Francesco Soria

A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?

Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double‐blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP).

Validation of Preoperative Risk Grouping of the Selection of Patients Most Likely to Benefit From Neoadjuvant Chemotherapy Before Radical Cystectomy

Micro‐Abstract Neoadjuvant chemotherapy (NAC) has been demonstrated to be effective in prospective randomized trials for cT2‐cT4a N0 patients. However, this benefit was more evident in patients with clinical stage ≥ T3 disease. On the other hand, toxicity grade 3 and 4 were reported in 35% and 37% of patients who underwent NAC. Following these considerations, we validate here the preoperative risk model proposed by Culp et al as a fundamental tool in the preoperative prediction of patients who will benefit more from NAC administration. Introduction: The aim of this study was to validate the value of preoperative patient characteristics in prognosticating survival after radical cystectomy (RC) to guide treatment decisions regarding neoadjuvant systemic treatment. Methods: We evaluated a single cohort of 449 consecutive patients treated with RC for bladder cancer. Patients treated with neoadjuvant therapy were excluded from the study cohort (n = 24). Patients were stratified based on preoperative characteristics into 2 risk groups. The high‐risk group included patients harboring clinically non–organ‐confined disease (≥ cT3), hydroureteronephrosis, lymphovascular invasion, or variant histology (micropapillary, neuroendocrine, sarcomatoid, or plasmacytoid variants on transurethral resection). The low‐risk group included patients with cT2 disease without any of the aforementioned features. Survival expectancies after surgery were evaluated using competing risk and Kaplan‐Meier analyses. Results: We identified 153 (44.6%) low‐risk and 190 (55.4%) high‐risk patients. The majority of high‐risk patients had only 1 high‐risk feature (n = 111; 58.4%); the most common high‐risk feature was preoperative hydroureteronephrosis (n = 107; 56.3%). The majority of low‐risk patients were upstaged at time of RC (n = 118; 70.6%), whereas a pathologic downstage occurred only in 27 high‐risk patients (14.2%). Cancer‐specific mortality‐free rates at 5 years after RC were 77.4% versus 64.4% for low‐risk versus high‐risk patients, respectively. Conclusions: We confirm that preoperative risk features can stratify patients with muscle‐invasive bladder cancer into differential risk groups regarding survival. Decision‐making regarding neoadjuvant systemic therapy administration is likely to be improved by integrating clinical stage, lymphovascular invasion, variant histology, and hydroureteronephrosis.

Characteristics and clinical significance of histological variants of bladder cancer.

In the past 10 years evidence for the clinical relevance of variant histology in urinary bladder cancer has been increasing. This increase has resulted in new classifications of urothelial cancers by the WHO in 2016, highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. The rising awareness of the importance of an accurate pathological report manifests itself in the increasing prevalence of reporting of variant histology in daily practice. Histological variants can generally be divided into urothelial and nonurothelial. Urothelial variants often have similar features that also have specific morphological phenotypes, whereas nonurothelial variants have independent features. Overall, histological variants follow a more aggressive clinical course than conventional urothelial carcinoma, but conclusive data on their effect on survival are currently lacking. The clinical relevance of variant histology can manifest at three different levels: diagnostic, as identification is challenging and misinterpretation is not uncommon; prognostic, for patient risk stratification and outcome estimation; and therapeutic, as particular variants could be responsive to specific treatment strategies. An accurate morphological description of histological variants is necessary for patient consultation and therapy planning. Moreover, the association of variant histology with specific mutation patterns promises to be helpful in discovering targeted therapeutic approaches based on specific molecular pathways.

Two cases of retroperitoneal metastasis from a completely regressed burned-out testicular cancer.

