Ferruh Zorlu

The Effect of Repeat Transurethral Resection on Recurrence and Progression Rates in Patients With T1 Tumors of the Bladder Who Received Intravesical Mitomycin: A Prospective, Randomized Clinical Trial

PURPOSE We compared the outcomes of repeat transurethral resection plus intravesical mitomycin C with initial transurethral resection of bladder plus intravesical MMC in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder in terms of recurrence, progression and overall survival. MATERIALS AND METHODS Of 148 newly diagnosed patients with T1 bladder cancer 142 were prospectively randomized in 2 groups between January 2001 and January 2005. A total of 74 patients underwent second TURB and received adjuvant MMC intravesically (group 1) and 68 patients received adjuvant MMC following the initial TURB (group 2). All repeat TURB operations were performed 2 to 6 weeks following initial TURB. Patients with incomplete resection, Cis or muscle invasive disease were excluded from study. The first dose of mitomycin C (40 mg per week for a total of 8 weeks) was instilled intravesically in all patients during the first 24 hours after the last surgery. RESULTS Mean followup was 31.5 months (range 6 to 48) with no difference between the 2 groups. The rate of recurrence-free survival was 86.35% (SE 0.4%), 77.67% and 68.72% in group 1, and 47.08%, 42.31% and 37.01% in group 2 for the first, second and third year, respectively (overall 74.32% vs 36.76%, log rank 0.0001). Recurrence was observed in 19 of the 74 (25.68%) patients in group 1 and in 43 of the 68 (63.24%) patients in group 2. Ten of the 19 (52.63%) patients in group 1 and 35 of the 43 (81.39%) patients in group 2 had recurrence within 12 months. Recurrence was observed in 17.6%, 25% and 60% of patients with G1, G2 and G3 tumors, respectively, in group 1. The same rates for group 2 were 25%, 64% and 90%. The RFS rate was significantly worse in the high grade group (G2 and G3) (p <0.001). Progression was observed at 4.05% for group 1 compared to 11.76% for group 2 (log rank 0.0974). OS was 91.89% and 89.71% in group 1 and 2, respectively (log rank 0.732). CONCLUSIONS The high recurrence rate in patients who did not undergo ReTUR is due to a high residual tumor rate following initial TURB. The benefit of ReTUR is especially true for high grade tumors. Since intravesical MMC was present in both groups, this study has shown that intravesical chemotherapy does not compensate for inadequate resection. Progression does not seem to be affected by ReTUR although there was a trend favoring the ReTUR group. We recommend ReTUR for patients with primary high grade T1 disease to achieve better recurrence-free survival.

Impact of Routine Second Transurethral Resection on the Long-Term Outcome of Patients with Newly Diagnosed pT1 Urothelial Carcinoma with Respect to Recurrence, Progression Rate, and Disease-Specific Survival: A Prospective Randomised Clinical Trial

BACKGROUND Transurethral resection (TUR) of bladder tumours is not only mandatory for adequate staging but also crucial in delaying or preventing tumour recurrence and progression. OBJECTIVE To evaluate the impact of routine second TUR on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS Two hundred ten newly diagnosed T1 bladder cancer patients were prospectively randomised to two groups between January 2001 and January 2005. Second TUR was performed within 2-6 wk after the initial resection for the patients of group 1. Second TUR was not done in group 2. All patients (groups 1 and 2) received the first instillation of intravesical chemotherapy within 24h after the initial resection. Urine cytology and follow-up cystoscopy were performed at 3-mo intervals for the first year, biannually for the second year, and annually thereafter. All patients were followed until death or a minimum of 54 mo. MEASUREMENTS This study recorded recurrence, progression rate, and disease-specific survival. RESULTS AND LIMITATIONS The mean follow-up period was 66.1 mo without a significant difference between the groups. Residual tumour was detected histopathologically in 35 of 105 patients in group 1. Of these patients, eight had upper-stage (pT2) disease. Recurrence was observed in 37 of the 93 patients in group 1 and 70 of the 98 patients in group 2. Median recurrence-free survival was 47 mo for group 1 compared with 12 mo for group 2. Progression was observed in 6.5% of patients for group 1 compared to 23.5% of patients for group 2 (p=0.001). Median progress-free survival was 73 mo for group 1 compared to 53.5 mo for group 2. The overall survival rate was 67.7% and 64.3% in groups 1 and 2, respectively (log-rank test result: 0.363). Only 5 of the 30 patients in group 1 died of cancer compared to 11 of the 35 patients in group 2 (p=0.038). CONCLUSIONS We have clearly shown that second TUR, which is performed only after complete first TUR, has significantly decreased the recurrence and progression rates in patients with newly diagnosed T1 disease compared to patients with T1 disease but with no second TUR. This study once more underscores the effect of TUR, which is usually underappreciated.

