Preoperative whole pelvis versus true pelvis irradiation and/or cystectomy for bladder cancer

Between 1949 and 1974, 449 patients with bladder cancer were treated by radical cystectomy either alone (137 patients or following three preoperative radiation schemes (312 patients). True pelvis irradiation was delivered either 4000 cGy (rad) over 4 weeks in 119 patients, or 2000 cGy over 1 week in 86 patients; radical cystectomy was performed after periods averaging 6 weeks.and 2 days, respectively. Whole pelvic irradiation of 2000 cGy in 5 consecutive days was given to 107 patients who underwent cystectomy within 2 days later. Five-year survival rates for low-stage TIS-T₂ tumors of low histologic grade were 60–66% in the four treatment groups. The 5-year survival for high-stage tumors of high histologic grade, mainly in T₃ patients, was 9% in the cystectomy alone patients versus 24–32% in the preoperatively irradiated patients. The 5-year survival rates for high-stage low-grade and low-stage high-grade tumors, were 30% in the cystectomy alone group and 39–51% in the preoperative irradiation groups; the more favorable survival was noted in the whole pelvic irradiation group, which included 18% 5-year survivals for T₄ patients. Pelvic recurrence was reduced from 28% after cystectomy alone to 14–16% with true pelvis irradiation and 8% with whole pelvic irradiation. The reduced incidence of local recurrence, observed mainly in high stage or high grade tumors, was associated with tumor downstaging after irradiation. Extrapelvic metastases developed in 21–35% of the four treatment groups, underlining the inadequacy of the local radiation and surgical treatment in preventing subsequent distant spread.     

Carcinoma of the urinary bladder T3NxMo treated by preoperative irradiation followed by simple cystectomy

One hundred eighty-three patients with bladder cancer category T₃N_xM_o (the diameter of the primary exceeding 5 cm), were treated by preoperative 40 Gy and simple cystectomy. Using only pretreatment information, the group with the best prognosis was characterized by a T,,-growth with a normal intravenous pyelography, with about a 75% cure rate. Before cystectomy, after irradiation the combination of a clinically assessed radiation-downstaged growth (T_40GY < 3) with normal urography, predicted the best chance of cure at about 80%. After cystectomy was performed, the best prognostic group could be most correctly identified: those patients with both microscopic downstaging of the primary (“P”_<3) and no vascular invasion in the cystectomy specimen (CV?) combined with normal urography had an 81% chance of cure. This most favorable group constitutes 45% of all patients.     

Factors of prognostic and therapeutic significance in patients with bladder cancer

In a two-decade period, 451 patients with bladder cancer were treated by external megavoltage irradiation and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was performed in 137 patients. One-hundred nine patients underwent radical cystectomy for cancer recurrence or persistence ± 1 year after radical irradiation averaging 6000 red tumor dose in 6 weeks. Planned preoperative pelvic irradiation either 4000 rad in 4 weeks in 119 patients or 2000 rad in 1 week in 86 patients was followed by radical cystectomy after average intervals of 6 weeks and 2 days, respectively. Similarly more favorable 5-year survival results were observed with prior radial (41 %) or preoperative conventional (43 %) or shorter regimen (42 %) irradiation than with cystectomy alone (33%); especially in high clinical stage B₂-D₁ tumors (27–37% with versus 14% without irradiation), in lesions not larger than 4 cm (50–57 % versus 38 % ), in patients older than 60 years (39–43 % versus 28 % ), in female patients (38–50 % versus 26 %), and in patients who had prior therapeutic tumor resections (41–45% versus 27%). Less favorable 5-year survival results were noted in the four treatment groups (with and without irradiation), in patients with precystectomy obstructive uropathy (28 % ) than in those with normal excretion urograms (46 % ), with tumors larger than 4 cm (26 %) than with smaller lesions (48 % ), with solid (33 %) than with papillary (51 %) tumors, with solitary (36%) than with multifoal (46%) cancers, and in cases with vascular tumor thrombi in the operative specimen (14 %) than in cases without tumor thrombi (41 %).     

