Synergo in a rare case of T1 bladder cancer

Synergo® in a rare case of T1 bladder cancer

Bladder cancer is a rare phenomenon in children, with an incidence rate of 0.1-0.4% during the first two decades of their lives.

A recent new article (2022) published in the Journal of Pediatric Urology by Dr. Galia Raisin and Prof. Boris Chartin from Shaare Zedek Medical Center (Jerusalem) summarizes their experience and treatment outcomes in nine children, seven of whom are male (78%).

A single case of high-grade disease (UC pT1) was diagnosed in a 14-year-old girl, a kidney transplant recipient. Due to her immune status, she was ineligible for BCG treatment and therefore received 6 Synergo sessions, with no recurrence to date - at a follow-up of 4 years.

Galiya R, Stanislav K, Jawdat J, Benjamin H, Boris C. Pediatric urothelial bladder neoplasm. J Pediatr Urol. 2022 Jun 30:S1477-5131(22)00293-5. doi: 10.1016/j.jpurol.2022.06.026. Epub ahead of print. PMID: 35871900.

Synergo RF-CHT is effective in non-muscle invasive bladder cancer patients in whom standard intravesical treatments have failed and should be considered in patients who are unwilling or unfit to undergo radical cystectomy.

Long-Term Experience with Radiofrequency-Induced Hyperthermia Combined with Intravesical Chemotherapy for Non-Muscle Invasive Bladder Cancer.

We are honoured to share a peer-reviewed article on Synergo published in Cancers 2021 Journal by Iris S. G. Brummelhuis et al. https://pubmed.ncbi.nlm.nih.gov/33498535/. 

Their work concludes that Synergo is effective in NMIBC patients in whom standard intravesical treatments have failed and should be considered in patients who are unwilling or unfit to undergo radical cystectomy.

Patients characteristics:

299 intensively pretreated patients. Of these, 274 patients who fulfilled induction treatments were included in efficacy analysis. 

BCG-unresponsive NMIBC: 85.4% of the patients (BCG Refractory: 65% and BCG Intolerant 7.7%).

Patients with CIS with or without concomitant papillary tumor: 46.7% of the patients.

Results following Synergo treatment:

For CIS, six-month complete response -rate was 56.0%; and durable response rates were 79.7%, 66.5%, and 40.3% at one-, two- and five-year, respectively. 

Recurrence free survival rates for papillary patients were 77.9%, 57.5%, and 37.2%, at one-, two- and five-year, respectively respectively. 

Patients treated with ablative dose are less likely to develop recurrence (adjusted Hazard Ratio 0.54, p = 0.01), compared to adjuvant dose.

In total, 22 (8.5%) of all patients progressed to MIBC, of whom 20 had a high-grade tumor prior to RF-CHT and all 22 patients previously have been treated with BCG (21 BCG refractory, 1 unknown reason for BCG discontinuation). Eleven (4.3%) patients had distant metastases up to one year after treatment.

During the mean follow-up period of 55.5 months, 80 patients (29.2%) received a radical cystectomy with or without neoadjuvant chemotherapy. The bladder preservation rate for this follow-up period was thus 70.8%.

Medical Enterprises

Microwave-Induced Hyperthermia in combination with Chemotherapy: A retrospective analysis from Harlaching Hospital (2009-2015) Germany

We wish to congratulate Dr. Miriam Heibeler - with Head of department Prof. Dr. Oliver Reich at Klinikums Harlaching Lehrkrankenhaus der Ludwig-Maximilians-Universität München for her comprehensive thesis work on Synergo® published in 2020. We are extremely proud to share data from her study (translated from German). Full text: https://edoc.ub.uni-muenchen.de/25860/1/Hiebeler_Miriam.pdf

The following is a summary translated from Dr. Hiebeler study and with her permission.

The intended information is for professionals only.