Introduction Primary extragonadal germ cell tumors (EGCT) are rare and it is still a matter of debate if they have to be considered as primary extragonadal issues or metastases from a primary testicular neoplasm. We describe two cases of the so-called burned-out seminoma, a primary testicular germ-cell tumor that spontaneously regressed after demonstration of retroperitoneal metastases. Cases Presentation Two patients (35 and 50 years old, respectively) presented with CT findings of retroperitoneal masses. In both cases physical examination of the testis was not suspicious, and only scrotal ultrasound (SUS) showed parenchymal alterations such as scarring, calcifications and nodular lesions. Left orchiectomy and chemotherapy were then performed in both cases. Currently, they are both free of disease. Conclusions Although primary germ cell tumors may be of retroperitoneal origin, the likelihood of metastasis from a testicular primary origin should always be carefully considered in order to avoid misdiagnosis and to apply the best treatment schedule for the patients. Therefore, a testicular ultrasonography is mandatory in patients presenting CT findings of retroperitoneal adenopathy, even if patients are completely asymptomatic and their physical examination appears normal.

Incidence and effect of variant histology on oncological outcomes in patients with bladder cancer treated with radical cystectomy

INTRODUCTION We sought to describe incidence of histological variants after radical cystectomy (RC) due to bladder cancer (BCa). Moreover, we investigated survival outcomes accounting for this parameter. METHODS We retrospectively evaluated data from 1,067 patients with BCa treated with RC between 1990 and 2013 at a single tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the effect of different histopathological variant on recurrence, cancer-specific mortality (CSM), and overall mortality (OM) after accounting for all available confounders. RESULTS Of 1,067 patients, 729 (68.3%) harbored pure urothelial BCa while 338 (31.7%) were found to have a variant. Considering uncommon variants, 21 (2.0%) were sarcomatoid, 10 (0.9%) lymphoepitelial, 19 (1.8%) small cell, 109 (10.2%) squamous, 89 (8.3%) micropapillary, 23 (2.2%) glandular, 34 (3.2%) mixed variants, and 33 (3.1%) were found with other types of variants. With a median follow-up of 6.2 years, 343 recurrence, 365 CSM, and 451 OM were recorded, respectively. At multivariable Cox regression analyses, the presence of small cell variant was associated with higher recurrence (hazard ratio [HR] = 3.47, P<0.001), CSM (HR = 3.30, P<0.04), and OM (HR = 2.97, P<0.003) as compared with pure urothelial cancer. Conversely, no survival differences were recorded considering other histological variants (all P> 0.1). CONCLUSION Our study confirms that histological variant is not an infrequent event at RC specimen. However, in our single-center series, only patients found with small cell variant were associated with a negative effect on survival after RC.

Adrenal Ganglioneuroma with Multifocal Retroperitoneal Extension: A Challenging Diagnosis

A ganglioneuroma (GN) is the rarest and most benign of the neuroblastic tumors and originates from neural crest cells wherever sympathetic nervous tissue exists, such as in the retroperitoneum and adrenal gland. The diagnosis can be very challenging, given the rarity and asymptomatic presentation of this neoplasia, and can be achieved only by means of histological evaluation. Although benign, a few cases of metastatic GNs have been reported in the literature. The prognosis, however, seems to be excellent after surgical resection. We describe a rare case of multifocal retroperitoneal GN, diagnosed incidentally in a 46-year-old woman, with para-aortic and adrenal localizations. After intraoperative pathological diagnosis was made, complete excision of all the visible masses was performed. The postoperative period was uneventful and she was recurrence free 3 months after surgery. To our knowledge, this is the first case report of a multifocal retroperitoneal GN. Among the broad differential diagnoses of adrenal incidentalomas, an adrenal location of neuroblastic tumors should not be forgotten.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Primary Non–muscle-invasive Bladder Cancer