Planned preoperative irradiation in the management of clinical stage B2-C (T3) bladder carcinoma

In recent years the role of planned preoperative irradiation in the management of clinical Stage B2-C (T3) bladder cancer has been questioned by a number of investigators. Much of the confusion regarding the efficacy of combined therapy results from studies that compare the results of treatment of pathological Stage B2-C patients treated by cystectomy alone versus clinical Stage B2-C patients treated by preoperative irradiation plus cystectomy. Such comparisons are biased because of (1) the exclusion of a large number of Stage D patients from cystectomy-alone series and their inclusion in preoperative irradiation plus cystectomy series and (2) the inclusion in the cystectomy-alone series of patients whose clinical stages were less than or equal to T2. The purpose of this paper is to compare the results of treatment in patients with clinical Stage B2-C bladder carcinoma following radical cystectomy alone versus preoperative irradiation plus cystectomy. This article reviews the rationale for administering preoperative irradiation, the effect of preoperative irradiation on the pathological specimen (including down-staging, the effect on regional lymph nodes, and radioresponsiveness according to tumor configuration, i.e., papillary vs. solid), the impact of preoperative irradiation on pelvic recurrence and 5-year survival, and the effect of preoperative irradiation on operative and postoperative complications. This paper cites all known literature on the subject in the English language. Data comparing 5-year survival results between radical cystectomy alone versus preoperative irradiation plus cystectomy are analyzed in three different ways: (a) retrospective comparisons of historical results, (b) review of the results of 6 randomized trials, and (c) comparison of concomitantly treated "modern-day" (1960-1980) series treated by either radical cystectomy alone versus preoperative irradiation plus cystectomy in 1185 patients. Preoperative results are also analyzed according to dose level (2000 rad versus 4000 rad versus 4500-5000 rad). The data presented indicate that the addition of preoperative irradiation to cystectomy for clinical Stage B2-C (T3) bladder cancer adds approximately 15 to 20 percentage points to the 5-year survival, leading to a survival figure that is approximately half-again that achieved by cystectomy alone.     

Patterns of recurrence in bladder cancer treated by irradiation and/or cystectomy

Between 1949 and 1971, 451 patients with bladder cancer were treated by radiation therapy and/or radical cystectomy at the Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment for 137 patients in Group 1. In Group 2, 109 patients received radiation therapy to an average tumor dose of 6000 rad in 6 weeks ± 1 year before radical cystectomy for persistent, recurrent or new lesions. Planned preoperative irradiation consisted of either 4000 rad in 4 weeks for 119 patients in Group 3, or 2000 rad in 1 week for 86 patients in Group 4, ± 6 weeks and 2 days, respectively, before radical cystectomy.The determinate over-all distant and/or local recurrence rate was 49% for Group 1 and 37–45% for Groups 2–4. Local recurrence alone occurred in 28% of Group 1 patients and 14–16% of those in Groups 2–4. Distant metastases developed in 21% of Group 1 patients and 22–28% of Group 2–4 patients. A reduced incidence of pelvic recurrence was associated with radiation-induced stage reduction for Group 2–4 clinically high and low stage tumors, especially when the histologic grade was high. Similar frequencies of extrapelvic metastases in the four groups were maintained in clinically low and high stage tumors of low or high histological grade.     

Flow cytometric analysis of DNA content in human bladder tumors and irrigation fluids

Flow cytometry (FCM) was used to study the DNA distribution of 99 tumor biopsy specimens and 41 bladder irrigation samples from patients with transitional cell carcinoma of the bladder. For tumor biopsy and cystectomy specimens, the frequency of aneuploidy increased with advancing tumor stage and grade. All T0 tumors were diploid. Twenty-seven percent of T1, 71.4% of T2, and 75% of T3 and T4 tumors were aneuploid. All Grade I tumors were diploid. Thirty percent of Grade II and 76.9% of Grade III tumors were aneuploid. The frequency of aneuploidy of tumors in the early stages (Ta, T1) is similar to the incidence of subsequent progression by these tumors described in the literature. For irrigation fluids, the relationship between grade and stage and the frequency of aneuploidy was similar to the relationship seen with tumor specimens. All four patients with only carcinoma in situ had aneuploid cells in their irrigations. The comparison of FCM data of bladder biopsy and bladder irrigation from the same cystoscopic evaluation suggests adequate representation of tumor cells in the irrigation fluids for almost all cases. The authors conclude that DNA ploidy analysis by FCM appears useful in a clinically important group of patients with aneuploid superficial tumors of moderate or high grade. Bladder irrigation analysis appears useful in the follow-up of patients with a history of carcinoma in situ and those with aneuploid tumors.     

