Salvage cystectomy after failure of interstitial radiotherapy and external beam radiotherapy for bladder cancer

OBJECTIVE: To evaluate the long-term results of salvage cystectomy after interstitial radiotherapy (IRT) and external beam radiotherapy (EBRT) for transitional cell carcinoma, and to assess the morbidity and functional results of the different urinary diversions used. PATIENTS AND METHODS: The records of 27 patients treated with salvage cystectomy in one institution between 1988 and 2003 were retrospectively analysed. RESULTS: Salvage cystectomy was used after failure of IRT in 14 or EBRT in 13 patients, with a 3- and 5-year survival probability of 46% (95% confidence interval 26-65) and 33 (11-54)%. The 5-year overall survival after cystectomy was 54% after IRT and 14% after EBRT (P = 0.12). Tumour category, response to radiation, American Society of Anesthesiology score, and complete tumour resection had a significant influence on survival. Five of seven patients with incomplete resection died because of local disease, with a median survival of 5 months. There was clinical understaging after radiotherapy in 41% of patients. Nine patients had an orthotopic neobladder, with complete day- and night-time continence in eight and four, respectively. All patients but one had good voiding function. There were early complications in two and late complications in six patients (for Bricker, seven of 14 and none; for Indiana, none of four and two of four). The duration of hospitalization was not influenced by the type of diversion. Erectile function was maintained in four of six patients after a sexuality-preserving cystectomy and neobladder. CONCLUSIONS: Salvage cystectomy can be performed with acceptable morbidity using any type of urinary diversion. Understaging after radiotherapy is common, but preoperative selection needs improving. A very significant factor for an adverse outcome and death from local tumour recurrence was incomplete resection, suggesting that salvage cystectomy should only be attempted if complete resection is probable.     

Impact of sarcopenia in bladder preservation therapy for muscle-invasive bladder cancer patients: a narrative review

Background and ObjectiveMuscle-invasive bladder cancer (MIBC) is a biologically aggressive disease and its prognosis is poor. Radical cystectomy (RC) with urinary diversion and lymph node dissection is the gold standard treatment for MIBC patients. Accumulating evidence indicates that sarcopenia, the degenerative and systemic loss of skeletal muscle mass, is a significant predictor of higher rates of mortality and perioperative complications following RC. Recently, bladder preservation therapy has been offered as an alternative in appropriately selected MIBC patients who desire to preserve their bladders and those unfit or unwilling for RC. Here, we performed a narrative review on the impact of sarcopenia on oncological outcomes and complication rates in MIBC patients treated with bladder preservation therapy.MethodsA literature review was performed using the PubMed and Scopus databases.Key Content and FindingsWe identified two studies reported the impact of sarcopenia on responses to trimodal therapy and survival outcomes in MIBC patients. Consolidative partial cystectomy was performed in patients who achieved clinical complete response (CR) to trimodal therapy in one of the two studies. In both studies, CR rates to trimodal therapy are comparable between sarcopenic and non-sarcopenic patients. Sarcopenia was not significantly associated with shorter survival after completing bladder preservation therapy in either study. For complication rates of bladder preservation therapy, one study showed equivalent complication rates of consolidative partial cystectomy between sarcopenic and non-sarcopenic patients. In addition, in another small series of trimodal therapy, sarcopenic patients showed a higher rate of complications of trimodal therapy compared with non-sarcopenic patients.ConclusionsAccording to the result of our literature review, sarcopenia would not affect responses to trimodal therapy and prognosis in MIBC patients treated with bladder preservation therapy. Although the effect of sarcopenia on complication rates of bladder preservation therapy is inconclusive due to limited evidence, bladder preservation therapy could be a viable alternative option in carefully selected MIBC patients regardless of the presence of sarcopenia.     

Impact of age on quality of life in patients with localized prostate cancer treated with high‐dose rate brachytherapy combined with external beam radiotherapy

Objectives

To evaluate age‐related quality of life changes in patients with localized prostate cancer treated by high‐dose rate brachytherapy combined with external beam radiation therapy.

Methods

A total of 172 patients with clinically localized prostate cancer were categorized to age groups <75 years and ≥75 years. Changes in their quality of life were evaluated using the Japanese version of Medical Outcome Study 8‐Items Short Form Health Survey, Expanded Prostate Cancer Index Composite and International Index of Erectile Function‐5 at baseline, and followed up to 24 months after treatment.

Results

There were no significant differences in Medical Outcome Study 8‐Items Short Form Health Survey scores, and urinary and bowel scores of the Expanded Prostate Cancer Index Composite for older men after treatment. International Index of Erectile Function‐5 summary scores were significantly decreased in both groups. Although sexual function and sexual bother scores were decreased in patients aged <75 years, these scores were maintained in patients aged ≥75 years.

Conclusions

Quality of life of prostate cancer patients undergoing high‐dose rate brachytherapy combined with external beam radiation therapy does not seem to be significantly affected by age.     