Microwave-Induced Hyperthermia in combination 

with Chemotherapy: 

A retrospective analysis from Harlaching Hospital (2009-2015) 

Munich, Germany

Dr. Miriam Hiebeler

A total of 44 non-muscle invasive bladder cancer patients were treated with Synergo® in München Harlaching Hospital Munich between 2009-2015. 41% of the patients were treated according to the prophylactic (adjuvant) protocol and 59% treated according to Synergo® ablative (neo-adjuvant) protocol.

Synergo prophylactic (adjuvant):

18/44 (41%) intermediate and high-risk patients, of which 50% had history of recurring disease with an average of 2.3 incidences prior to Synergo therapy.

Results: At the end of Synergo® treatment cycle, all patients but 2 (11%), who were lost to follow-up, were tumor-free. 

14 of the 16 patients were tumor-free after completion of the Synergo therapy. This corresponds to 87.5% of the patients. The 2 patients who had a recurrence (mean time 2.3 years) both had pTaG1 tumor prior to Synergo which presented itself also when recurrence was recorded. 

The follow-up period for this cohort lasted an average of 3.2 years. 

No cystectomy had to be performed during that period. 

Synergo ablative (neo-adjuvant):

26/44 (59%) of the patients were treated. 90% were classified as high-risk (according to the EAU guidelines), with TaG3, T1G2, T1G3 and/or CIS. 73% of the patients thad history of recurring disease. 

An analysis of two groups who received Synergo ablative was performed. One group (62%) treated according to the protocol and the other (38%) was given Synergo as a therapy attempt although patients had contraindications prior to treatment (e.g. history of other tumours or urothelial carcinoma of the upper urinary tract). 

The Kaplan-Meier curve of all patients treated according to the ablative protocol shows 83% disease-free at one year and 70% at disease-free 5 years.

Below are the two ablative cohorts analysed separately:

Results of ablative Synergo:

16 patients were treated according to the Synergo recommended protocol. 15/16 of the patients were classified high-risk (according to EAU), one patient was classified as intermediate-risk. 73% of the patients had a history of disease and several were highly recurrent (3 or more episodes in the previous two years). 6 patients were “first episode” who had been diagnosed with T1 or high-grade carcinoma. Five of the latter had concomitant carcinoma in situ (CIS).

Of the 16 patients treated, 15 (93.8%) patients showed a complete response rate (tumor-free urinary bladder biopsies at the end of the ablation series). The average time to complete response was 1.9 months.

In one patient, the ablation therapy had no effect and a progression from TaG3 to pT2aG2 was recorded. This patient was cystectomised. Patients with complete response continued treatment and follow-up. The mean follow-up time was 24.2 months.

13/15 (86.7%) of the patients remained disease free for an average of 26 months and showed no further tumor formation during this period. Two patients (13.3%) had tumor recurrence. They were ultimately cystectomised after a follow-up period of 24.2 months.

In total, four of the 16 patients had to have their bladder removed. Two patients suffered tumor recurrence, one patient showed tumor progression and a cystectomy was performed on another patient with a reduced bladder capacity of less than 90 ml. The resected bladder, however, was completely tumor-free. One patient was partially resected because of a suspected tumor recurrence. The resected material was tumor-free. In the subsequent examinations, no new tumor was detected in the rest of the urinary bladder.

Results of ablative Synergo in patients with known exclusion criteria for Synergo 10/26):

One patient stopped therapy prematurely due to severe allergic skin reactions. His therapy results were not taken into account.

7/9 (77.8%) showed no tumor recurrence or progression after a follow-up period of an average of 33.4 months.

Two patients (22.2%) experienced recurrence in the form of muscle-invasive carcinoma. One developed pT2G3 carcinoma from TaG3 stage, the other developed invasive pT3aG3 carcinoma from T1G3 tumor. This patient (11.1%) underwent a cystectomy ten months after start of Synergo therapy.

A total of three patients (33.3%) died as a result of bladder carcinoma. In two patients the urinary bladder was tumor-free at the time of death; they died from extensive metastasis. The average time to death was 14.3 Months.

Side effects to therapy:

Side effects noted in a total of 63% of the prophylactic treated patients and in 69% of the ablative treated patients.