Integrated preoperative irradiation and radical cystectomy

Thirty patients with stage B₂-C-D₁ and/or grade II–IV transitional cell carcinoma of the bladder were entered into a pilot study of integrated surgery and radiotherapy. Staging laparotomy with formation of an Real loop preceded the delivery of 4000–5000 rad in 4–5 weeks to the pelvis; cystectomy was accomplished in 26 patients 4–8 weeks after completion of irradiation. The program was accomplished without undue difficulty and resulted in a lowering of the clinical stage in 22 of 26 patients; no residual invasive cancer was seen histologically in 8 patients. Although it was formidable, the morbidity rate was not significantly different than it was after cystectomy without preoperative irradiation. The short term survival rate, in conjunction with an analysis of sites of failure, suggests that a prospective study be accomplished to document the validity of this therapeutic approach to bladder cancer; patient selection, surgical technique, and time-dose-volume radiation factors should also be considered.     

Radical cystectomy for bladder cancer:oncologic outcome in 271 Chinese patients

Few large scale studies have reported the oncologic outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who underwent radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months(range, 0.2–139.1 months). Thirty-day mortality was(1.4%). The 5-year recurrence-free survival, cancer-specific survival(CSS), and overall survival rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of patients with T1–T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS rate than those with extravesical disease(81.4% vs. 34.9%, P 0.001). For the 38 patients(14%) with lymph node involvement, the 5-year CSS rate was 27.7%—significantly lower than that of patients without lymph node metastasis(P 0.001). The 5-year CSS rate was much higher in patients with low grade tumor than in those with high grade tumor(98.1% vs. 68.1%, P 0.001). Multivariate Cox regression showed that patient age(hazard ratio, 2.045; P = 0.013) and T category(hazard ratio, 2.213; P 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. Old age and high T category were associated with poor prognosis in bladder cancer patients who underwent radical cystectomy.     

Prognostic implications of downstaging following preoperative radiation therapy for operable T3–T4 rectal cancer

Purpose: To evaluate the prognostic value of tumor downstaging after preoperative radiation for resectable rectal cancer.

Methods and Materials: Eighty-eight patients with non-metastatic resectable rectal cancers (76 T3 and 12 T4) were treated with preoperative irradiation. Median dose was 40 Gy (30–46 Gy) delivered over 32 days (range 11–40). Seventeen patients received preoperative chemotherapy, two courses of 5-fluorouracil (5FU) 350 mg/m²/day and folinic acid 20 mg/m²/day; 5 days per week during the first and fifth weeks of radiotherapy. Surgery was performed with a mean delay of 46 days after completion of irradiation and included 66 abdominoperineal resections and 22 anal sphincter-preserving procedures. Postoperative chemotherapy was administered in 44 patients.

Results: Histological tumor stages were: complete histological response in 7%, pT2N0 in 19%, pT3N0 in 46%, and pT2-3N1 in 28%. Tumor downstaging occurred in 26%. No predictive factor of downstaging was statistically significant. The median follow-up was 33 months. The 3- and 5-year cancer-specific survival rates were 100% for the pT0N0 and pT2N0, respectively, 89% and 68% for pT3N0, and 64% and 0% for pT2T3N1. After preoperative irradiation, the pathological tumor stages remained a prognostic factor. Patients with downstaging (pT0T2N0) had significantly higher cancer-specific survival rates than the group without downstaging: 100% and 80% at 3 years, and 100% and 45% at 5 years; respectively (p = 0.011). The 3- and 5-year recurrence free-survival rates were 94% for the group with downstaging and 56% and 50%, respectively, for the group without downstaging (p = 0.002).

Conclusion: Downstaging after preoperative irradiation in this retrospective study results in an improvement in local control and survival.     

Postdiversion precystectomy irradiation for cancer of the bladder.

This is the first report of a 4-year prospective trial of integrated irradiation and cystectomy in the management of advanced bladder carcinoma. Patients are treated sequentially with staging laparotomy and urinary diversion, highdose preoperative irradiation (5,000 rad/30 treatments/42 days), and total cystectomy. Twenty-eight consecutive patients have been entered into the study; all had Grade III or IV tumor or clinical evidence of invasion (Jewett Stage B1-D1). Local control has been achieved in 21 of 22 patients, and the 4-year actuarial survival is 54%. The initial staging procedure not only defines inoperable patients, but also allows completion of urinary diversion prior to small bowel irradiation with fewer anastomotic problems. Acute and chronic complications have been minimal, and there have been no treatment-related deaths.     

