Assessment of Tolerability, Response and Complications of Concurrent Chemoradiation With Capecitabine and Cisplatin in Muscle-Invasive Bladder Cancer; A Single Arm Study.

PURPOSE: To evaluate the feasibility, tolerance and efficacy of cisplatin+capecitabine as a proposed combination in concurrent chemoradiotherapy for patients with muscle-invasive bladder cancer (MIBC). METHODS: MIBC patients with stage T2-T4aN0M0 participated in this single-arm clinical trial. After maximal TURBT, 66Gy/33 daily fractions of radiation were administered with concurrent chemotherapy of cisplatin (35 mg/m2) and capecitabine (625 mg/m2). The primary endpoint was treatment tolerability, defined as receiving capecitabine+cisplatin combination for at least 5 weeks during radiation therapy. The secondary endpoints included complete response (CR) and acute toxicity rates. RESULTS: This study included 19 MIBC patients from 2018 to 2019. Eighteen patients (94.7%, 95%CI: 75.4-99.0) completed the planned treatment course. Only one patient (5.26%, 95%CI: 0.9-24.6) discontinued the treatment due to grade-3 GI toxicity. Among those who completed the treatment, CR was seen in 12 patients (66.7%, 95% CI = 44.4-88.9) with no grade ≥ 3 toxicities. The most common grade-2 side effects during therapy were renal complications (57.9%), and the only grade-2 complication after therapy was urinary-related (11.1%). The median follow-up was 31 months and the median overall survival (OS) was 31 months. The 2-year OS was 78% (95% CI 58.4-97.6), Cystectomy-free survival was 61% (95% CI: 37.5-84.5), and the median OS after recurrence was 13 months. Distant metastases were the first type of recurrence in most patients with a recurrence, which occurred in 7 (36.8%) patients. Median metastasis-free survival (MFS) was 30 months, and 2-year MFS was 66% (95% CI:45-87). CONCLUSION: The promising tolerability rate seen with concurrent cisplatin+capecitabine in this study was comparable to the available literature. Thus, this combination concurrently with radiation warrants further studies in the context of chemoradiotherapy of MIBC.

Relationship Between Perineural Invasion in Prostate Needle Biopsy Specimens and Pathologic Staging After Radical Prostatectomy.

BACKGROUND: Prostate cancer is the second most common malignancy among men worldwide and the sixth cause of cancer-related death. Some authors have reported a relationship between perineural invasion (PNI), Gleason score, and the invasion of peripheral organs during prostatectomy. However, it is not yet clear whether pathological evidence of PNI is necessary for risk stratification in selecting treatment type. OBJECTIVES: The clinical and pathological stages of prostate cancer are compared in patients under radical prostatectomy and in patients without perineural invasion. PATIENTS AND METHODS: This cross-sectional study was conducted using a sample of 109 patients who attended a tertiary health care center from 2008 to 2013. The selection criteria were PNI in prostate biopsy with Gleason scores less than six, seven, and eight to ten. The participants were enrolled in a census manner, and they underwent clinical staging. After radical prostatectomy, the rates of pathological staging were compared. The under-staging and over-staging rates among those with and without perineural invasion in biopsy samples were compared. RESULTS: The concordance between Gleason scores according to biopsy and pathology was 36.7% (40 subjects). The concordance rate was 46.4% and 33.3% among those with and without PNI, respectively. The concordance rates were significantly varied in different subclasses of Gleason scores in patients without PNI (P = 0.003); the highest concordance rate was a Gleason score of 7 (63.6%) and the lowest was a Gleason score of eight to ten (25%). However, there were no significant differences in patients with PNI (P > 0.05). CONCLUSIONS: Although the presence of PNI in prostate biopsy is accompanied by higher surgical stages, PNI is not an appropriate independent factor in risk stratification.

Concurrent Down-Regulation of PTEN and NKX3.1 Expression in Iranian Patients with Prostate Cancer.

