Background.
Platinum‐based neoadjuvant chemotherapy has been shown to improve survival outcomes in muscle‐invasive bladder cancer patients. We performed a systematic review and meta‐analysis to ...provide updated results of previous findings. We also summarized published data to compare clinical outcomes of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) versus gemcitabine and cisplatin/carboplatin (GC) in the neoadjuvant setting.
Methods.
A meta‐analysis of 15 randomized clinical trials was performed to compare neoadjuvant chemotherapy plus local treatment with the same local treatment alone. Because no randomized trials have investigated MVAC versus GC in the neoadjuvant setting, a meta‐analysis of 13 retrospective studies was performed to compare MVAC with GC.
Results.
A total of 3,285 patients were included in 15 randomized clinical trials. There was a significant overall survival (OS) benefit associated with cisplatin‐based neoadjuvant chemotherapy (hazard ratio HR, 0.87; 95% confidence interval CI, 0.79–0.96). A total of 1,766 patients were included in 13 retrospective studies. There was no significant difference in pathological complete response between MVAC and GC. However, GC was associated with a significantly reduced overall survival (HR, 1.26; 95% CI, 1.01–1.57). After excluding carboplatin data, GC still seemed to be inferior to MVAC in OS (HR, 1.31; 95% CI, 0.99–1.74), but the difference was no longer statistically significant.
Conclusion.
These results support the use of cisplatin‐based combination neoadjuvant chemotherapy in muscle‐invasive bladder cancer. Although GC and MVAC had similar treatment response rates, the different survival outcome observed in this study requires further investigation.
Implications for Practice:
Platinum‐based neoadjuvant chemotherapy (NCT) has been shown to improve survival outcomes in muscle‐invasive bladder cancer (MIBC) patients, but the optimal neoadjuvant regimen has not been established. Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin/carboplatin (GC) are two of the most commonly used chemotherapy regimens in modern oncology. In this two‐step meta‐analysis, an updated and more precise estimate of the survival benefit of cisplatin‐based NCT in MIBC is provided. This study also demonstrated that MVAC might have superior overall survival compared with GC (with or without carboplatin data) in the neoadjuvant setting. The findings suggest that NCT should be standard care in MIBC, and MVAC could be the preferred neoadjuvant regimen.
This systematic review and two‐step meta‐analysis examined existing literature to assess neoadjuvant chemotherapy (NCT) for muscle‐invasive bladder cancer (MIBC). Findings support the use of cisplatin‐based combination NCT to treat MIBC, but further investigation is warranted.
The role of surgery in metastatic bladder cancer (BCa) is unclear.
In this collaborative review article, we reviewed the contemporary literature on the surgical management of metastatic BCa and ...factors associated with outcomes to support the development of clinical guidelines as well as informed clinical decision-making.
A systematic search of English language literature using PubMed-Medline and Scopus from 1999 to 2016 was performed.
The beneficial role of consolidation surgery in metastatic BCa is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy (CHT). Intraoperatively identified enlarged pelvic lymph nodes should be removed. Anecdotal reports of resection of pulmonary metastasis as part of multimodal approach suggest possible improved survival in well-selected patients. Cytoreductive radical cystectomy as local treatment has also been explored in patients with metastatic disease, although its benefits remain to be assessed.
Consolidative extirpative surgery may be considered in patients with clinically evident pelvic or retroperitoneal lymph nodal metastases but only if they have had a response to CHT. Surgery for limited pulmonary metastases may also be considered in very selected cases. Best candidates are those with resectable disease who demonstrate measurable response to CHT with good performance status. In the absence of data from prospective randomized studies, each patient should be evaluated on an individual basis and decisions made together with the patient and multidisciplinary teams.
Surgical resection of metastases is technically feasible and can be safely performed. It may help improve cancer control and eventually survival in very selected patients with limited metastatic burden. In a patient who is motivated to receive chemotherapy and to undergo extirpative surgical intervention, surgery should be discussed with the patient among other consolidation therapies in the setting of multidisciplinary teams.
A multimodal approach that includes radical cystectomy and lymphadenectomy seems to improve cancer control and survival in bladder cancer patients with nodal metastasis. Metastasectomy is feasible and can be safely performed with a possible survival advantage in well-selected patients.
