Photodynamic diagnosis in patients with T1G3 bladder cancer: influence on recurrence rate

Introduction

Therapeutic strategies on treatment of T1G3 urothelial cancer of the urinary bladder are controversial. The objective of this study was to investigate the impact of photodynamic diagnosis (PDD) on the recurrence-free survival rate of patients with the initial diagnosis of T1G3 bladder cancer.

Patients and methods

Between 1995 and 2007, 153 patients were treated for T1G3 bladder cancer at our institution. In 77 patients, initial TUR-BT was performed under PDD condition at our hospital, and 76 patients underwent TUR-BT in a standard white light setting at other institutions. PDD was performed either using 5-aminolevulinate or hexaminolevulinate for induction of fluorescence. Average follow-up was 53.9 months. Fisher’s exact test and Kaplan–Meier method were used to test data for significance.

Results

Of the 77 patients who were treated using PDD at initial TUR-BT, recurrence was observed in 23 (29.9%) cases, whereas 43 of 76 (56.6%) patients treated without PDD showed recurrence (P < 0.001). The detection rate of additional carcinoma in situ was 35.4% in the PDD group versus 21.8% in the white light group (P = 0.077). A limitation of the present study is the retrospective, monocentre setting, which is more likely to be biased.

Conclusion

PDD during initial TUR-BT in T1G3 bladder cancer seems to reduce significantly the rate of recurrence in our study population. Therefore, PDD seems to be associated with superior initial tumour control and more effective tumour treatment even in patients with highly aggressive tumours like T1G3 bladder cancer.     

T1G3膀胱癌187例临床分析及预后研究

目的 分析T1G3膀胱癌的临床特点及复发、进展、死亡的风险因素,提高对T1G3膀胱癌的认识和治疗效果. 方法 收集1998年1月至2006年10月天津市泌尿外科研究所诊断为T1G3膀胱癌且资料完整的患者187例.男162例,女25例.年龄35～92岁,平均66岁.进行临床流行病学调查并随访预后情况.寿命表法估计1、2、3、5年复发率、进展率及死亡率.将年龄、性别、出现症状至就诊时间、有无肾积水、手术方式、术后是否即刻灌药、膀胱灌注药物种类、肿瘤直径、肿瘤数量、肿瘤形态、有无原位癌、复发次数、初次复发时间≤6个月作为变量,分别进行肿瘤复发、疾病进展、死亡的Kaplan-meier单因素及Cox多因素生存分析. 结果 本组患者随访12～111个月,平均46个月.肿瘤复发100例(53.5％),进展61例(32.6％),死亡37例(19.8％).1、2、3、5年肿瘤复发率分别为35.0％、60.0％、63.0％、65.0％,疾病进展率分别为12.0％、27.0％、34.0％、38.0％,死亡率分别为0、11.0％、17.0％、26.0％.肿瘤直径、肿瘤数量、即刻灌注、初次复发时间≤6个月是T1G3膀胱癌复发的危险因素;肿瘤形态、原位癌、初次复发时间≤6个月、复发次数是T1G3膀胱癌进展的危险因素.肿瘤进展是患者死亡的危险因素. 结论 肿瘤直径≥3 cm、多发、初次复发时间≤6个月的T1G3膀胱癌患者更容易复发,应加强随访,即刻膀胱灌注可以降低T1G3膀胱肿瘤复发的风险.对肿瘤形态呈结节状、合并原位癌、初次复发时间≤6个月、多次复发等进展高危风险因素的T1G3膀胱肿瘤患者,应早期行膀胱切除.     

