Guidelines and recommendations

HEXVIX® is recommended…

A large body of high-quality clinical trial evidence demonstrates the clinical benefit of Hexvix® blue-light cystoscopy (BLC). Compared with white-light cystoscopy alone, Hexvix® BLC improves detection and resection of non-muscle-invasive bladder cancer, leading to reduced tumor recurrence. 16 As a result, Hexvix® is recommended by numerous expert groups and in international and national guidelines:

 

By European, US, and Nordic expert panels In European and international guidelines In national guidelines
    • EAU: European Association of Urology (2015) 3
    • ICUD: International Consultation on Urological Diseases (2012) 71
    • NCCN: National Comprehensive Cancer Network (2015) 72
    • NICE: National Institute for Health and Care Excellence (2015) 66
    • AUA: American Urological Association (2016) 90
  • Denmark: Dansk BlæreCancer Gruppe (2015) 74
  • France: Association Française d’Urologie (2013) 75
  • Italy: Associazione Italiana di Oncologia Medica (2014) 76
  • Norway: Nasjonalt handlingsprogram (2013) 77
  • Sweden: Nationelt vårdprogram (2015) 78

Click on the links for more details about these guidelines and recommendations

Expert Group Recommendations

European Expert Panel Recommendations, 2014

In 2014, a panel of European expert urologists provided advice on the optimal use of Hexvix® BLC, based on the latest evidence. Their aim was to encourage consistent use of Hexvix® as a standard of care across Europe. The European Expert Panel made the following recommendations: 67

Hexvix is recommended

BCG: bacillus Calmette–Guérin; BLC: blue-light cystoscopy; BLFC: blue-light flexible cystoscopy; NMIBC: non-muscle-invasive bladder cancer; TURB: transurethral resection of the bladder; WLC: white-light cystoscopy

The European consensus panel’s guidance was based on the proven clinical benefits of Hexvix® and the need to reduce the burden that this disease places on patients as well as healthcare services, because of the high risk of recurrence and potential for progression. The panel highlighted evidence that Hexvix® BLC is no more expensive than WLC alone and will result in improved quality-adjusted life years (QALYs) and reduced cost over time, based on two health-economic models: 67

  • UK analysis: 79
    • 0.060 QALYs gained
    • Cost savings of £391 per patient
  • Italian analysis: 80
    • 0.052 QALYs gained
    • Incremental cost-effectiveness ratio: €2,305 per QALY

See “Scientific information” section for further information

“We believe that short-term economic arguments about the initial costs of treatment should not prevail, and patients should not be denied access to HAL [Hexvix®] on the basis of the fact that the cost benefit would not be achieved immediately. Over the long term, there is a clear benefit with HAL‑guided BLC versus WLC, both for the health care system and, critically, for the patient.” 67

Patient selection

The European Expert Panel developed an algorithm identifying the points on the patient’s management pathway at which Hexvix® blue-light cystoscopy should be considered: 67


Adapted from Witjes JA et al., Clinical and Cost Effectiveness of Hexaminolevulinate-Guided Blue-Light Cystoscopy: Evidence Review and Updated Expert Recommendations; European Urology 2014; 66(5):863-871.

US Expert Panel Recommendations, 2014

Familiarity with blue-light cystoscopy (BLC) in the USA has been increasing since Cysview® (name of Hexvix® in the USA) was approved by the US Food and Drug Administration in 2010. In 2014, an expert panel of urologists, who had varying levels of familiarity with Hexvix®, discussed the evidence-based settings in which they would recommend Hexvix® BLC. The panel’s conclusions are summarised in the following table: 68

US expert panel reccs 2014 table

“Extensive evidence and clinical experience show that HAL [Hexvix®]–BLC can improve the detection of NMIBC beyond that achieved with WLC [white-light cystoscopy], which is the current standard of care. As a result, patients can benefit from a more complete TURBT [transurethral resection of bladder tumor] and more accurate staging, resulting in more appropriate management decisions, with reduced risk of recurrence and prolonged time to recurrence.” 68

 

Nordic Expert Panel Recommendations, 2012

In 2012, a Nordic Expert Panel reviewed recommendations on the use of Hexvix® blue-light cystoscopy (BLC) made by an earlier European Expert Panel (published in 2010) 4and considered whether and how those recommendations could be applied in Nordic countries. The Nordic Expert Panel’s modifications to the 2010 European recommendations are shown here: 5

Adapted from Malmström PU et al., Role of Hexaminolevulinate-Guided Fluorescence Cystoscopy in Bladder Cancer: Critical Analysis of the Latest Data and European Guidance; Scandinavian Journal of Urology and Nephrology 2012;46(2):108-116.

Patient selection

The Nordic panel published a useful algorithm for use of Hexvix® BLC: 5

Patient selection table

Adapted from Malmström PU et al., Role of Hexaminolevulinate-Guided Fluorescence Cystoscopy in Bladder Cancer: Critical Analysis of the Latest Data and European Guidance; Scandinavian Journal of Urology and Nephrology 2012;46(2):108-116.