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Purpose We assessed the impact of primary surgery, including penile sparing surgery vs (partial) penectomy and lymphadenectomy, on sexuality and health related quality of life. Materials and Methods ...We invited 147 patients surgically treated for penile cancer at our institution between 2003 and 2008 to complete the IIEF-15, SF-36®, IOC (version 2) and questions on urinary function. We evaluated the impact of primary surgery type and lymphadenectomy on these outcomes. We also compared patient SF-36 scores with those of an age and gender matched normative sample from the general Dutch population. Results A total of 90 patients (62%) returned a completed questionnaire. Surgery type and extent were not associated significantly with most of the study outcomes assessed. However, men who underwent (partial) penectomy reported significantly more problems than those treated with penile sparing surgery, including orgasm (effect size 0.54, p = 0.031), appearance concerns (effect size 0.61, p = 0.008), life interference (effect size 0.49, p = 0.032) and urinary function (83% vs 43%, p <0.0001). Men who underwent lymphadenectomy reported significantly more life interference (effect size 0.50, p = 0.037). The patient sample scored significantly better than the normative sample on the SF-36 physical component (p = 0.044) and the bodily pain subscale (p <0.001). Conclusions Few differences were observed in sexuality and health related quality of life as a function of primary surgery and lymphadenectomy. However, (partial) penectomy and lymphadenectomy were associated with more problems with orgasm, body image, life interference and urination. Additional longitudinal studies are warranted to evaluate individual changes with time in these outcomes.
Purpose Sentinel lymph node biopsy is emerging as a promising method for inguinal lymph node staging of penile squamous cell carcinoma. In the current systematic review we evaluated the accuracy of ...sentinel lymph node biopsy for inguinal lymph node staging of penile squamous cell carcinoma and studied possible influential factors. Materials and Methods MEDLINE®, Scopus®, ISI®, Ovid SP®, Springer, ScienceDirect® and Google™ Scholar were searched by the key words “(penile OR penis) AND sentinel”. No date or language limitation was imposed on the search and meeting abstracts were not excluded from analysis. A random effects model was used for statistical pooling. Results A total of 17 studies suitable for meta-analysis were detected. Three articles had 2 different subgroups of patients and each subgroup was considered as a separate study. Overall 18 studies (including the subgroups) were used for detection rate meta-analysis and 19 for sensitivity meta-analysis. The pooled detection rate was 88.3% (95% CI 81.9–92.6). Pooled detection rate of 90.1% (95% CI 83.6–94.1) was calculated for the studies using blue dye and radiotracer. The pooled sensitivity was 88% (95% CI 83–92). The highest pooled sensitivity (92% 95% CI 86–96) was in the studies using radiotracer and blue dye, and recruiting only cN0 cases. Conclusions Sentinel lymph node mapping in penile squamous cell carcinoma is a method with a high detection rate and sensitivity. Using radiotracer and blue dye for sentinel lymph node mapping and including only cN0 disease ensures the highest detection rate and sensitivity.
The host's immune system plays a pivotal role in many tumor types, including squamous cell carcinomas (SCCs). We aim to identify immunological prognosticators for lymph node metastases (LNM) and ...disease-specific survival (DSS) in penile SCC. For this retrospective observational cohort study, penile SCC patients (
= 213) treated in the Netherlands Cancer Institute, were selected if sufficient formalin-fixed, paraffin-embedded tumor material was available. Analysis included previously described high-risk human papilloma virus (hrHPV) status, immunohistochemical scores for classical and non-classical human leukocyte antigen (HLA) class I, programmed death ligand-1 (PD-L1) expression, and novel data on tumor-infiltrating macrophages and cytotoxic an regulatory T-cells. Clinicopathological characteristics and extended follow-up were also included. Regression analyses investigated relationships of the immune parameters with LNM and DSS. In the total cohort, diffuse PD-L1 tumor-cell expression, CD163
macrophage infiltration, non-classical HLA class I upregulation, and low stromal CD8
T-cell infiltration were all associated with LNM. In the multivariable model, only tumor PD-L1 expression remained a significant predictor for LNM (odds ratio (OR) 2.8,
= 0.05). hrHPV negativity and diffuse PD-L1 tumor-cell expression were significantly associated with poor DSS and remained so upon correction for clinical parameters hazard ratio (HR) 9.7,
< 0.01 and HR 2.8,
= 0.03. The only immune factor with different expression in HPV
and HPV
tumors was PD-L1, with higher PD-L1 expression in the latter (
= 0.03). In the HPV
cohort (
= 158), LNM were associated with diffuse PD-L1 tumor-cell expression, high intratumoral CD163
macrophage infiltration, and low number of stromal CD8
T-cells. The first two parameters were also linked to DSS. In the multivariable regression model, diffuse PD-L1 expression remained significantly unfavorable for DSS (HR 5.0,
< 0.01). These results emphasize the complexity of the tumor microenvironment in penile cancer and point toward several possible immunotherapy targets. Here described immune factors can aid risk-stratification and should be evaluated in clinical immunotherapy studies to ultimately lead to patient tailored treatment.
