Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer.

PURPOSE/OBJECTIVE: Definitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT. MATERIAL/METHODS: This was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS. RESULTS: 117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5-89.2) and 46% (95% CI 36.5-57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%. CONCLUSION: Partial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Select screening in a specific high-risk population of patients suggests a stage migration toward detection of non-muscle-invasive bladder cancer.

BACKGROUND: More than 25% of bladder cancer (BC) cases are still muscle-invasive at first diagnosis. Screening is unproven to enable the detection of more non-muscle-invasive tumors. BC association with aristolochic acid nephropathy (AAN) was reported after intake of slimming pills containing Chinese herbs. OBJECTIVE: We evaluated whether a BC screening protocol in a high-risk and unique patient population had an impact on the stage of tumor presentation. DESIGN, SETTING, AND PARTICIPANTS: Forty-eight AAN-affected patients were enrolled in a screening program, establishing BC incidence during prospective screening cystoscopies and biopsies biannually for up to 10 yr. Two patients were lost to follow-up, and three refused screening after consenting. MEASUREMENTS: Patients were evaluated for presence of BC and tumor stage at diagnosis. RESULTS AND LIMITATIONS: BC was diagnosed in 25 patients (52%). Among 43 patients who underwent screening cystoscopies (median follow-up: 94 mo), 22 were first diagnosed with non-muscle-invasive BC but none with muscle-invasive tumors and none died of BC. Three women who declined follow-up were diagnosed and died with advanced metastatic disease. The limitations of our findings include the small sample size of this case series, the absence of a real control group, and the particular risk factor in these patients that differs from the usual risk factors, such as smoking or industrial chemicals. CONCLUSIONS: BC screening in high-risk groups may allow identification of tumors before muscle invasion. The optimal screening schedule and the relevance of the present findings in smoking-related BC remain to be defined.

Prostate cancer: a serious disease suitable for prevention.

Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life-expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5alpha-reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk-reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk-reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment.

Prostate cancer prevention: past, present, and future.

Prostate cancer is the most common male malignancy and the second or third leading cause of cancer death among men in the West. The descriptive epidemiology of prostate cancer suggests that it is a preventable disease. Prevention has the theoretical advantage of not only saving lives, but also reduce the morbidity of radical prostate cancer therapy. This article reviews the past, present, and future of prostate cancer prevention. In particular, the evidence and scientific data of a variety of prevention strategies are reviewed. Strategies reviewed include dietary fat reduction and supplementation with vitamins D and E, and selenium. Dietary intake of soy, green tea, and tomato-rich products (lycopene) are also reviewed. Data regarding pharmacological intervention with cyclo-oxygenease inhibitors, antiestrogens, and in particular 5-alpha reductase inhibitors are reviewed. The results of the Prostate Cancer Prevention Trial including the controversy surrounding higher-grade cancers among men randomized to finasteride are also summarized. Finally, a variety of trial designs as well as a roster of current phase 2 trials are presented. Probably no cancer is being investigated more thoroughly in the context of prevention as prostate cancer in 2007. Definitive answers to pivotal phase 3 trials will be available in the coming 2 to 7 years.

How do I treat and follow my TUNA patients.

Transurethral needle ablation (TUNA) of the prostate is an alternative treatment for benign prostatic hyperplasia (BPH) generating temperatures around 100 degrees C leading to necrotic lesions inside the prostate. TUNA is a minimally invasive, low morbidity associated, approach that uses radiofrequency energy. The needles are covered by teflon shields that protect the urethra from thermal injury. Since the introduction of TUNA, there has been a constant upgrading of the device to improve treatment quality. The main advantage of this therapy is the possibility of an outpatient care due to its anaesthesia-free option with a prostatic block. Catheterisation after the procedure is required in 10-40% of cases. Long-term data (5 years) on TUNA demonstrate a sustained improvement of both IPSS score and urinary flow. About a quarter of patients require further intervention at 5 years' follow-up. The safety profile, along with the significant improvement in both objective and subjective parameters observed after TUNA, makes it an attractive approach for symptomatic BPH.

Evaluation of male sexual function in patients with Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon), Tamsulosin or Finasteride.

OBJECTIVES: Sexual function is one of the aspects in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) that has gained increasing attention. We compared the influence on men's sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with Tamsulosin and Finasteride using a specific validated questionnaire exploring patient's sexual functions. METHODS: A database was created comprising patients from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients. Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates and prostate volume were recorded. The MSF-4 questionnaire, including 4 items that explore the patient's interest in sex, quality of erection, achievement of orgasm and ejaculation, was used across the studies. This questionnaire was demonstrated as highly reproducible and both psychometrically and clinically valid across different cultures. Correlation coefficients were given to assess the linear relationship between continuous variables. RESULTS: At 3 months, there were no statistically significant differences between the three treatment groups in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as compared to pretreatment data, there was a slight increase in sexual disorders in Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly improved with Permixon therapy (-0.2). Ejaculation disorders were the most frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on the specific MSF-4 question 4). There was no correlation between the evolution of the MSF-4 scores and the evolution in I-PSS neither in patients treated with Permixon, Finasteride or Tamsulosin. However, there was a slight correlation between the MSF-4 score at baseline and the I-PSS at baseline (r2 = 0.032). Although there was a correlation between the MSF-4 and age at baseline (r2 = 0.1452), there was no correlation between the evolution in MSF-4 during therapy and the age of the patients. CONCLUSION: The present study demonstrates that Permixon therapy has no negative impact on male sexual function. Both Finasteride and Tamsulosin had a slight impact on sexual function, especially on ejaculation, although these effects were rare and in line with previous reports about these two drugs.

Prevention of prostate cancer.

Prostate cancer is an ideal candidate for chemoprevention because of its high prevalence, long latency time, hormone dependency, precursor lesions, and its unique serum marker, PSA. Chemoprevention is the administration of drugs or other agents which aim to prevent the induction or inhibit/delay cancer progression. Large-scale studies favor environmental rather than genetic factors as key determinants of prostate cancer development. Among these environmental factors, nutrition certainly has a leading role. Numerous basic science studies but also clinical studies indicate that dietary compounds or diet modifications may ultimately play a major role in prostate cancer promotion and inhibition. Definitive proofs are often difficult because of methodological problems and complex triggering cascades. New pharmaceutical drugs with minimal toxicity are also currently evaluated.

Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers.

OBJECTIVE: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. METHODS: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. RESULTS: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s (p<0.01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p<0.001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. CONCLUSIONS: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run.

Minimally invasive therapies for benign prostatic hyperplasia in the new millennium: long-term data.

Over the last decade, a number of minimally invasive therapies have been investigated for the treatment of symptomatic benign prostatic hyperplasia. Most of these therapies use thermal energy to ablate prostatic tissue. The major common problem with all these new minimally invasive therapies has been the lack of long-term data concerning efficacy, re-intervention rates and side-effects. We present here the available long-term data on these alternative minimally invasive therapies for benign prostatic hyperplasia and their current place in the urologist's armamentarium.