The management of localized prostate cancer requires a balance between oncological control and functional preservation.Focal therapy, as an emerging strategy between radical treatment and active surveillance, enables precise tumor ablation based on multiparametric magnetic resonance imaging, prostate-specific membrane antigen (PSMA) -guided imaging and targeted biopsy.Techniques including cryotherapy, high-intensity focused ultrasound, irreversible electroporation, and vascular-targeted photodynamic therapy have demonstrated favorable functional outcomes in short-to mid-term follow-up. However, their long-term efficacy and optimal indications remain to be verified.This article summarizes recent international advances in focal therapy for prostate cancer and introduces the “Penta-Managing System” developed by the multidisciplinary urology team at Fudan University Shanghai Cancer Center based on the full-process application of irreversible electroporation, providing insights for the standardized and individualized use of focal therapy.

In recent years,the combined application of targeted-immunotherapy has become a recommended treatment option for advanced renal cell carcinoma in various guidelines.However,although this strategy has significant therapeutic effects and survival advantages,it is associated with a variety of adverse reactions that cannot be ignored.Therefore,how to effectively manage adverse reactions and ensure the treatment safety has become one of the core issues.This article systematically reviews the adverse effects and management strategies,discusses the early identification of adverse reactions,monitoring methods,the design of individualized treatment plans and future development,aiming to provide practical safety management guidance and explore the direction of future development.

In recent years,the combined application of targeted-immunotherapy has become a recommended treatment option for advanced renal cell carcinoma in various guidelines.However,although this strategy has significant therapeutic effects and survival advantages,it is associated with a variety of adverse reactions that cannot be ignored.Therefore,how to effectively manage adverse reactions and ensure the treatment safety has become one of the core issues.This article systematically reviews the adverse effects and management strategies,discusses the early identification of adverse reactions,monitoring methods,the design of individualized treatment plans and future development,aiming to provide practical safety management guidance and explore the direction of future development.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Ductal adenocarcinoma(DAC)is the most common histological variant of prostate cancer with an aggressive characteristic.Due to the rarity of the disease,DAC can be difficult to identify by traditional diagnostic modalities such as serum prostate-specific antigen(PSA)and multi-parameter magnetic resonance imaging.Optimal treatment mode for local DAC is still under exploration.After radical prostatectomy or radiotherapy,most DACs are prone to recurrence or metastasis at low PSA levels,and systemic therapy for high-risk prostate cancer is less effective in the treatment of DAC.Current genomic analysis of DAC has provided laboratory evidence for its aggressive behavior and potential therapeutic targets,but the exploration of the mechanism of the biological behavior of DAC still needs to be addressed.

Objective:To explore the efficient prognostic factors of cryotherapy for prostate cancer in the real-world setting.Methods:The clinical data of 105 prostate cancer patients treated at the Fudan University Shanghai Cancer center from January 2021 to December 2023 were analyzed retrospectively. The patients were divided into a non-metastatic group (62 cases, 58.7%) and a metastatic group (43 cases, 41.3%) based on the presence or absence of distant metastasis. In the non-metastatic group, the median age was 79 years (range 73 to 82), the initial PSA was 20 ng/ml (range 10 to 47), 37 cases (59.7%) received neoadjuvant endocrine therapy, and the preoperative PSA was 8 ng/ml (range 2 to 14). The ISUP grades were Grade 1 in 4 cases (6.5%), Grade 2 in 11 cases (17.7%), Grade 3 in 16 cases (25.8%), Grade 4 in 16 cases (25.8%), and Grade 5 in 15 cases (24.2%). The T-stages were T 2 in 49 cases, T 3 in 6 cases, and T 4 in 7 cases. All cases were N 0. In the metastatic group, the median age was 68 years (range 62 to 74), the initial PSA was 64 ng/ml (range 27 to 200), 42 cases (97.7%) received neoadjuvant endocrine therapy, and the preoperative PSA was 0 ng/ml (range 0 to 3). The ISUP grades were Grade 1 in 0 cases, Grade 2 in 5 cases (11.6%), Grade 3 in 3 cases (7.0%), Grade 4 in 19 cases (44.2%), and Grade 5 in 16 cases (37.2%). The T-stages were T 2 in 29 cases (67.4%), T 3 in 8 cases (18.6%), and T 4 in 6 cases (14.0%). The N-stages were N 0 in 38 cases (88.4%) and N 1 in 5 cases (11.6%). The M-stages were M 1a in 5 cases (11.6%), M 1b in 35 cases (81.4%), and M 1c in 3 cases (7.0%). The difference in T-stage between the two groups was not statistically significant ( P=0.346), while differences in other indicators were statistically significant ( P<0.05). The cryotherapy for prostate cancer was performed under general or local anesthesia, with the patients in the lithotomy position and a F20 three-lumen catheter was placed for continuous irrigation. Under transrectal ultrasound guidance, the cryoprobes were inserted parallel to the probe through the perineum, with a safe distance of 3 mm from the bladder wall. A whole-gland freezing mode was adopted, starting from the ventral side and freezing layer by layer towards the rectal side. Ultrasound was used in real-time to observe the ice ball's position and extent, adjusting it during ablation to conform to the prostate's margins while protecting surrounding structures. After ablation, the cryoprobes were removed, the puncture sites were disinfected with povidone-iodine, and gauze was applied for 20 seconds to achieve hemostasis before applying dressings. The catheter was removed 10 days postoperatively. PSA levels were rechecked on the first postoperative day and at 6 and 12 weeks postoperatively. The ratio of PSA on the first postoperative day to preoperative PSA was defined as the PSA release rate. Biochemical recurrence was defined as a PSA increase of more than 0.2 ng/ml above the postoperative nadir. The PSA progression-free survival time and the incidence of complications were compared between the two groups. Results:All procedures were successfully completed. The PSA release rates for the non-metastatic and metastatic groups were 4.2 (2.2, 6.4) and 3.9 (1.5, 6.7), respectively, with no statistical significant difference ( P=0.8272). The median PSA at 6 weeks postoperatively was 0.23 (0.01, 1.22) ng/ml, and at 12 weeks it was 0.02 (0.01, 0.49) ng/ml. The median PSA for the non-metastatic group was 0.42 (0.25, 1.00) ng/ml at 6 weeks, and it was 0.03 (0.01, 0.57) ng/ml at 12 weeks. For the metastatic group, the median PSA was 0.30 (0.14, 0.50) ng/ml at 6 weeks, and it was 0.02 (0.01, 1.17) ng/ml at 12 weeks. The median follow-up period was 339 days (range 128 to 571). No Clavien-Dindo grade ≥2 complications occurred postoperatively. One case (0.9%) experienced bladder neck stricture one month postoperatively, which improved by transurethral resection of the prostate (TURP). Two cases (1.9%) experienced urinary retention seven days postoperatively, which resolved after re-catheterization for two weeks. No urinary incontinence was reported. Two non-tumor-related deaths occurred (1.9%), one due to cardiac disease and the other due to complications from COVID-19. During follow-up, 29 cases (27.6%) experienced PSA progression, with a median PSA progression-free survival time of 808.0 days. The median PSA progression-free survival time was not reached in the non-metastatic group, while it was 764.0 days in the metastatic group. There was no statistical significant difference in PSA progression-free survival between the two groups ( P=0.422). Univariate analysis showed that preoperative PSA ( HR=1.02, 95% CI 1.00-1.03, P=0.048), T 3 stage ( HR=9.00, 95% CI 2.59-31.25, P<0.01), and T 4 stage ( HR=5.83, 95% CI 1.68-20.21, P=0.005) were prognostic factors for PSA progression-free survival. Multivariate analysis showed that T 3 stage ( HR=9.08, 95% CI 2.47-33.45, P<0.01) and T 4 stage ( HR=4.50, 95% CI 1.18-17.22, P=0.028) were independent prognostic factors for PSA progression-free survival. Conclusions:Cryotherapy for prostate cancer has a high safety profile. The efficacy of Cryotherapy is better in patients with T-stage

Background and purpose:Both prostate-specific membrane antigen(PSMA)positron emission tomography/computed tomography(PET/CT)and circulating tumor DNA(ctDNA)sequencing outcomes serve as references for therapeutic decision-making in hormone-sensitive prostate cancer(HSPC)treatment.This study aimed to analyze the association between PSMA PET/CT-derived parameters and ctDNA characteristics in patients with HSPC.Methods:HSPC patients who received PSMA PET/CT and ctDNA sequencing at an interval of less than 2 weeks and with complete medical records were retrospectively included in Fudan University Shanghai Cancer Center.Patients with active malignancies other than prostate cancer and those with histological features supporting a diagnosis of pure neuroendocrine carcinoma or small cell carcinoma were excluded.