Prostate Cancer Treatment-Related Toxicity: Comparison between 3D-Conformal Radiation Therapy (3D-CRT) and Volumetric Modulated Arc Therapy (VMAT) Techniques.

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan−Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance.

Stereotactic Radiotherapy and Androgen Deprivation Therapy for Localized Prostate Cancer: A Retrospective Mono-institutional Experience.

BACKGROUND/AIM: Stereotactic radiotherapy (SRT) is an effective treatment for localized prostate cancer. However, is it not clear whether the addition of androgen deprivation therapy (ADT) to SRT is beneficial. The aim of this study was to analyze the outcomes of a series of patients treated with SRT plus ADT for localized prostate cancer. PATIENTS AND METHODS: Patients were treated with SRT with 42 Gy in 7 fractions with volumetric-modulated arc therapy plus Image Guided Radiotherapy (V-MAT IGRT) technique. ADT was administered to patients with intermediate unfavorable- and high-risk disease. Study endpoints were biochemical disease-free survival (bDFS), overall survival (OS), acute and late toxicity and patient-reported outcomes (PROs) using international prostate cancer symptoms scale (IPSS) and international index of erectile function (IIEF). RESULTS: A total of 170 consecutive patients were identified, of which 49 (28.8%) with low-risk, 15 (8.8%) with favorable intermediate-risk 76 (44.7%) with unfavorable intermediate-risk and 30 (17.6%) with high-risk class. All patients of unfavorable intermediate- and high-risk groups were administered LHRH analogue concurrently to SRT and for at least 6 months. Patients with unfavorable intermediate- and high-risk presented a 5-year bDFS of 81.7% and 76.9%, respectively. CONCLUSION: SRT consisting of 42 Gy in seven fractions with short-term ADT represents a safe and effective treatment for unfavorable intermediate and high risk prostate cancer. Our results support the need of high quality studies to test the efficacy of ADT combined with SRT for unfavorable intermediate- and high-risk localized prostate cancer.

Metabolic syndrome and stone disease.

Metabolic syndrome (MetS) is a clustering of several pathological medical conditions including hypertension, impaired glucose tolerance/diabetes, abdominal obesity and dyslipidemia. In the last two decades, MetS has reached an epidemic stage, with an estimated prevalence in the range of 30% among the American adult population and a constant increase for all age categories. The incidence of nephrolithiasis between different geographical areas, ranging 1% to 13%; however, a worldwide increase has been recently reported. There is consistent evidence in the literature both about the association between metabolic syndrome/metabolic syndrome traits and kidney stones. Conversely, less is known about the underlying mechanisms and the complex interplay between metabolic syndrome traits. In this work, we sought to review the literature and to summarize the available evidence regarding the association between metabolic syndrome and nephrolithiasis, the biological mechanisms linking metabolic syndrome and its trait to stone formation, and stone composition in individuals affected by metabolic syndrome. In conclusion, we would like to stress the concept of "appropriate" dietary habits and lifestyle as a key concept in the prevention of both metabolic syndrome and nephrolithiasis.

Hypofractionated simultaneous integrated boost (IMRT-SIB) with pelvic nodal irradiation and concurrent androgen deprivation therapy for high-risk prostate cancer: results of a prospective phase II trial.

OBJECTIVE: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. MATERIALS AND METHODS: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012. All patients enrolled (41) received in 25 fractions a total dose of 67.5 Gy (2.7 Gy/fraction) to the prostatic volume, 56.25 Gy (2.25 Gy/fraction) to the seminal vescicles, and 50 Gy (2.0 Gy/fraction) to the pelvic lymph nodes (LN) chains with concurrent androgen deprivation therapy (ADT). The image-guided radiotherapy (IGRT) procedure was performed using three gold seeds. RTOG late gastrointestinal and genitourinary toxicities and 6-year biochemical relapse-free survival (BRFS) were assessed in combination of their statistical correlation with clinical factors and dosimetric parameters. RESULTS: Rate of late genitourinary toxicity grade 2 was 9.8%, while rates of late gastrointestinal toxicity were 14.6% and 2.4%, for grade 1 and 2, respectively. Diabetes and maximum doses to rectum appeared to be statistically relevant risk factors for late rectal toxicity. Five-year BRFS was 95.1%. CONCLUSIONS: In our study, we observed positive results in terms of toxicity and good efficacy in a cohort of high-risk prostate cancer patients treated with a multimodality therapy approach comprising hypofractionation, irradiation of pelvic nodes (common iliac nodes included), and concurrent ADT. These favorable results may merit further investigation in a phase III randomized trial to confirm that whole pelvic radiation therapy (WPRT) combined with moderate hypofractionation and ADT could be performed safely and effectively.

Melanoma in situ of penis: a very rare entity: A case report and review of the literature.