The most common were pain in the form of bladder cramps during treatments, dysuria, nocturia and allergy. Severe complications in the form of urethral strictures occurred in 27.8% of the patients, although there was no stricture impeding a cystoscope to pass. The most noted side effect observed in almost all patients during cystoscopy was posterior thermal wall reaction (average grade 2 in both groups). The posterior thermal wall reaction is symptom-free and disappears after a few months. Below are the detailed tables of side effects recorded in both prophylactic and ablative Synergo treatments.

Medical Disclaimer

While clinical studies support the safety and effectiveness of the Synergo® RF thermo-chemotherapy system when used in the treatment of non-muscle invasive bladder cancer, results may vary. There are no guarantees of outcome. Before you decide on treatment options, discuss them with your doctor. Understanding the risks of each treatment can help you make the best decision for your individual situation. Synergo treatment may not be appropriate for every individual; it may not be applicable to your condition. Always ask your doctor about all treatment options, as well as their risks and benefits. Only your doctor can determine whether Synergo is appropriate for your situation. 

Synergo for High-risk NMIBC

Urology Cancer specialists,

We are proud and honoured to share an article published in October 2020, by Denosshan Sri et al. St Georges Urology Centre (London) on Urologic Oncology. 

https://doi.org/10.1016/j.urolonc.2020.09.016

Cystectomy outcomes in patients who have failed Radiofrequency-induced Thermo-chemotherapeutic Effect Mitomycin-C (RITE-MMC) treatment for high-risk non-muscle invasive bladder cancer (HRNMIBC) -Does it complicate surgery and adversely impact oncological outcome?

Denosshan Sri, Hack Jae Lee, Sarah El-Gemmal, Chris Backhouse, Andrea Tay, Babbin John, Matthew J Perry, Benjamin E Ayres, Rami Issa St. George's Hospital, London, UK

Highlights for Review

Radiofrequency-Induced Thermo-chemotherapeutic Effect Mitomycin (RITE-MMC) can be an alternative in BCG failure.

RITE-MMC treatment does not result in a technically more challenging cystectomy.

RITE-MMC treatment does not compromise oncological outcome compared to those patients undergoing cystectomy immediately post BCG failure.

The article presents a retrospective study of a prospective cystectomy database. Inclusion criteria were HRNMIBC with BCG failure undergoing cystectomy.

Thirty-six patients who received RITE-MMC underwent cystectomy, compared to 102 that did not. Median ages were comparable at 72 and 69 years, respectively. Patients were followed up for a median of 24 months across the 2 groups. The commonest histological stage in both groups was CIS. There were no significant differences in intraoperative blood loss, length of stay and 90-day readmission between the 2 groups. There were proportionally fewer recurrences in the RITE-MMC group (16% vs. 19%) and median time to recurrence was longer in the RITE-MMC group (37 months vs. 24 months). Multivariate analysis did not reveal a significant correlation between pre-op RITE-MMC and post-operative readmission (P = 0.606). Survival curves show no significant difference in time to recurrence across both groups (P = 0.513), and no overall (P = 0.069) or cancer specific mortality (P = 0.129) dis-advantage was noted in the RITE-MMC group.

Conclusion
We have found that RITE-MMC treatment does not result in a technically more challenging cystectomy and does not compromise oncological outcome compared to those patients undergoing cystectomy immediately post-BCG failure. We feel RITE-MMC remains a useful tool in a carefully selected group of patients who may not be willing to accept the morbidity of a cystectomy at the time, without significantly compromising their long-term outcome.

 

Medical Enterprises’s commentary:

St Georges University Hospital Urological centre is one of the leading Referral Centres of Synergo worldwide and its dedicated team accumulated a vast experience over the past 16 years with Synergo Radiofrequency-Induced ThermoChemotherapy (RITE).

One may note that, as such, the referrals to the hospital for cystectomy constitutes a very high number, and seeing the relatively few cystectomies carried out on patients whom previously received radiofrequency treatment in the bladder prompts hope for many patients who opt to preserve their bladders despite the indication for a radical surgery.