Secondary cancers after intensity‐modulated radiotherapy,brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause‐specific survival outcomes according to the initial treatment intervention

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis.

OBJECTIVE

• ? To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP).

MATERIALS AND METHODS

• ? Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP (n= 1348), EBRT (n= 897) or BT (n= 413).
• ? Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs.

RESULTS

• ? The 10‐year SM‐free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P= 0.002; RP vs BT, P= 0.37).
• ? The 10‐year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively (P= 0.29).
• ? Multivariate analysis of predictors for development of all SMs showed that older age (P= 0.01) and history of smoking (P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable.
• ? Among 243 patients who developed a SM, the 5‐year likelihood of SM‐related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P= 0.052).

CONCLUSIONS

• ? The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history.
• ? The incidence of bladder and rectal cancers was low for both EBRT‐ and BT‐treated patients.
• ? Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts.

     

Relationship of frailty with treatment modality selection in patients with muscle-invasive bladder cancer (FRART-BC study)

BackgroundWe aimed to investigate the association of frailty with treatment selection in patients with muscle-invasive bladder cancer (MIBC) as frailty is one of the key factors for modality selection.MethodsWe retrospectively evaluated frailty in 169 patients with MIBC from January 2014 to September 2020 using the Fried phenotype, modified frailty index, and frailty discriminant score. The primary purpose was comparing the frailty between the patients who underwent radical cystectomy (RC) with those who had trimodal therapy (TMT) for bladder preservation. Secondary purposes were comparing the frailty between the groups and the effect of TMT on overall survival adjusting the frailty by multivariate Cox proportional hazards analysis using inverse probability of treatment weighting (IPTW)-adjusted model.ResultsOf 169 patients, 96 and 73 were classified into the RC and the TMT groups, respectively. The median age of the TMT group was significantly higher than that of the RC group (80 vs. 69 years). Frailty levels and prevalence in the Fried phenotype, modified frailty index, and frailty discriminant score were significantly higher in the TMT group than those in the RC group. Logistic regression analysis showed that frailty was significantly associated with the TMT selection. Overall survival was significantly shorter in the TMT group by the IPTW-adjusted Cox regression analysis (hazard ratio 2.48, P=0.043).ConclusionsFrailty was significantly different between the RC and TMT in patients with MIBC and might be one of the key factors for treatment selection.     

C-reactive protein level predicts prognosis in patients with muscle-invasive bladder cancer treated with chemoradiotherapy

OBJECTIVE

To investigate the effect of C‐reactive protein (CRP) level on the prognosis of patients with muscle‐invasive bladder cancer treated with chemoradiotherapy (ChRT), as it is increasingly recognized that the presence of a systemic inflammatory response is associated with poor survival in various malignancies.

PATIENTS AND METHODS

The clinical records of 88 patients with bladder urothelial carcinoma (cT2–4 N0M0) treated with ChRT were reviewed retrospectively. ChRT comprised external beam radiotherapy to the bladder (40 Gy) with two cycles of cisplatin (50–100 mg) at 3‐week intervals. Elevated CRP was defined as >0.5 mg/dL. The survival rate was calculated using the Kaplan‐Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model.

RESULTS

During the median (range) follow‐up of 33 (3–117) months, 19 patients died from bladder cancer; the 5‐year cancer‐specific survival (CSS) rate was 73%. Ten patients had a high CRP level before ChRT (≥0.5 mg/dL) and their CSS rate was significantly worse than that in the remaining patients (P = 0.003). Multivariate analysis showed that CRP and cT stage were independent prognostic indicators for CSS, with a hazard ratio of 1.80 (95% confidence interval 1.01–2.97; P = 0.046). Among 10 patients in those with elevated CRP the CRP levels became normal after ChRT in six, of whom all but one was alive with no evidence of recurrence or metastasis during the follow‐up. By contrast, all four with no CRP normalization after ChRT died within 2 years.

CONCLUSIONS

To our knowledge this is the first study to report that elevation of CRP before treatment predicts a poor prognosis in patients with muscle‐invasive bladder cancer who are receiving ChRT. Furthermore, failure of CRP levels to normalize after ChRT was associated with extremely poor survival.     

Effects of perineural invasion on biochemical recurrence and prostate cancer-specific survival in patients treated with definitive external beam radiotherapy

Objectives

Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT).

Quality of life after external beam radiotherapy for localized prostate cancer: Comparison with other modalities

In external beam radiotherapy for localized prostate cancer, acute toxicities are typically transient and mild. These symptoms will disappear within 4–8 weeks after external beam radiotherapy. Some patients might suffer from proctitis with bloody stools as late rectal toxicity. Therefore, it has been shown that external beam radiotherapy has a more pronounced negative impact on bowel function compared with other treatment modalities. However, the recent development of modern beam delivery techniques, including intensity‐modulated radiotherapy, allows us not only to deliver higher doses to the prostate, but also to decrease the doses to the critical organs, resulting in the maintenance of patients’ quality of life within satisfactory levels. Patients’ quality of life after external beam radiotherapy is also strongly related to the total dose, fractionation regimens, dose parameters of the critical organs and treatment plan quality, with a trade‐off between the radicality of external beam radiotherapy and potentially increased toxicity. Radiation oncologists should choose treatment parameters carefully to achieve a reasonable balance between a good oncological outcome and the patient's quality of life.     

Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review

Context

Some studies report that tumour progression in patients with non-muscle-invasive bladder cancer (NMIBC) is associated with a poor prognosis. However, no systematic evidence is available.

Objective

The aim of the study was to systematically review literature to determine the long-term cancer-specific survival in patients with high-risk NMIBC (T1G3, multifocal, highly recurrent, or carcinoma in situ) having tumour progression.

Evidence acquisition

A systematic review was conducted by searching PubMed and the Cochrane library for studies published between 2006 and 2011. Additional studies were identified by scanning reference lists of relevant papers. We attempted to retrieve missing data by contacting the corresponding author. Keywords used included bladder cancer, high-risk, high grade, carcinoma in situ, non-muscle invasive bladder cancer, progression, and survival. Studies were included when they met the following criteria: inclusion of at least 75 patients having high-risk NMIBC, patients were initially treated conservatively with transurethral resection of the bladder tumour and intravesical instillations, a median follow-up of at least 48 mo, and reporting data on progression to muscle-invasive bladder cancer (MIBC) and death resulting from bladder cancer (BCa).

Evidence synthesis

Literature was systematically reviewed, and 19 trials were included, producing a total of 3088 patients, of which 659 (21%) showed progression to MIBC and 428 (14%) died as a result of BCa after a median follow-up of 48-123 mo. Survival after progression from high-risk NMIBC to MIBC was 35%. Progression to MIBC and BCa-related death in high-risk NMIBC were found to be relatively early events, occurring mainly within 48 mo. Finally, even in cases of early cystectomy in patients with high-risk NMIBC, a relevant proportion of these patients appear not be cured of their disease.

Conclusions

This study provides systematically gathered evidence showing a poor prognosis for patients with high-risk NMIBC and tumour progression.     

Combined external beam radiotherapy and Pd-103 brachytherapy boost improves biochemical failure free survival in patients with clinically localized prostate cancer: results of a matched pair analysis

BACKGROUND: Dose escalation has resulted in improved biochemical control in patients with clinically localized prostate cancer treated with conformal external beam radiation (EBRT). Conformal dose distributions may also be achieved with brachytherapy. Therefore, biochemical control was evaluated for patients treated with combined external radiation therapy and low dose rate brachytherapy (EBRT + LDR). METHODS: A matched pair analysis was performed to compare biochemical control of patients treated with EBRT + LDR to patients treated with EBRT alone. The study endpoints were biochemical control and late toxicities. RESULTS: The 5-year biochemical failure free survival (BFFS) was 86% for patients treated with EBRT + LDR and 72% for patients treated with EBRT (P = 0.03). Both treatments were associated with comparable incidences of late genitourinary (GU) side effects (18-19%). Late rectal toxicity was decreased by 15% in patients treated with EBRT + LDR (P = 0.0003). CONCLUSIONS: These results support EBRT followed by brachytherapy boost as a safe and effective method for dose escalation in the treatment of prostate cancer.     

Significance of preoperative butyrylcholinesterase as an independent predictor of survival in patients with muscle-invasive bladder cancer treated with radical cystectomy

ObjectivesButyrylcholinesterase (BChE) is an alpha-glycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, inflammation, injury, infection, malnutrition, and malignant disease. In this study, we analyzed the potential prognostic significance of preoperative BChE levels in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC).Methods and materialsWe retrospectively evaluated 327 patients with MIBC who underwent RC from 1996 to 2013 at a single institution. Serum BChE level was routinely measured before operation in all patients. Covariates included age, gender, preoperative laboratory data (anemia, BChE, lactate dehydrogenase, and C-reactive protein), clinical T (cT) and N stage (cN), tumor grade, and RC with/without neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall survival (OS) and disease-free survival (DFS). Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model.ResultsThe median BChE level was 187 U/l (normal range: 168–470 U/l). The median age of the enrolled patients was 69 years, and the median follow-up period was 51 months. The 5-year OS and DFS rates were 69.6% and 69.3%, respectively. The 5-year OS rates were 90.1% and 51.3% in the BChE≥168 and<168 U/l groups, respectively (P<0.001). The 5-year DFS rates were 83.5% and 55.4% in the BChE≥168 and≤167 U/l groups, respectively (P<0.001). In the univariate analysis, BChE, cT, cN, and RC with/without neoadjuvant chemotherapy were significantly associated with both OS and DFS. Multivariate analysis revealed that BChE was the factor most significantly associated with OS, and BChE, cT, and cN were significantly associated with DFS.ConclusionsThis study validated preoperative serum BChE levels as an independent prognostic factor for MIBC after RC.