Abstract Context Uncertainty remains about the extent and indications for inguinal lymphadenectomy in penile cancer, a procedure known for relatively high morbidity. Several attempts have been made ...to develop strategies which can improve the diagnostic quality and reduce the morbidity of the management of inguinal lymph nodes in penile cancer. Objective To analyse the existing published data on the surgical management of inguinal nodes in penile cancer regarding morbidity and survival. Evidence acquisition A Medline search was performed of the English-language literature (1966–September 2008) using the MeSH terms penile carcinoma , lymph node dissection , lymphadenectomy , and complications. Evidence synthesis Lymph node metastases are frequent in penile cancer, even in early pT1G2 stages. Since the results of systemic treatment of advanced penile cancer are disappointing, complete dissection of all involved lymph nodes is highly recommended. The extent of lymph node dissection should be adapted to clinical stage, as this corresponds to metastatic spread. For low-risk patients (pTis, pTa, and pT1G1) without palpable lymph nodes and with good compliance, a surveillance strategy may be chosen. For all other patients without palpable lymph nodes (including intermediate risk pT1G2 disease), a modified bilateral lymphadenectomy is recommended. An alternative to this is a dynamic sentinel lymph node biopsy in specialised centres. All patients with histologically proven lymph node metastases should undergo radical inguinal lymphadenectomy. Pelvic lymph node dissection should be done in all patients with more than two metastatic inguinal lymph nodes. In case of fixed inguinal lymph nodes, neoadjuvant chemotherapy is recommended, followed by node resection. Conclusions Lymphadenectomy is an integral part of the management of penile cancer, since early dissection of involved lymph nodes improves survival.
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Arterio-ureteral fistula (AUF) is an uncommon diagnosis, but increasingly reported and potentially lethal. This systematic review comprehensively presents risk factors, pathophysiology, location and ...clinical presentation of AUF aiming to increase clinical awareness of this rare but life-threatening condition, and to put this entity into a contemporary perspective with modern diagnostic tools and treatment strategies.
This review was performed according to the PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis of Individual Participant Data) guidelines. A literature search in PubMed® and EMBASE™ was conducted. In addition, retrieved articles were cross-referenced. Data parameters included oncologic, vascular and urological history, diagnostics, treatment, and followup, and were collected using a standard template by 2 independent reviewers.
A total of 245 articles with 445 patients and 470 AUFs were included. Most patients had chronic indwelling ureteral stents (80%) and history of pelvic oncology (70%). Hematuria was observed in 99% of the patients, of whom 76% presented with massive hematuria with or without previous episodes of (micro)hematuria. For diagnosis, angiography had a sensitivity of 62%. The most predominant location of AUF was at the common iliac artery ureteral crossing. AUF-specific mortality before 2000 vs after 2000 is 19% vs 7%, coinciding with increasing use of endovascular stents.
AUF should be considered in patients with a medical history of vascular surgery, pelvic oncologic surgery, irradiation and/or chronic indwelling ureteral stents presenting with intermittent (micro)hematuria. A multidisciplinary consultation is necessary for diagnosis and treatment. The most sensitive test is angiography and the preferred initial treatment is endovascular.
To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors.
In our nationwide ...cohort comprising 2,707 5-year TC survivors, incidences of SMNs and CVDs were compared with general-population rates by calculating standardized incidence ratios (SIRs) and absolute excess risks (AERs). Treatment effects on risks of SMN and CVD were quantified in multivariable Cox regression and competing risks analyses.