Is a Second Transurethral Resection Necessary for Newly Diagnosed pT1 Bladder Cancer

PURPOSE We evaluated the potential benefit of a second transurethral resection in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder. MATERIALS AND METHODS Between January 2001 and May 2003, 80 patients with stage T1 bladder cancer were included in this protocol in which all patients prospectively received second TUR within 2 to 6 weeks following the initial resection. Patients with incomplete resections were excluded from study. The pathological findings of the second TUR were reviewed. RESULTS Of the 80 patients who underwent second resection, 18 (22.5%) had macroscopic tumors before resection. However, with the addition of microscopic tumors, overall residual disease was determined in 27 (33.8%) patients. Of the 27 patients 7 had pTa, 14 had pT1, 3 had pT1+pTis and 3 had pT2 disease. Residual cancers were detected in 5.8%, 38.2% and 62.5% in G1, G2 and G3 tumors, respectively. The risk of residual tumor directly correlated with the grade of the initial tumor (p = 0.009). CONCLUSIONS Although second TUR dramatically changed the treatment strategy in a small percentage of cases, we strongly recommend performing second TUR in all cases of primary pT1 disease, especially in high grade cases.

Is Prophylactic Breast Radiotherapy Necessary in All Patients With Prostate Cancer and Gynecomastia and/or Breast Pain?

PURPOSE We investigated the efficacy of prophylactic radiotherapy for gynecomastia/breast pain induced by 150 mg bicalutamide in a prospective, randomized, multi-institutional trial. MATERIALS AND METHODS After definitive treatment for localized prostate cancer 125 patients were randomized to 12 Gy radiotherapy before bicalutamide as prophylactic radiotherapy (53) or bicalutamide only for nonprophylactic radiotherapy (72). The incidence of gynecomastia, breast pain and tenderness, and discomfort perceived by the patients was assessed by physical examination and direct questioning at 3, 6 and 12 months of followup. RESULTS At the end of 12 months the gynecomastia rate was 15.8% in the prophylactic group and 50.8% in the nonprophylactic group (p <0.001). On patient evaluation the breast enlargement rate was 34.4%. The severity of breast pain and tenderness was not different between the groups. The breast pain rate was 36.4% and 49.2% by 12 months in the prophylactic and nonprophylactic groups, and the rate of patients who felt discomfort from gynecomastia was 11.4% and 29.5%, respectively. CONCLUSIONS In this prospective study the incidence of gynecomastia was not as high as previously believed. Although prophylactic breast irradiation seemed to decrease the gynecomastia rate in patients on 150 mg bicalutamide, our study proves that not all patients need prophylaxis since only 52% were significantly bothered by gynecomastia. Thus, individual assessment is needed to select patients who need prophylactic radiation while on 150 mg bicalutamide.

Stage I Testicular Seminoma: Para-Aortic and Iliac Irradiation with Reduced Dose after Orchiectomy