European and International Guidelines

EAU Guidelines 20153

“The goal of TURB [transurethral resection of the bladder] in Ta, T1 BC [bladder cancer] is to make the correct diagnosis and remove all visible lesions.”

“Complete and correct TURB is essential to achieve a good prognosis” 

EAU guidelines confirm the clinical evidence that biopsy and resection with blue-light cystoscopy (BLC) are more sensitive than conventional white-light cystoscopy (WLC) for detection of malignant tumors, particularly carcinoma in situ (CIS; LE 2a*)

Hexvix® is recommended… 3

Instead of random biopsies when bladder CIS or high-grade tumor is suspected (e.g., positive urine cytology or recurrence following a previous high-grade lesion) (GR B)

The EAU 2015 guidelines are based on meta-analyses, which show:

  • Higher sensitivity with BLC than with WLC at both the patient level (92% vs 71%) and the biopsy level (93% vs 65%)82
    • False-positivity can be induced by inflammation or recent resection and during the first 3 months after BCG instillation (LE 3) 83
  • Increase in lesion detection across all risk groups and a reduction in recurrence rates with Hexvix® BLC vs WLC in the 12 months following initial resection (LE 1a*) 16

ICUD Guidelines 2012

Hexvix® is recommended… 71

ICUD-Recs v2

“Non-muscle-invasive bladder cancer is associated with a significant risk of recurrence; thus, lifelong patient surveillance is required. PDD [photodynamic diagnosis; another term for blue-light cystoscopy] can improve detection of disease, especially CIS [carcinoma in situ]; improve completeness of resection; and, most importantly, reduce rates of recurrence of non-muscle invasive bladder cancer. Improved initial resection, such as with PDD, has been suggested to improve recurrence rates after intravesical chemotherapy, but this needs to be further evaluated in clinical trials.” 71

NCCN Guidelines 2015

Hexvix® is recommended… 72
In patients with

  • Papillary-appearing tumor (likely non-muscle-invasive)
  • Suspected or known carcinoma in situ (CIS)

The NCCN guidelines conclude that blue-light cystoscopy (BLC) may have the greatest advantage in detecting difficult-to-visualize tumors (e.g., CIS) that may be missed by white-light cystoscopy (WLC), 72 on the basis of data from two meta-analyses showing: 16,84

  • Significantly improved detection of primary and recurrent tumors with BLC vs WLC
  • Detection of ≥1 lesion by BLC but not WLC in ≥25% of patients
  • Significantly reduced tumor recurrence rate with BLC vs WLC
  • Improved recurrence-free survival at 1 and 2 years with BLC vs WLC

See “Scientific information” section for further information

“Blue light cystoscopy may be helpful in identifying lesions not visible using white light cystoscopy” 72

 

NICE Guidelines 2015

Hexvix® is recommended… 66

  • For patients with suspected bladder cancer

NICE recommends the use of technologies such as blue-light cystoscopy (BLC) to improve diagnostic accuracy, which can in turn lead to fewer tumor recurrences and therefore fewer resections, compared with white-light cystoscopy (WLC) alone. Although BLC may result in unnecessary biopsies due to false-positive findings, improved sensitivity is considered more important for patients. 66

The NICE guidelines indicate that this approach could be cost effective compared with current practice, despite the costs associated with BLC and increased biopsies, because of the potential savings from more accurate diagnosis and the reduction in residual disease and recurrence risk. 66

“Of particular note to the topic at hand is that photodynamic diagnosis (PDD) [another term for blue‑light cystoscopy] appears to be a cost‑effective alternative to WLC as an initial diagnostic test.” 66

 

AUA Guidelines 201690

A complete TURBT is critical in management of NMIBC for accurate tumor type, staging, grading, and optimization of patient outcomes.

Enhanced Cystoscopy In a patient with NMIBC, a clinician should offer blue light cystoscopy (BLC) at the time of TURBT, if available, to increase detection and decrease recurrence. (Moderate Recommendation; Evidence Strength: Grade B)

Diagnosis In a patient with a history of NMIBC with normal cystoscopy and positive cytology, a clinician should consider prostatic urethral biopsies and upper tract imaging, as well as enhanced cystoscopic techniques (blue light cystoscopy, when available), ureteroscopy, or random bladder biopsies (Expert Opinion). Enhanced cystoscopy and newer resection techniques, such as bipolar electrocautery, may serve to enhance complete resection and reduce complications from TURBT.

European Country-specific Guidelines




References: Denmark74, France75, Italy76, Norway77, Sweden78
*Levels of evidence:
LE 1a: evidence obtained from meta-analysis of randomized trials
LE 2a: evidence obtained from one well designed controlled study without randomization
LE 3: evidence obtained from well designed non-experimental studies, such as comparative studies, correlation studies, and case reports
Grade of recommendation:
GR B: recommendation based on well conducted clinical studies, but without randomized clinical trials