RATIONALE: Melanoma in situ of the penis is very rare and there are no clear guidelines for its surgical treatment. PATIENT CONCERNS: The authors describe the case of a 69-year-old man who presented with an asymptomatic brown macula on his glans penis and foreskin that appeared about 8 years earlier, enlarged in the last few months. DIAGNOSES: A diagnostic biopsy showed the characteristics of a melanoma in situ. INTERVENTIONS: The authors decided to excise the lesion keeping a healthy margin of 1 cm all over around except close to the urethral meatus, where it was impossible, and where only 5 mm of free margin was excised. A full thickness mucosal graft from oral cavity was performed to repair the defect. OUTCOMES: No recurrence or metastasis occurred during 50 months after the operation. LESSONS: Considering that at the sixth clinical follow-up the patient was alive and disease free at 50 months after surgery, the chosen treatment has proved successful.

Efficacy and safety of combined oral therapy with tadalafil and alfuzosin: an integrated approach to the management of patients with lower urinary tract symptoms and erectile dysfunction. Preliminary report.

INTRODUCTION: Alpha1-blockers (AB) are the first-line monotherapy for lower urinary tract symptoms (LUTS). Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction (ED). Numerous studies have supposed a significant association between ED and LUTS, but a causal relationship cannot be established. AIM: The aim was to evaluate the efficacy of a combined therapy with an AB (alfuzosin) and PDE5 inhibitors (tadalafil) in patients with LUTS and ED. METHODS: This was a randomized, open-label, three-arm study. A total of 66 men complaining of ED and LUTS were included in the study. Patients were assessed at baseline and after 12 weeks of study treatment, and then underwent randomized allocation to either alfuzosin 10 mg once a day (22 patients) or tadalafil 20 mg on alternative days (21 patients), or a combination of both (23 patients). MAIN OUTCOME MEASURES: All participants completed the erectile function domain of the International Index of Erectile Function (IIEF-EF) and the International Prostatic Symptom Score (IPSS). Other efficacy variables included maximum urinary flow rate (Qmax) and medium urinary flow rate (Qave). RESULTS: IIEF-EF tended to improve with alfuzosin alone (+15%), while it was clearly improved with tadalafil alone (+36.3%). The greatest improvement was experienced with the combination therapy (+37.6%). Improvement in Qmax was observed in all groups, but patients receiving combination therapy had greater improvement (29.6%) than patients receiving either only alfuzosin (21.7%) or only tadalafil (9.5%). IPSS was significantly improved in alfuzosin group (27.2%), was more marked with the combination therapy (41.6%), and a small increase, although not significant, was also observed with tadalafil (8.4%). CONCLUSIONS: Combined therapy improved ED and LUTS as demonstrated by the significant improvement in uroflowmetry measures and in IPSS and IIEF-EF scores. A significant improvement was also observed in quality of life assessments. The beneficial effects of tadalafil on LUTS similar to the benefits of alfuzosin on ED, although present, were smaller.

How accurately do Solsona and European Association of Urology risk groups predict for risk of lymph node metastases in patients with squamous cell carcinoma of the penis?

OBJECTIVES: To compare the prognostic accuracy of the Solsona and European Association of Urology (EAU) risk groups in the identification of lymph node involvement in a cohort of patients with squamous cell carcinoma of the penis. METHODS: The clinical and pathologic data of 175 patients who had undergone surgery for squamous cell carcinoma of the penis from 1980 to 2002 at 11 urologic centers of northeastern Italy were retrospectively collected. RESULTS: According to the EAU risk group, 25 patients were categorized as at low (15.1%), 23 (13.9%) as intermediate, and 118 (71.1%) as high risk of lymph node metastasis. Similarly, using the criteria of the Solsona risk group stratification, 25 (15.1%), 55 (33.1%), and 86 patients (51.8%) were categorized as at low, intermediate, and high risk. At the median follow-up of 26 months, lymph node involvement was observed in 71 (40.6%) of 175 patients. Receiver operating characteristic curve analysis showed that both the EAU risk group (area under the curve = 0.632) and Solsona risk group (area under the curve = 0.697) had a low accuracy for predicting lymph node involvement. Both risk groups were independent predictors of lymph node involvement, as well as the clinical stage of lymph node involvement and the presence of vascular and/or lymphatic embolization. CONCLUSIONS: The Solsona and EAU risk groups were both independent predictors of lymph node involvement, although the receiver operating characteristic curve analysis showed that both risk groups had low predictive accuracy.

Lipoid-cell variant of urothelial carcinoma: report of a new case of the urinary bladder.