Evaluation for surrogacy of end points by using data from observational studies: tumor downstaging for evaluating neoadjuvant chemotherapy in invasive bladder cancer.

PURPOSE: In clinical cancer trials for evaluating neoadjuvant chemotherapy, tumor downstaging is frequently used as a surrogate end point for overall survival. We evaluated the surrogacy of tumor downstaging using data from a follow-up observational study in bladder cancer. EXPERIMENTAL DESIGN: A total of 586 patients (from 32 Japanese hospitals) who underwent radical cystectomy for invasive bladder cancer (clinical T2 to T4) between 1990 and 2000 were analyzed. We considered changes over time in clinical stage at diagnosis and pathologic stage at cystectomy as a surrogate end point, and survival time after cystectomy as a true end point. First, we developed a new criterion for tumor downstaging. Second, we statistically evaluated surrogacy for the criterion using Prentice's criteria. RESULTS: To develop the criterion of end points based on tumor downstaging, we selected the best classification among all possible classifications in an attempt to separate prognosis for patients. The hazard ratios after adjustment for prognostic factors in the intermediate effect patients and the poor effect patients were 1.9 (95% confidence interval, 1.0-3.7) and 5.0 (95% confidence interval, 2.6-9.8), respectively, compared with that in the good effect patients. The conditions for correlation and conditional independency of Prentice's criteria were satisfied approximately. Neoadjuvant chemotherapy has a statistically significant tumor downstaging effect, whereas there was no difference on survival between treatment groups. CONCLUSIONS: The tumor downstaging effect could be an appropriate intermediate end point for screening novel neoadjuvant chemotherapy for invasive bladder cancer. The dataset from follow-up studies were useful for evaluating the surrogacy of end points.     

Flow cytometric DNA analysis of medulloblastoma. Prognostic implication of aneuploidy

Paraffin-embedded surgical specimens from 26 infants and children with medulloblastomas treated between 1972 and 1981 were examined for DNA ploidy by flow cytometry (FCM). All patients received a standard treatment (a combination of maximum debulking of medulloblastoma and postoperative craniospinal irradiation with a posterior fossa boost of 5000 rad or more). They were studied to correlate the results of the findings of FCM DNA analysis with their final outcome, DNA ploidy, and extent of tumor resection. All seven patients with totally resected aneuploid medulloblastoma are alive, whereas only one of six patients with subtotally resected diploid medulloblastoma is alive (P = 0.0047). The current study suggests both DNA ploidy and extent of surgical resection are the most important determinant of patients' prognosis. Patients in selected group, particularly those with subtotally resected diploid tumor, are advised to undergo aggressive adjuvant chemotherapy.     

Factors influencing the prognosis in bladder cancer

In the categories T1, T2 and T3NxM0 bladder cancer, diameter not exceeding 5 cm, the treatment in the Rotterdam Radio-Therapy Institute consists of interstitial irradiation with needles containing radioactive material. The results of treatment and the role of additional external irradiation are discussed. Category T3NxM0 tumors diameter exceeding 5 cm are treated by external irradiation followed by cystectomy; the results are presented here. Factors influencing prognosis appeared to be degree of differentiation, number of transurethral resections (TURs) prior to definitive treatment, intravenous pyelography (IVP), vascular invasion, T category after preoperative irradiation, and postsurgical histopathologically-assessed T category (pT).     

Combined treatment of rectal cancer

In 15 males and 25 females at the age of 24--70 the authors have studied radiation pathomorphosis, the early and late results in anal and low ampullar cancer following preoperative large fractionation irradiation on a gamma-therapeutic machine "Rokus" with the rotation regime of 400--600 rad daily, a total dosage--2000--3000 rad. The operation was performed 2--3 days following the irradiation. Eighteen patients were followed up over 3 years. Recurrences and metastases were noted in 5 cases (glandular-solid and mucosa forms of cancer). A 3-year survival was 72.2% versus 40.7% (P less than 0.001) while using surgical therapy solely.     

Progression and survival in prostatic adenocarcinoma: a comparison of clinical stage, Gleason grade, S-phase fraction and DNA ploidy.