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:1909207-12).The correlation between PSMA PET/CT-derived parameters,including the maximum standardized uptake value(SUVmax),total tumor volume(TTV),total lesion uptake(TLU)and ctDNA fraction(ctDNA%)was evaluated using the Spearman correlation coefficient.Results:A total of 60 HSPC patients were included,with TP53(3.3%),BRCA2(3.3%)and ATM(3.3%)being the most common mutated genes.In the correlation analysis,a significant correlation was observed between ctDNA%and SUVmax levels(Spearman's rho=0.272,P=0.036);however,no significant correlation was found between ctDNA%and TLU(Spearman's rho=0.160,P=0.222)or TTV(Spearman's rho=0.162,P=0.215).Conclusion:There was a significant correlation between SUVmax and ctDNA%,suggesting that patients with high PSMA uptake lesions were more likely to receive combined targeted therapy than patients with no PSMA positive lesions and patients with low PSMA uptake lesions,which provided a certain reference for the formulation of individualized treatment plans.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Objective:To investigate the clinicopathological features and prognosis of patients with penile cancer.Methods:The clinical data of 362 patients with penile cancer who underwent surgery in Fudan University Shanghai Cancer Center from January 2005 to December 2020 were retrospectively analyzed. The mean age was (57.0±0.7) years. According to the clinical N stage classification, 239 patients were in N 0 stage, 57 patients in N 1 stage, 37 patients in N 2 stage, and 29 patients in N 3 stage. All these patients had no metastasis. Based on tumor size and location, 50 patients underwent extended circumcision, 283 patients underwent partial penectomy, and 29 patients underwent total penectomy. One hundred and eighty-three patients underwent inguinal lymphadenectomy and 47 patients underwent pelvic lymphadenectomy. Tumor pathology, tumor size, HPV subtype, postoperative pathological stage, overall survival (OS) and prognosis were analyzed. The Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyse the factors which could affect the survival of patients. 5-year OS rate of these patients were also calculated. Results:In the pathological T classification, 137 cases were in T 1a stage, 24 cases in T 1b stage, 51 cases in T 2 stage, 136 cases in T 3 stage, and 14 cases in T 4 stage. In the pathological N classification, 235 cases were in N 0 stage, 54 cases in N 1 stage, 31 cases in N 2 stage and 42 cases in N 3 stage. The most common tumor type was squamous cell carcinoma (300 cases, 83%), followed by verrucous carcinoma (40 cases, 11%), sarcomatoid carcinoma(7 cases), carcinoma in situ (6 cases), basal-like carcinoma (6 cases), and adenosquamous carcinoma (3 cases). The most common tumor grade was mild (160 cases, 44%), followed by moderate differentiation (130 cases, 36%), poor differentiation (46 cases, 13%), and unclear differentiation (26 cases). The tumor sizes were < 3 cm in 135 patients and ≥ 3 cm in 142 patients. The tumor size was unclear in 85 patients. 173 cases (48%) were HPV positive and 189 cases (52%) were HPV negative. The Kaplan-Meier analysis showed the 5-year OS rate of HPV-positive group was higher than that of HPV-negative group (79% vs. 72%) but no significant difference was found ( P=0.09). The 5-year OS rate of patients whose tumor ≥ 3 cm (69%) was lower than those tumor < 3 cm (85%) and significant difference could be found ( P = 0.02). The 5-year OS rate of wild and moderate and poor grade were 85%, 70% and 58%, and significant difference could be found in the three groups ( P<0.01). The 5-year OS rates of patients with stage T 1a, T 1b, T 2, T 3and T 4 were 90%, 67%, 71%, 68% and 37% respectively( P<0.01). The 5-year OS rates of patients with stage N 0, N 1, N 2, and N 3 were 91%, 62%, 57%, and 30%, respectively( P<0.01). N stage could significantly affect the prognosis. The 5-year OS rate of T 1b patients was lower than that of T 1a and T 2 stage (67% vs. 90% vs. 71%, P=0.003). Of the 24 patients with T 1b stage, 17 cases received inguinal lymphadenectomy and 7 cases not. The 5-year OS rate of T 1b who received lymphadenectomy, who not and T 2 group were 73%, 57% and 71% respectively ( P=0.22). Multivariate Cox analysis showed that N stage ( HR =4.55, 95% CI 2.64-7.85, P<0.01) and tumor grade ( HR =2.09, 95% CI 1.09-4.02, P=0.03) were independent factors which could affect the prognosis. Conclusions:N stage and tumor grade were independent factors which could affect the prognosis. The poorer the tumor grade, the worse the prognosis. Inguinal lymphadenectomy could improve the prognosis of patients with T 1b stage.