This researcher’s group has presented their bladder preservation study in over 10 years follow-up (Link to the study), and this new article sheds light on the possibility of administering RITE as a last step before radical cystectomy (as recurrence and progression rates are oncologically similar), while in the relatively low percentage of patients who would fail this modality over time, a surgery would not impose a greater risk of complications than in an early cystectomy.

A history note: 1995 post R&D

25 years ago!

Synergo at the very outset. The year is 1995. A group of urologists and scientists at HSR publishes its first article and presents a new device based on a microwave source delivering local bladder hyperthermia together with intravesical chemotherapy.



44 patients treated. Overall response rate in 90.8%: 70.4% complete and 20.4% partial.

Positive, repetitive results have led to the development of the “Synergo®”.

Synergo® RITE technology was specifically developed and designed to deliver local microwave hyperthermia (radiofrequency) in combination with chemo to treat Non Muscle invasive Bladder Cancer. All administered via Synergo transurethral RF applicator.

Starting as early as 1992 and continuously to date clinical trials have been conducted to study the benefits of combined treatment of Synergo® over chemotherapy and immunotherapy alone for people who suffer from NMIBC and other tumors in the bladder. The treatment has become a common practice in leading centres both as a prophylactic treatment (after TUR) and ablative treatment (for tumour eradication).

Photo below: pre-Synergo: transurethral microwave bladder with chemo instillation. A lamp was used to hold the embedded antenna within the silicone catheter.

Photo: 25 years ago! Synergo at the very outset. A designed device. Arm replaces the lamp. 

"Tough times never last, but tough people do."—Robert H. Schuller

Together, we are facing a truly unprecedented situation. The global coronavirus pandemic is affecting all of our families, our businesses, our communities, and our way of life.
We are truly inspired by the selfless healthcare workers around the world who are on the front lines working tirelessly to care for people in need.

We wish you and your families stay safe & healthy, gradual and phased return, as we continue to work together as a collective community to support business continuity and each other.

Sincerely, 

Medical Enterprises Team

Updates from the European Association of Urology Guidelines 2017

Bladder Cancer - Updates from the European Association of Urology Guidelines:

Background:

The Synergo® treatment has become a common practice in leading centers both as a prophylactic treatment (after TUR) and ablative treatment (for tumour eradication). The prophylactic induction phase includes 6 weekly sessions followed by 6 in a maintenance phase, once every 6 weeks. The clinical outcomes of this adjuvant protocol were recently included in the European Association of Urology Guidelines. A multinational randomised controlled trial comparing the efficacy and safety of Synergo® vs. BCG, presents better results in the Synergo® group (Disease free patients: 81.8% vs. 64.8% respectively in 2-yr follow-up). 

With the new recommendations, Synergo®’s level of evidence makes it the only non-experimental device for the treatment of NMIBC.

The following is taken from the EAU 2017 guidelines:

EAU Guidelines. Edn. presented at the EAU Annual Congress London 2017. ISBN 978-90-79754-91-5.

 

7.3.3.Treatment of BCG failure and recurrences after BCG

Treatment recommendations are provided in Sections 7.5 and 7.7. They reflect the categories mentioned in Table 7.2 and tumour characteristics at the time of recurrence.

Patients with BCG failure are unlikely to respond to further BCG therapy; RC is therefore the preferred option. Various studies suggest that repeat BCG therapy is appropriate for non-high-grade and even for some high-grade recurrent tumours [232,233] (LE: 3). Additionally, there are now several bladder preservation strategies available that can be categorised as intravesical immunotherapy [234], intravesical chemotherapy, device-assisted therapy (see Section 7.2.1.3.2), and combination therapy (see Section 7.2.3) [235]. Changing from BCG to these options can yield responses in selected cases with BCG treatment failure [232,234-242] (LE: 3).

Treatments other than RC must be considered oncologically inferior in patients with BCG failure at the present time [150,229,230] (LE: 3).