Clinical data were reviewed in 325 patients with prostatic adenocarcinoma followed up for a mean of 13 years. Paraffin-embedded tumour biopsy specimens from the primary tumours were available for flow cytometry (FCM) in 273 cases. Intra-tumour heterogeneity in DNA index (DI) was found in 4% of the tumours (54 cases were analysed). S-phase fraction (SPF) and DNA ploidy were significantly interrelated. Aneuploidy and high SPF were significantly related to both a high T category and high Gleason score. The progression in T1-2M0 tumours was related to Gleason score (P = 0.009), DNA ploidy (P = 0.006) and SPF (P = 0.007), while the Gleason score (P = 0.0013), DNA ploidy (P = 0.002) and SPF (P < 0.001) had prognostic value in univariate survival analysis. In the entire cohort, the T category (P < 0.001), M category (P < 0.001), Gleason score (P < 0.001), DNA ploidy (P < 0.001) and SPF (P < 0.001) were significant prognostic factors. In Cox''s analysis, the M category (P < 0.001), Gleason score (P < 0.001), T category (P = 0.003), age (P = 0.001) and SPF (P = 0.087) were independently related to prognosis. In the T1-2M0 tumours, Gleason score (P < 0.001), T category (P = 0.022) and SPF (P = 0.058) were independent predictors. A novel classification system in which the DNA ploidy or SPF and the Gleason score were combined was found to be of significant prognostic value in all M0 tumours (P < 0.001). The results suggest that FCM can be used as an adjunct to conventional histological assessments for determination of the correct prognostic category in prostatic adenocarcinoma.     

Transitional cell carcinomas of the urinary bladder. Effects of preoperative irradiation on morphology

The effects of preoperative irradiation on the morphology of transitional cell carcinomas (TCCs) were evaluated by studying the pretreatment biopsy and radical cystectomy specimens from 35 patients. Twenty-six of these patients had received 2000 rad within the week preceding surgery, and nine patients had received no preoperative treatment. The frequency of bladders without residual TCC was 23% for irradiated and 22% for nonirradiated cases. Of the TCCs classified as papillary in the biopsy specimens and irradiated, 79% lacked a papillary component at cystectomy, but in no case was the invasive component eliminated or regression from muscle invasion to superficial TCC noticed. Flat carcinoma in situ (CIS) did not respond to irradiation. At cystectomy nuclear pleomorphism was greater than at biopsy in 60% of the irradiated TCCs, whereas all nonirradiated cases retained the same grade as at biopsy. In addition, irradiation induced squamous differentiation in neoplastic cells only, without affecting the nonneoplastic urothelium.     

Prediction of mesorectal nodal metastases after chemoradiation for rectal cancer: results of a randomised trial: implication for subsequent local excision.

BACKGROUND AND PURPOSE: For patients with rectal cancer treated with full thickness local excision the risk of mesorectal nodal metastases has to be very low. The aim was to assess this risk after preoperative radiotherapy in relation to pathological T-category. PATIENTS AND METHODS: Three hundred sixteen patients with resectable cT3-4 low rectal carcinoma were randomised to receive either pre-operative 5 x 5 Gy irradiation with subsequent surgery performed within 7 days or chemoradiation (50.4, 1.8 Gy per fraction plus bolus 5-fluorouracil and leucovorin) followed by surgery after 4-6 weeks. The pathological reports of patients who fulfilled entry criteria and had preoperative irradiation followed by transabdominal surgery were analysed. RESULTS: Significant downstaging of primary tumour (P<0.001) and of nodal disease (P=0.007) was observed after chemoradiation in comparison with short-course irradiation. In chemoradiation group, for patients with complete pathological response and for ypT1 category, the rate of nodal metastases was low - 5% (95% confidence interval [CI] 0-14%) and 8% (95% CI 0-24%), respectively. The rate of ypN-positive disease in chemoradiation group was similar to that recorded in short-course irradiation group for ypT2 category 26% (95% CI 14-38%) vs. 28% (95% CI 16-40%), P=0.83 and for ypT3-4 category 55% (95% CI 41-69%) vs. 64% (95% CI 54-74%), respectively, P=0.37. For ypT2 category after chemoradiation, the rate of nodal disease remained high even in subgroup with low residual cancer cells density (20%, 95% CI 4-36%). CONCLUSIONS: For patients with tumours downstaged by chemoradiation to ypT0 and ypT1 full thickness local excision may be considered as an acceptable approach, because the risk of mesorectal lymph nodes metastases is low. The selection criteria for preoperative radio(chemo)therapy and local excision are discussed.     