Prognostic significance of non-papillary tumor morphology as a predictor of cancer progression and survival in patients with primary T1G3 bladder cancer

Objective  To investigate the prognostic significance of tumor morphology in relation to progression and survival in patients with primary T1G3 bladder cancer (BC) Methods  After review of pathology, 194 patients who were diagnosed with primary T1G3 BC after clinically complete transurethral resection between 1989 and 2005 were seen. Of these patients, 144 underwent surveillance and 50 underwent immediate cystectomy. Tumor morphology (gross and microscopic) in addition to other clinicopathological factors such as tumor size, multifocality, lymphovascular invasion (LVI), carcinoma-in-situ (CIS), intravesical therapy, and the absence of proper muscle were evaluated with regard to recurrence, progression, upstaging, and survival. In addition, correlations between tumor morphology and other factors were analyzed. Results  Median follow-up was 52.5 months. Five-year cancer-specific survival rates were 92.1% for entire cohort, 95.6% for surveillance group, and 84.0% for immediate cystectomy group, respectively. During surveillance, recurrence and progression were noted in 43.1, 13.2%, respectively. Of the potential prognostic factors analyzed, non-papillary morphology (both gross and microscopic) was a significant parameter of progression and intravesical therapy was significantly predictive of recurrence. After immediate cystectomy, 34% were upstaged. Non-papillary morphology and the absence of proper muscle were related to upstaging. For entire patients, non-papillary morphology and the absence of proper muscle were also significant predictors of patient’s survival (P = 0.048, HR = 4.826, and P = 0.007, HR = 5.663, respectively). Non-papillary tumors were significantly related to the presence of LVI and CIS compared to papillary tumors. Conclusions  Non-papillary tumor morphology was a predictor of cancer progression and survival in patients with primary T1G3 BC.     

Prediction of recurrence and progression in patients with T1G3 bladder cancer by gene expression of circulating tumor cells

ObjectiveTo investigate the role of gene expression of circulating tumor cells (CTCs) as noninvasive prognostic markers in patients with high risk nonmuscle invasive bladder cancer.Materials and methodsWe identified all patients with TIG3 urothelial bladder cancer (UBC) at our institution since 2016.The study included 100 patients with T1G3 UBC and 50 healthy volunteers. CTCs were isolated from blood using immunomagnetic separation and gene expression was performed using 10 bladder cancer associated genes, namely; KRAS, EPCAM, CD133, CD44, mTOR, SURVIVIN, AKT, PI3K, VEGF, and TP53. Gene expression of CTCs was correlated to time to first recurrence and time to progression using Kaplan-Meier curves.ResultsThere was strong negative correlation between CTCs-positive patients and time to first recurrence and time to progression. Significant differences in expression levels of specific genes were observed that can predict recurrence and progression of T1G3 UBC.ConclusionCTCs appear to be noninvasive methods of predicting disease recurrence and progression in patients with high- risk nonmuscle invasive bladder cancer; therefore, studying their molecular profiling may improve prediction of recurrence and progression. Further studies are invited for more in-depth investigation to consolidate our initial results.     

A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence,progression and survival

PURPOSE: We retrospectively evaluated the long-term outcome in patients with newly diagnosed stage T1 grade 3 bladder cancer treated with transurethral resection with or without intravesical bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Of 153 patients with a median age of 67 years (range 36 to 88) and a male-to-female ratio of 4:1 we treated 92 with transurethral bladder resection and additional BCG, and 61 with transurethral bladder resection alone. BCG was administered intravesically as 120 mg. BCG Pasteur F dissolved in 50 ml. saline, retained for up to 2 hours weekly for 6 weeks and repeated as necessary. RESULTS: Median followup was 5.3 years (range 0.4 to 18.2). Disease recurred in 70% of the patients treated with BCG and in 75% treated with transurethral resection alone. Median time to recurrence was 38 and 22 months for BCG and resection alone (p = 0.19). Tumor progressed in 33% of patients with BCG and in 36% with resection alone. Deferred cystectomy was performed in 29% of the patients with BCG and in 31% with resection alone. Overall and disease specific survival did not differ significantly. CONCLUSIONS: Our results suggest that intravesical BCG therapy after transurethral bladder resection for stage T1 grade 3 bladder cancer may delay the time to recurrence and cystectomy but it does not substantially alter the final outcome. Our findings reflect the rule of 30% for stage T1 grade 3 cancer, namely approximately 30% of patients never have recurrence, 30% ultimately die of metastatic disease and 30% require deferred cystectomy.