Little is known about the optimal treatment in patients with high-risk tumours who could not complete BCG instillations because of intolerance.

Non-high-grade recurrence after BCG is not considered as BCG failure. Treatment decision should be individualised according to tumour characteristics. It could include chemotherapy or repeat BCG instillations, but the published evidence is very low.

Synergo® Technology

The Synergo® device delivers radiofrequency local radiation: a synergistic tri-modality of local, non-ionising Radiofrequency, RF, a chemotherapy instillation, and tissue hyperthermia – all in one, powerful combination, for treating intermediate and high risk Non-Muscle Invasive Bladder Cancer. A special catheter, carrying an embedded small radio-frequency (RF 915 MHz) antenna and thermocouples (special temperature measuring sensors), is introduced into the urinary bladder.

The distal end of the catheter is connected to the Synergo® computer-embedded device that enables the physician to monitor and control the system activity in real-time.

The antenna controllably radiates the bladder walls, while the thermocouples monitor the bladder wall temperature to help ensure that it is kept at a safe range. Chemotherapeutic agent is instilled through the same catheter and constantly circulated and cooled by the heat exchanger unit of the Synergo® device.

Selective effects of RF on cancer cells include phenotypical changes, the formation of micropores on their membranes, and the loss of adhesion between malignant cells – an influential parameter of tumour growth. The drug can now easily penetrate into, and in between these cells, reaching deeper hidden locations. Studies reveal that with RF, even the more resistant cancer cells, become susceptible to chemotherapy, whereas, the effects of RF are negligible on healthy cells. Tissue heating, hyperthermia, is a welcomed by-product of RF. It causes changes in blood perfusion and ruptures in blood supply to malignant cells, as well as unfolding and denaturing of proteins, causing irreparable damages to the DNA selectively in cancer cells. Temperatures of approximately 42 degrees Centigrade, 107 Fahrenheit, are monitored and maintained throughout the treatment.

Temperature elevation of the bladder walls to 42±2ºC enhances the effectiveness of chemotherapeutic agents through several mechanisms additional to those identified in-vitro, including improved tissue penetration and altered immunological response.

May 2017 was bladder cancer awareness month!
Bladder cancer is the fifth most common cancer in the Western world and the second most frequent malignancy of the urinary tract after prostate cancer.

Erlangen Urology meeting 2014

The last urology meeting in Erlangen was well organized and the Synergo® RITE was well located! Few words in German for those who came to share experience and also just to express their interest. Below is Ms. Reich and her booth neighbour dressed in traditional Bavarian costume.

Es ist uns eine Freude, unsere neuen erfahrenen klinischen Fachleute im Team von Synergo® willkommen zu heißen, die uns bei der Ausdehnung unserer Aktivitäten mit urologischen Kliniken in Deutschland und Österreich helfen werden. Unser Ziel besteht darin, urologischen Kliniken eine Verbesserung von Ausbildung, Service und Unterstützung zu bieten. Wir erweitern unsere Aktivitäten mit der Synergo® Technologie, die überall auf der Welt zunehmend routinemäßig für die Behandlung von Patienten mit Blasenkrebs im mittleren Stadium oder mit hohem Risiko eingesetzt wird.

Frau Naama Reich, unsere medizinische Kontaktperson,  

40. Gemeinsamen Tagung der Bayerischen Urologenvereinigung sowie der Österreichischen Gesellschaft für Urologie und Andrologie zu treffen. Erlangen (Germany) 2014

Synergo® RITE (durch Radiofrequenz induzierter Thermo-Chemotherapie-Effekt) gegen nicht muskel-invasiven Blasenkrebs. 

Synergo at the EAU Annual Meeting 2014

EAU Annual Meeting, April 2014

Medical Enterprises thanks the urology colleagues, teams and organizers for the successful EAU congress in Stockholm this month. The congress was very successful and fruitful. Also many thanks for the new visitors who expressed their interest in the Synergo system.