NKX3.1 and PTEN genes are involved in the development and progression of prostate cancer (PCa). Here, in line with other studies that correlated the expression of these two genes, we aimed at evaluating the expression pattern of these genes in clinical PCa samples. Collectively, 81 tissue samples including 45 human PCa and 36 benign prostatic hyperplasia (BPH) specimens were included in the study. The tissue samples were subjected to RNA extraction and subsequently to cDNA synthesis according to the kit manufacturer's protocol. Quantitative Real-Time PCR assay was performed for each sample in triplicate reactions. REST and SPSS software were used to statistically analyze PTEN and NKX3.1 gene expression data. Expression level of both NKX3.1 and PTEN genes was down-regulated in PCa samples compared to BPH samples. The relative expression ratio of PTEN and NKX3.1 was decreased to 0.155 and 0.003, respectively (P=0.000). The results of Chi-Square analysis revealed a significant correlation between the expression of these genes in both BPH and cancer groups (P=0.004 and 0.001, respectively). According to previous studies and our data, we concluded that the association between the down-regulation of PTEN and NKX3.1 genes contributed to the prostate tumorigenesis. This might highlight the interaction between the proteins encoded by these genes. Furthermore, this finding might be exploited for the development of innovative diagnostic and therapeutic approaches in PCa.

Concurrent Down-Regulation of PTEN and NKX3.1 Expression in Iranian Patients with Prostate Cancer

ABSTRACT NKX3.1 and PTEN genes are involved in the development and progression of prostate cancer (PCa). Here, in line with other studies that correlated the expression of these two genes, we aimed at evaluating the expression pattern of these genes in clinical PCa samples. Collectively, 81 tissue samples including 45 human PCa and 36 benign prostatic hyperplasia (BPH) specimens were included in the study. The tissue samples were subjected to RNA extraction and subsequently to cDNA synthesis according to the kit manufacturer's protocol. Quantitative Real-Time PCR assay was performed for each sample in triplicate reactions. REST and SPSS software were used to statistically analyze PTEN and NKX3.1 gene expression data. Expression level of both NKX3.1 and PTEN genes was down-regulated in PCa samples compared to BPH samples. The relative expression ratio of PTEN and NKX3.1 was decreased to 0.155 and 0.003, respectively (P=0.000). The results of Chi-Square analysis revealed a significant correlation between the expression of these genes in both BPH and cancer groups (P=0.004 and 0.001, respectively). According to previous studies and our data, we concluded that the association between the down-regulation of PTEN and NKX3.1 genes contributed to the prostate tumorigenesis. This might highlight the interaction between the proteins encoded by these genes. Furthermore, this finding might be exploited for the development of innovative diagnostic and therapeutic approaches in PCa.

Transition zone prostate specific antigen density improves prostate cancer detection in Iranian men.

BACKGROUND: Prostate specific antigen (PSA) as a tumor marker has extensively changed the diagnosis of prostate cancer (PCa). With the advent of PSA, the majority of patients are diagnosed with nonpalpable early stage PCa. However, PSA lacks specificity and many patients undergo unnecessary biopsies due to an elevated serum PSA level. OBJECTIVES: This study aimed to assess the sensitivity and specificity of transition zone PSA density (TZPSAD) in detection of PCa. PATIENTS AND METHODS: This study was performed on 1712 men underwent trans-rectal ultrasound guided prostate biopsy in our institution between March 2008 and March 2013. A total of 1120 men with PSA < 20 ng/mL and normal digital rectal exam were selected for evaluation. Transition zone PSA density was calculated in all patients and the receiver operating characteristic (ROC) curve was used to analyze the accuracy of TZPSAD for the diagnosis of PCa. RESULTS: Among 1120 men who were eligible for enrolment, prostate cancer was detected in 265 patients. Mean serum PSA levels were 9.7 ± 4.3 ng/mL and 8.5 ± 3.7 ng/mL in patients with and without PCa, respectively (P < 0.001). Mean value for TZPSAD was 1.18 ± 1.19 ng/mL/mL in patients with PCa, whereas it was 0.55 ± 0.84 ng/mL in men without cancer (P < 0.001). Optimal cut-off value for TZPSAD was 0.32 ng/mL. At this cut-off value, the sensitivity and specificity values for TZPSAD were 85% and 45%, respectively. Applying the TZPSAD for PCa screening decreased 50% of unnecessary biopsies. CONCLUSIONS: Using TZPSAD as an adjunct to PSA may improve the specificity of PSA in the diagnosis of PCa and decrease the number of unnecessary prostatic biopsies in Iranian men with serum PSA level < 20 ng/mL.