We report a new case of urothelial lipoid carcinoma of the urinary bladder, occurring in a 71 year-old woman. The tumor presented with metastatic involvement of the left axillary and supraclavicular lymph nodes. Clinical work up revealed a large infiltrating bladder tumor microscopically featuring poorly differentiated, pleomorphic cells with nuclear pleomorphism and frequent mitoses. Large, optically clear intracytoplasmic vacuoles imparting an adipocytic or signet-ring cell appearance could be noticed. Areas of conventional urothelial carcinoma were present as well. Due to the extensive invasion of the bladder coat, distant metastases as well as poor performance status radical cystectomy was not performed. The patient was treated with multimodality conservative therapy and is alive 9 months after the diagnosis.

Role of transperineal six-core prostate biopsy in patients with prostate-specific antigen level greater than 10 ng/mL and abnormal digital rectal examination findings.

OBJECTIVES: To define whether six-core biopsies still have a role in patients presenting with prostate-specific antigen (PSA) levels greater than 10 ng/mL and abnormal digital rectal examination (DRE) findings. Recent studies have suggested that the six-core biopsy is inadequate for the diagnosis of prostate cancer; however, it remains controversial whether an increased number of cores is justified in all patients. METHODS: From June 2002 to February 2005, 122 (18.8%) of 650 patients underwent prostate biopsy because of a PSA level greater than 10 ng/mL and abnormal DRE findings. All patients underwent transperineal ultrasound-guided prostate biopsy in a standardized fashion: a six-core biopsy was performed first, followed by six additional cores during the same session, four in the peripheral and two in the transition zone. RESULTS: The detection rate in patients with a PSA level greater than 10 ng/mL and abnormal DRE findings was 72.1% (88 of 122) and 75.4% (92 of 122) using the 6-core and 12-core biopsy, respectively. One case of tumor was missed by the six-core biopsy among patients with a PSA level greater than 15 ng/mL and abnormal DRE findings. No cases of tumor were missed by six-core biopsy in the group with a PSA level greater than 20 ng/mL and abnormal DRE findings. CONCLUSIONS: Six-core biopsy provided a similar cancer detection rate compared with 12-core biopsy in patients with PSA levels greater than 10 ng/mL and abnormal DRE findings. An initial approach with 6-core biopsy is reasonable in patients with a PSA level greater than 10 ng/mL and abnormal DRE findings and is advocated in those with PSA greater than 20 ng/mL and abnormal DRE findings.

Role of risk factors for erectile dysfunction in patients undergoing transurethral resection of the prostate: early impact on sexual function.

INTRODUCTION: Transurethral resection of the prostate (TURP) has been long debated as a possible cause of erectile dysfunction (ED). We investigated the role of common risk factors for ED in patients aged 60 to 70 undergoing TURP Factors related to the treatment were also considered. MATERIALS AND METHODS: Ninety patients underwent TURP for benign prostate hyperplasia (BPH) from June 2002 to February 2003. Fourty-two of them, sexually active aged 60 to 70, were administered preoperatively and 3-month postoperatively the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. A complete assessment of risk factors for ED was performed in the preoperative setting (treated hypertension, diabetes, cigarette smoking, hypercolesterolemy, cardiovascular disease). IIEF score was related to age, comorbidities, operative time, resected tissue weight, retrograde ejaculation, IPSS score. RESULTS: Nine (21.4%) patients reported worsened IIEF-5 score after TURP, and 33 (78.6%) unchanged/improved score. Cardiovascular disease was present in 56% of patients with worsened IIEF-5 score and in 12% of patients with improved/unchanged IIEF-5 score; it was the only factor that correlated significantly in the regression model. CONCLUSION: In general, most patients report a stable sexual function after TURP. Patients with known cardiovascular disease undergoing TURP had an increased risk of sexual impairment after this procedure.

Early surgical repair of penile fractures: our experience.

OBJECTIVE: Fracture of the penis is a relatively rare condition, defined as the rupture of the tumescent corpora cavernosa. The fracture is quite easily recognized, whereas its management remains controversial. Our experience regarding the early treatment of penile fractures is herein reported. MATERIALS AND METHODS: In a 7-year period (1997-2004) 10 patients aged 23 to 42 years, presented with a penile fracture, occurred during coitus. All patients were admitted to the hospital 1 to 10 hours after injury. Diagnosis was made on clinical examination. Six patients referred a snapping sound at the time of injury. Common clinical features included sudden penile pain, detumescence and penile deviation. All patients showed penile haematoma; 3 had scrotal and perineal haematoma as well. None of the patients had urethral bleeding. RESULTS: all patients were surgically treated; at the time of surgery unilateral albuginea rupture was found in all cases. With a mean follow-up of 37 months (range 1-78) all cases were able to achieve an adequate erection. No complications, such as deformations, penile plaque, urethral fistula or erectile dysfunction were reported. CONCLUSION: Immediate surgical repair in case of penile fracture is recommended in order to obtain better functional outcome and to avoid potential complications.