Guanine nucleotide‐binding protein 1 is one of the key molecules contributing to cancer cell radioresistance

Standard fractionated radiotherapy for the treatment of cancer consists of daily irradiation of 2‐Gy X‐rays, 5 days a week for 5–8 weeks. To understand the characteristics of radioresistant cancer cells and to develop more effective radiotherapy, we established a series of novel, clinically relevant radioresistant (CRR) cells that continue to proliferate with 2‐Gy X‐ray exposure every 24 h for more than 30 days in vitro. We studied three human and one murine cell line, and their CRR derivatives. Guanine nucleotide‐binding protein 1 (GBP1) gene expression was higher in all CRR cells than their corresponding parental cells. GBP1 knockdown by siRNA cancelled radioresistance of CRR cells in vitro and in xenotransplanted tumor tissues in nude mice. The clinical relevance of GBP1 was immunohistochemically assessed in 45 cases of head and neck cancer tissues. Patients with GBP1‐positive cancer tended to show poorer response to radiotherapy. We recently reported that low dose long‐term fractionated radiation concentrates cancer stem cells (CSCs). Immunofluorescence staining of GBP1 was stronger in CRR cells than in corresponding parental cells. The frequency of Oct4‐positive CSCs was higher in CRR cells than in parental cells, however, was not as common as GBP1‐positive cells. GBP1‐positive cells were radioresistant, but radioresistant cells were not necessarily CSCs. We concluded that GBP1 overexpression is necessary for the radioresistant phenotype in CRR cells, and that targeting GBP1‐positive cancer cells is a more efficient method in conquering cancer than targeting CSCs.     

Quantifying the Overall Survival Benefit With Early Radical Cystectomy for Patients With Histologically Confirmed T1 Non–muscle-invasive Bladder Cancer

IntroductionThe objective of this study was to examine the overall survival (OS) in patients diagnosed with high-grade T1 non–muscle-invasive bladder cancer treated with early radical cystectomy versus local treatment of the primary tumor, defined as endoscopic management with or without intravesical chemotherapy or immunotherapy.Patients and MethodsWe identified 4900 patients with histologically confirmed, clinically non-metastatic high-grade T1 bladder cancer undergoing surgical intervention using the National Cancer Database for the period 2010 to 2015. Multivariable logistic regression was used to examine predictors for the receipt of early radical cystectomy (defined as radical cystectomy within 90 days of diagnosis). We then employed multivariable Cox proportional hazards regression models and Kaplan-Meier curves to evaluate the OS according to surgical treatment (early radical cystectomy vs. local treatment).ResultsA minority (23.7%) of patients underwent early radical cystectomy. Independent predictors of undergoing early radical cystectomy included lower age, White race, and lower comorbidity status. The median OS was 74.0 months for patients diagnosed with high-grade T1 bladder cancer. The 1- and 5-year survival rates of patients undergoing early radical cystectomy were 94.8% and 71.0%, whereas they were 85.2% and 52.4%, for patients undergoing initial local treatment, respectively (P < .001). Compared with patients undergoing local treatment, patients undergoing early radical cystectomy had a lower risk of all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.67-0.91; P = .002).ConclusionIn this cohort of patients presenting with high-grade T1 non–muscle-invasive bladder cancer, we found that early radical cystectomy was associated with an OS benefit compared with initial local treatment.     

Conservation of bladder function in patients with invasive bladder cancer treated by definitive irradiation and selective cystectomy

Four hundred seventy patients with invasive bladder cancer treated by definitive irradiation (5000 rad or more) and selective cystectomy were followed to assess their survival status and bladder function status. (90 % were followed for at least 10 years or to death.) The survival rates for these patients were similar to those obtained in studies of preoperative irradiation with compulsory cystectomy: 5 and 10 year survival rates were 38 and 22% respectively. Sixty-five to 70% of these survivors lived with healthy, functioning bladders to at least 10 years after treatment. Seventy-five patients had a selective cystectomy, usually for recurrent disease, with an operative mortality rate of 11 %. Pre-irradiation catheterization, used to control bladder distension and to reduce the possibility of geographic miss in irradiating the tumour, had no effect on the control of local disease or on the long-term survival of patients. Therefore, definitive irradiation with selective cystectomy warrants serious consideration in treating patients with invasive bladder cancer, especially considering the quality of life and the high proportion of patients who retain functioning bladders.