Serum inhibin B concentration as a prognostic factor for prediction of sperm retrieval in testis biopsy of patients with azoospermia.

BACKGROUND: This study was conducted to determine if serum inhibin B concentration can predict spermatogenesis in azoospermic infertile men. METHODS: This cross-sectional study included 70 patients with male-factor infertility referred to Alvand and Vali-e-Asr Infertility Centers, Tehran, Iran. All patients had azoospermia. Standard evaluation consisted of history and physical examination with extreme attention to sexual history and testis examination including testis size, consistency, and presence of varicocele. Laboratory evaluation done for all cases consisted of FSH, testosterone, LH, prolactin, and inhibin B. Testis biopsy was performed in all cases with acceptable testis volume and FSH. The mean inhibin B level was compared in groups with positive and negative sperm retrieval. RESULTS: The mean+/-SEM age of 70 azoospermic patients was 32.1+/-6.2 (range: 20 - 50) years. All couples had primary infertility with a mean+/-SEM duration of infertility of 74.3+/-7.7 months. The mean+/-SEM testicular volume was 10.14+/-0.75 mL. The mean+/-SEM FSH and LH levels were 17.55+/-1.68, and 11.33+/-0.99 mIU/mL, respectively. The mean+/-SEM serum prolactin and testosterone levels were 308.77+/-17.35 and 5.45+/-0.91 ng/dL, respectively. The mean+/-SEM serum inhibin B concentration was 138.23+/-28.58 (range: 15 - 1500) pg/mL. Sperm was not retrieved in 82% of the patients; in 13% of the cases, biopsy revealed spermatogenesis. The mean+/-SEM serum FSH level of positive and negative groups was 9.78+/-2.13 and 22.56+/-2.46 mIU/mL, respectively (P<0.05). The mean serum LH, prolactin, and testosterone levels were not statistically different between the two groups. The mean+/-SEM serum inhibin B was 129+/-45.46, and 158.93+/-47.24 pg/mL in positive and negative groups, respectively (P>0.05). CONCLUSION: Inhibin B concentration is not an appropriate predicting factor for testicular spermatogenesis.

Prediction of successful sperm retrieval in patients with nonobstructive azoospermia.

INTRODUCTION: Our aim was to evaluate the predictive values of factors that indicate successful sperm retrieval in men with nonobstructive azoospermia. MATERIALS AND METHODS: We evaluated 85 infertile men with nonobstructive azoospermia who underwent multiple bilateral testicular biopsies. Factors including age, infertility period, surgical history, testicular volume, testicular consistency, serum follicle-stimulating hormone (FSH), serum inhibin B, serum luteinizing hormone, and serum total testosterone were assessed in relation to sperm retrieval results. RESULTS: Spermatozoa were retrieved in 18 biopsies (21.2%). Follicle-stimulating hormone, serum inhibin B, and testicular volume were associated with the results of sperm retrieval. Men with a higher testicular volume, a higher serum inhibin B, and a lower FSH had successful sperm retrieval. The cutoff points were determined as 9.5 mL for testicular volume, 9.9 IU/L for serum FSH, and 39.8 pg/mL for serum inhibin B. These 3 factors had strong correlations with each other. The sensitivities and specificities were 88.9% and 94% for testicular volume, 97% and 83.3% for FSH, and 72.2% and 95.5% for serum inhibin B, respectively. The positive predictive value for a combination of serum FSH and inhibin B was 100%. CONCLUSION: Serum FSH and serum inhibin B are useful markers for evaluation of the presence of sperm in patients with nonobstructive azoospermia. Inhibin B has a high specificity when combined with serum FSH and their measurements can be helpful in all patients with nonobstructive azoospermia before decision making for sperm retrieval.