 21.0 at baseline to 8.2 and 5.6 at 3 and 6 month, respectively. The morbidity mainly consisted of a prolonged need for posttreatment catheterization and irritative symptoms lasting for about 2-4 weeks. From this study we conclude that the results achieved by laser treatment of the prostate using the Ultraline and Urolase fibers are both equivocal and excellent; however, the morbidity of these treatments remains considerable.