After a median follow-up time of 17.6 years, 270 TC survivors developed SMNs. The SIR of SMN overall was 1.7 (95% CI, 1.5 to 1.9), with an AER of 32.3 excess occurrences per 10,000 person-years. SMN risk was 2.6-fold (95% CI, 1.7- to 4.0-fold) increased after subdiaphragmatic radiotherapy and 2.1-fold (95% CI, 1.4- to 3.1-fold) increased after chemotherapy, compared with surgery only. Subdiaphragmatic radiotherapy increased the risk of a major late complication (SMN or CVD) 1.8-fold (95% CI, 1.3- to 2.4-fold), chemotherapy increased the risk of a major late complication 1.9-fold (95% CI, 1.4- to 2.5-fold), and smoking increased the risk of a major late complication 1.7-fold (95% CI, 1.4- to 2.1-fold), compared with surgery only. The median survival time was 1.4 years after SMN and 4.7 years after CVD.
Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.
Abstract Background Sentinel node (SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye. Recently, the hybrid radioactive and fluorescent tracer ...indocyanine green (ICG)-99m Tc-nanocolloid was developed to combine the beneficial properties of both radio-guidance and fluorescence imaging. Objective To explore the added value of SN biopsy using ICG-99m Tc-nanocolloid in patients with penile carcinoma. Design, setting, and participants Sixty-five patients with penile squamous cell carcinoma were prospectively included (January 2011 to December 2012). Preoperative SN mapping was performed using lymphoscintigraphy and single-proton emission computed tomography supplemented with computed tomography (SPECT/CT) after peritumoural injection of ICG-99m Tc-nanocolloid. During surgery, SNs were initially approached using a gamma probe, followed by patent blue dye and/or fluorescence imaging. A portable gamma camera was used to confirm excision of all SNs. Surgical procedure Patients underwent SN biopsy of the cN0 groin and treatment of the primary tumour. Outcome measurements and statistical analysis The number and location of preoperatively identified SNs were documented. Intraoperative SN identification rates using radio- and/or fluorescence guidance were assessed and compared with blue dye. Statistical evaluation was performed using a two-sample test for equality of proportions with continuity correction. Results and limitations Preoperative imaging after injection of ICG-99m Tc-nanocolloid enabled SN identification in all patients (a total of 183 SNs dispersed over 119 groins). Intraoperatively, all SNs identified by preoperative SN mapping were localised using combined radio-, fluorescence-, and blue dye guidance. Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was stained by blue dye ( p < 0.0001). The tissue penetration of the fluorescent signal, and the rapid flow of blue dye limited the detection sensitivity. A tumour-positive SN was found in seven patients. Conclusions ICG-99m Tc-nanocolloid allows for both preoperative SN mapping and combined radio- and fluorescence-guided SN biopsy in penile carcinoma patients and significantly improves optical SN detection compared with blue dye.
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Abstract Purpose We present a single institute experience of the four most widely used diversions after cystectomy in 281 patients, with an evaluation of the association between clinical factors, ...complication rates, functional results, and metabolic complications. Materials and methods Between 1990 and 2005, 281 consecutive cystectomies were performed at our institute. Four different diversions were offered: an ileal conduit according to Bricker (IC; 118 patients), an Indiana pouch (IP; 51 patients), and orthotopic diversions after cystectomy/neobladder (N; 62 patients), or sexuality-preserving cystectomy and neobladder (SPCN; 50 patients). Results Forty-four percent developed early complications: IC 48%, IP 43%, N 42%, and SPCN 38%. High ASA score was the only variable significantly associated with early major complications (ASA 1 vs. 3: HR, 0.32; 95%CI, 0.14–0.72). Late complication rate was 51% with fewer complications in the IC group, IC 39%, IP 63%, N 59%, and SPCN 60% (HR, 0.32; 95%CI, 0.14–0.72), which was explained by fewer uncomplicated urinary tract infections (one third of all late complications) in the IC group. There were no differences in experienced late major complications. We found no significant association between tumour stage, ASA, age, preoperative radiotherapy, gender, and diversion-related complication rates. Complete daytime and nighttime continence, respectively, was achieved in 96% and 73% after IP, 90% and 67% after neobladder, and 96% and 67% after SPCN. Metabolic changes were found in 24% of the patients: 21% after IC, 26% after IP, and 28% after orthotopic diversion (neobladder and SPCN combined); low vitamin B12 was measured in 23%, 15%, and 15% respectively. Conclusions Cystectomy with any subsequent diversion remains a procedure with considerable morbidity. High ASA score was associated with more early complications. Orthotopic diversions provide good functional results, but at the cost of more late complications compared with ileal conduits. We found no evidence that age, ASA score, positive lymph nodes, extravesical tumour growth, or previous radiotherapy were contraindications per se for any diversion.
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