Background and Purpose: Radiotherapy remains the treatment of choice for patients with stage I seminoma. The aim of this study is to report preliminary results of reduced dose radiotherapy to ipsilateral pelvic and para-aortic lymph nodes. Materials and Methods: Between February 1996 and December 2001, 53 patients with stage I testicular seminoma were treated with adjuvant radiotherapy after orchiectomy. The median age was 34 years (19–59 years). Four (7.5%) patients had a history of cryptorchidism. Eleven (20.8%) patients showed elevated β-human chorionic gonadotropin. All patients had a radical inguinal orchiectomy and histopathological analysis yielded classic seminoma in 47 (88.7%), spermatocytic in 5 (9.4%) and anaplastic in 1 (1.9%) patients. A total of 19.6–20 Gy in 1.8- to 2-Gy daily fractions was administered to the para-aortic and ipsilateral iliac lymphatics. Results: Median follow-up time was 42 months (12–77 months). One patient developed para-aortic lymph node recurrence at month 28 of the follow-up. Five-year overall and disease-free survivals were 100 and 98%, respectively. Only grade I–II of the Radiation Therapy Oncology Group acute gastrointestinal complications without any severe late toxicity was detected. Conclusion: Reduced dose radiotherapy seems to be as effective as higher doses in the management of stage I seminoma with an acceptable toxicity.

Visceral obesity: A new risk factor for stone disease

INTRODUCTION We examined the relationship between stone disease and the amount of visceral adipose tissue measured with unenhanced computed tomography (CT). METHODS We included 149 patients with complaints of flank pain and kidney stones detected by CT, from August 2012 to April 2013. In addition, as the control group we included 139 healthy individuals, with flank pain within the same time period, with no previous history of urological disease and no current kidney stones identified by CT. Patients were analyzed for age, gender, body mass index, amount of visceral and subcutaneous adipose tissue, and serum level of low-density lipoprotein and triglyceride. RESULTS There were no differences between groups in terms of gender and age (p = 0.27 and 0.06, respectively). Respective measurements for the stone and control groups for body mass index were 29.1 and 27.6 kg/m(2); for visceral fat measurement 186.0 and 120.2 cm(2); and for subcutaneous fat measurements 275.9 and 261.9 cm(2) (p = 0.01; 0.01 and 0.36, respectively). Using multivariate analysis, the following factors were identified as increasing the risk of kidney stone formation: hyperlipidemia (p = 0.003), hypertension (p = 0.001), and ratio of visceral fat tissue to subcutaneous fat tissue (p = 0.01). Our study has its limitations, including its retrospective nature, its small sample size, possible selection bias, and missing data. The lack of stone composition data is another major limitation of our study. CONCLUSION The ratio of visceral to subcutaneous adipose tissue, in addition to obesity, hyperlipidemia, and hypertension, was identified as an emerging factor in the formation of kidney stones.

Prostate Cancer Incidence in Turkey: An Epidemiological Study

BACKGROUND This study aimed to determine the incidence of prostate cancer in Turkey in a population-based sample, and to determine clinical and pathological characteristics of the cases. MATERIALS AND METHODS All newly diagnosed prostate cancer patients were included in this national, multi-centered, prospective and non- interventional epidemiological registry study conducted in 12 cities representing the 12 regions of Turkey from July 2008 to June 2009. The population-based sample comprised 4,150 patients with a recent prostate cancer diagnosis. RESULTS Age-adjusted prostate cancer incidence rate was 35 cases per 100,000 in Turkey. At the time of diagnosis, median age was 68, median PSA level was 10.0 ng/mL. Digital rectal examination was abnormal in 36.2% of 3,218 tested cases. Most patients had urologic complaints. The main diagnostic method was transrectal ultrasound guided biopsy (87.8%). Gleason score was ≤6 in 49.1%, 7 in 27.8% and >7 in 20.6% of the cases. There was a statistically significant positive correlation between serum PSA level and Gleason score (p=0.000). The majority of patients (54.4%) had clinical stage T1c. CONCLUSIONS This is the first population-based national data of incidence with the histopathological characteristics of prostate cancer in Turkey. Prostate cancer remains an important public health concern in Turkey with continual increase in the incidence and significant burden on healthcare resources.