Micro‐Abstract The neutrophil‐to‐lymphocyte ratio is associated with poor outcomes in patients with muscle‐invasive bladder cancer. We found that the neutrophil‐to‐lymphocyte ratio is independently associated with disease recurrence and progression in patients with non–muscle‐invasive bladder cancer. Introduction: The purpose of this study was to assess the role of pretreatment neutrophil‐to‐lymphocyte ratio (NLR) as a predictor of clinical outcomes in patients treated with transurethral resection (TURB) for primary non–muscle‐invasive bladder cancer (NMIBC). Patients and Methods: Data from 918 patients treated with TURB for primary NMIBC were retrospectively collected. NLR was evaluated as binary variable with the cut‐point of 3 based on the visual best correlation of the receiver operating curve analyses focusing on disease recurrence. The median follow‐up was 62 months. Cox regression analyses were used to evaluate associations with recurrence (RFS) and progression‐free survival (PFS). Subgroup analyses were done according to risk groups and receipt of intravesical bacillus Calmette‐Guérin therapy. Results: Overall, 293 patients had a NLR ≥ 3. High NLR was associated with pathologic T stage and smoking status. The 5‐year RFS and PFS for NLR < 3 and NLR ≥ 3 were, respectively, 55.5% versus 45.9% (P = .01) and 94.9% versus 89.9% (P = .004). On multivariable analyses, NLR ≥ 3 remained significantly associated with RFS and PFS. The addition of NLR increased the discrimination of a multivariable model by 0.6% and 2.3% for RFS and PFS, respectively. Moreover, NLR showed a trend in the association with outcomes in patients treated with intravesical bacillus Calmette‐Guérin therapy. Conclusions: Integration of NLR in a prediction model could be helpful in predicting RFS and PFS in patients with primary NMIBC and identifying those who are likely to fail therapy and may benefit from an early radical cystectomy. Limitations are associated to the retrospective design.

Management of muscle invasive, locally advanced and metastatic urothelial carcinoma of the bladder: a literature review with emphasis on the role of surgery

Locally advanced (T3b, T4 and N1−N3) and metastatic urothelial bladder cancer (BCa) is a lethal disease with poor survival outcomes. Combination chemotherapy remains the treatment of choice in patients with metastatic disease and an important part of treatment in addition to radical cystectomy (RC) in patients with locally advanced tumour. Approximately half of patients who underwent RC for muscle invasive BCa relapse after surgery with either local recurrence or distant metastasis. This review focuses on the management of muscle invasive, locally advanced and metastatic BCa with emphasis on the role of surgery; to summarize the current knowledge in order to enhance clinical decision-making and counselling process.

Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio as biomarkers for predicting lymph node metastasis and survival in patients treated with radical cystectomy.

To evaluate the role of lymphocyte‐to‐monocyte ratio (LMR) and neutrophil‐to‐lymphocyte ratio (NLR) as pre‐operative markers for predicting extravesical disease and survival outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

Pseudoprogression and hyperprogression during immune checkpoint inhibitor therapy for urothelial and kidney cancer

ObjectivesA small subset of patients treated with immune checkpoint inhibitors manifest atypical patterns of response, the so-called pseudoprogression (PP) and hyperprogression (HP). Their prevalence in urothelial (UC) and renal cancer (RCC) remains, to date, mostly uninvestigated. Therefore, we aimed to provide a summary of the current knowledge about PP and HP during immune checkpoint inhibitor therapy in UC and RCC patients.Methods and materialsA systematic medline/pubmed© literature search was performed. The atypical patterns of response to systemic immunotherapy were reviewed. Endpoints were PP and HP in UC and RCC.ResultsTumors respond differently to immunotherapy compared to systemic chemotherapy. To evaluate response to immunotherapy, new guidelines (iRECIST) have been developed. To date, no studies focused on PP in UC and RCC, and the only way to evaluate its role is to take patients who respond to treatment beyond progression as surrogate for pseudoprogressors. PP seems to occur in a non-negligible rate of UC and RCC (from 1.5 to 17% and from 5 to 15%, respectively). The concept of HP, defined as a rapid progression after treatment, just took the first steps, and therefore, data from ongoing trials are awaited to elucidate its impact in genitourinary cancers.ConclusionsPP and HP are not uncommon entities in UC and RCC patients, treated with PD-1/PD-L1 inhibitors. Further investigation is warranted to define which patients are likely to experience PP and could benefit from treatment beyond progression and which ones will instead rapidly experience progression despite treatment and should, therefore, avoid systemic immunotherapy.