Objective:To analyze germline pathogenic mutations in patients with upper tract urothelial carcinoma(age≤60 years old), and to explore the clinicopathological characteristics of germline pathogenic mutation carriers.Methods:The data of 124 patients (age≤60 years old) with upper tract urothelial carcinoma who underwent germline genetic testing at Fudan University Shanghai Cancer Center from September 2008 to February 2023 were retrospectively analyzed. There were 86 males and 38 females, and the median age was 55.0(49.8, 58.0)years old. The primary tumors were located in the renal pelvis in 81 cases (65.3%), the ureter in 34 cases (27.4%), and both in 9 cases (7.3%). There were 13 patients (10.5%) with low-grade UTUC and only 8 patients (6.5%) with carcinoma in situ. Twelve patients (9.7%) had a history of bladder cancer and 12 (9.7%) had a history of malignancy other than bladder cancer. Whole gene exome sequencing or target region sequencing was performed to explore germline mutations associated with patients with UTUC. The germline genetic testing data were interpreted in accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP)2015 edition guideline to clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Germline pathogenic mutation rates were further compared with those of healthy East Asian populations to analyze germline mutations associated with the risk of carcinogenesis in UTUC.Results:In this study, 31 germline pathogenic mutations were detected in 28 (22.6%) of 124 patients with UTUC. There were no statistically significant differences in age [54.0 (47.0, 58.0) years old vs. 56.0 (50.8, 58.0) years old], gender (male/female: 21/7 vs. 65/31), history of bladder cancer (0 vs. 12/96), T-stage (T 3-4: 12/28 vs. 41/96), and proportion of histologic high-level (26/28 vs. 85/96) between patients with and without germline pathogenic mutations ( P>0.05). The 31 germline pathogenic mutations were located in 22 genes, including BRCA2 (4, 12.9%), MSH2 (3, 9.7%), RAD54L (2, 6.5%), BRCA1 (2, 6.5%), BRIP1 (2, 6.5%), NOTCH3 (2, 6.5%), XRCC2 (1, 3.2%), VEGFA (1, 3.2%), TBX3 (1, 3.2%), RET (1, 3.2%), PRKN (1, 3.2%), PALB2 (1, 3.2%), NTRK1 (1, 3.2%), NCOA3 (1, 3.2%), MSH6 (1, 3.2%), LRP1B (1, 3.2%), KMT2D (1, 3.2%), KMT2A (1, 3.2%), FANCA (1, 3.2%), BARD1 (1, 3.2%), ARID1A (1, 3.2%), and AR (1, 3.2%). The germline pathogenic mutation rates of 124 patients were compared with those of the healthy East Asian population. The results showed that germline pathogenic mutations in BRCA2 ( OR = 11.9, 95% CI 3.8 - 37.7, P<0.001), MSH2 ( OR = 11.9, 95% CI 3.2-44.5, P<0.001), RAD54L ( OR=14.2, 95% CI 2.7-73.8, P=0.002) and BRCA1 ( OR=11.8, 95% CI 2.4-59.1, P=0.003) genes significantly increase the risk of developing UTUC. Conclusions:The rate of germline pathogenic mutations in ≤60 years old UTUC patients in this study was 22.6%, and germline pathogenic mutations carrying germline BRCA2, MSH2, RAD54L or BRCA1 genes significantly increased the risk of developing UTUC.