Results of Intravesical Chemo-Hyperthermia in High-risk Non-muscle Invasive Bladder Cancer

PURPOSE To examine the effectiveness of mitomycin-C and chemo-hyperthermia in combination for patients with high-risk non-muscle-invasive bladder cancer. MATERIALS AND METHODS Between November 2011-September 2013, 43 patients with high-risk non-muscle-invasive bladder cancer undergoing adjuvant chemo-hyperthermia in two centers were evaluated retrospectively. Treatment consisted of 6 weekly sessions, followed by 6 sessions. Recurrence and progression rate, recurrence-free interval and side effects were examined. Analyzed factors included age, gender, smoking status, AB0 blood group, body mass index, T stage and grade, concominant CIS assets. The associations between predictors and recurrence were assessed using multivariate Cox proportional hazard analyses. RESULTS A total of 40 patients completed induction therapy. Thirteen (32.5%) were diagnosed with tumor recurrence. Median follow-up was 30 months (range 9-39). Median recurrence-free survival was 23 months (range 6-36). The Kaplan-Meier-estimated recurrence-free rates for the entire group at 12 and 24 months were 82% and 61%. There was no statistically significant difference between patient subgroups. Cox hazard analyses showed that an A blood type (OR=6.23, p=0.031) was an independent predictor of recurrence- free. Adverse effects were seen in 53% of patients and these were frequently grades 1 and 2. CONCLUSIONS Intravesical therapy with combination of mitomycin-C and chemohyperthermia seems to be appropriate in high-risk patients with non-muscle-invasive bladder cancer who cannot tolerate or have contraindications for standard BCG therapy.

Intravesical bacillus Calmette-Guérin versus chemohyperthermia for high-risk non-muscle-invasive bladder cancer

INTRODUCTION Patients with high-risk non-muscle invasive bladder cancer (NMIBC) need adjuvant intravesical treatment after surgery. Although bacillus Calmette-Guérin (BCG) is highly effective, new adjuvant treatments to decrease recurrences and toxicity have been studies. We performed a retrospective propensity score-matched study to compare the efficacy of BCG and chemohyperthermia (C-HT). METHODS We included 1937 patients diagnosed with bladder cancer between January 2004 and January 2014. The primary efficacy endpoint was recurrence-free interval. Patients treated with C-HT were matched with patients treated with BCG using propensity score-matched analysis. Cox-regression models were used to estimate the association between intravesical treatments and the presence of recurrence and progression. RESULTS Of the 710 patients treated with intravesical treatments, 40 and 142 were eligible for inclusion in C-HT and BCG groups, respectively. Following case matching, there were no differences in patient or tumour characteristics between treatment groups. The 2-year recurrence-free interval in C-HT and BCG groups were 76.2% and 93.9%, respectively (p = 0.020). C-HT treatment (hazard ratio [HR] 5.42; 95% confidence interval [CI] 1.11-26.43; p = 0.036) and high-grade tumour (HR 4.60; 95% CI 1.01-20.88; p = 0.048) are associated with an elevated odds of tumour recurrence. In multivariate Cox-regression analysis, there was no significant difference between C-HT and BCG in the odds of recurrence (p = 0.054). There were no differences in progression between C-HT and BCG. CONCLUSION C-HT is not as effective treatment as BCG in high-risk NMIBC patients who are BCG-naive. Although, there were no significant difference in the odds of recurrence, recurrence-free interval is significantly improved by the administration of BCG.

Is Percutaneous Nephrolithotomy Safe for Elderly Kidney Stone Patients

Introduction: As a minimally invasive surgical method, PNL displayed a great development in techniques as well as equipments in the course of time. A conservative approach is no longer accepted in the elderly kidney stone patient population. Percutaneous nephrolithotomy is indicated as an effective and safe treatment in all age groups. In this study, we present percutaneous nephrolithotomy results obtained from kidney stone patients aged 65 years and over. Materials and Methods: Based on the total PNL operations performed to 570 renal units in our clinic, age, gender, size, laterality and location of the kidney stone, body mass index and number of access were compared for the subjects who were divided into two groups as being over and under sixty-five years of age. Operative time, presence of complications, transfusion requirements, postoperative fever and stone-free rate were analyzed for the two groups. Results: There was no difference between the two groups in terms of gender, body mass index, stone burden, number of accesses and stone laterality. There was no statistically significant difference between two groups with regard to stone free rate, preoperative complication rate and the need for transfusion. The majority of the complications were pain, bleeding, urinary leakage, and postoperative fever. Conclusion: PNL is a technique used for many years with successful results in kidney stone disease. As a minimally invasive treatment, PNL is the gold standard approach for kidney stones, and an effective and reliable treatment modality for elderly patients too.