2 poster sessions were presented at the EAU meeting this year by Mr. Issa and Mr. Nair from the UK. 

Challenging the gold standard: A comparison of long-term disease specific outcomes for high-risk non-muscle invasive bladder cancer treated with mitomycin hyperthermia and radical cystectomy:

A prospective single-centre review of 96 patients receiving Synergo MMC-HT and matched against 47 cases undergoing RC for High-Risk Non-Muscle Invasive Bladder Cancer. Charlson co-morbidity Index (CCI), and peri- and post-procedure complications were recorded in each group. Post operative pathology, recurrence and progression rates together with five-year overall and disease specific survival were evaluated.

The mean CCI score for patients receiving MMC-HT was significantly higher than RC group (6.1 vs 4.3). Significant complication rates classified as a Clavian-Dindo score of greater than 2, was significantly higher in the RC cohort (21 percent) compared to patients receiving MMC-HT (0 percent).

There were no deaths associated with MMC-HT treatment compared to a ninety-day mortality of four percent in those receiving RC.

Median follow-up was 36 months (3 to 88 months) for both cohorts. Disease specific survival at five years was observed at 85.2 and 74.6 percent in the MMC-HT and the RC cohorts respectively, whilst overall survival figures were 61.9 versus 68.4 percent.

Conclusions: "MMC-HT is both feasible and safe if offered to well selected patients. It provides durable long-term outcomes compared to RC for HR-NMIBC.....there is a clear advantage in complication rates favouring MMC-HT over RC without a significant difference in disease specific or overall survival."

The efficacy and safety of mitomycin-C hyperthermia in the treatment of high risk (HR) non-muscle invasive bladder cancer (NMIBC) in a single regional centre.

A report on seven year experience of MMC-HT, and aim to establish whether it is efficacious in this high risk cohort of patients.

100 patients with HR NMIBC were treated with MMC-HT (3 patients did not complete induction regimen due to side effects,  1 patient developed clinical metastases during the first two weeks of induction course).  96 patients completed induction treatment and had cystoscopy and biopsy at 3 months.  Of these 96 patients, 84 had failed BCG or were intolerant to it.  Patients were given an induction regimen with weekly treatments for 6-8 weeks with MMC-H on an outpatient basis with the Synergo® system SB-TS 101.

Median follow up was 34 months (3 to 88 months). 72% of patients (69/96) had complete response at 3 months, 10% had partial response (10/96) and 18% (17/96) had recurrence. Twenty patients had radical cystectomy.  Eighteen patients had organ confined disease and two patients had T3 disease at histology.  Only one patient developed recurrence of disease after cystectomy. No patients suffered a Clavien-Dindo Complication above 2.

Conclusions: "MMC-HT has comparable five year survival to radical cystectomy in the treatment of high risk superficial bladder cancer after BCG failure. It is well tolerated and can be delivered effectively by a regional centre. In those patients who are medically fit, cystectomy is still a potentially curative option for those patients who fail MMC-HT." 

What is RITE (Radiofrequency-Induced Thermo-chemotherapy Effect) for bladder cancer?

Hyperthermia is being used in many medical fields.

Synergo® uses a unique combination of local microwave energy hyperthermia (heating) with simultaneous instillation of cooled chemotherapeutic drug. The target of hyperthermia is to reach effective temperature inside the tissue to enable higher drug penetration and accelerate drug-DNA reactions.

Tissue heating should be adjusted per patient and dynamically maintained during treatment while the tissue temperature is constantly measured and closely followed.

Conduction is governed by the Boltzmann equation: Heat conduction is proportional to a constant K which cannot be changed: (for example: Kfat=0.2, Kmuscle=0.38, Ksilver=420)

Since the bladder wall acts as a good thermal insulator, heat penetration from heated liquid is not efficient (conduction/convection heating). On the other hand, during microwave heating the energy is absorbed directly deep in the tissue to enable efficient homogeneous heating, real-time measurement and follow-up on the tissue temperature and dynamic adjustment of the transmitted energy for each per patient over time (e.g. when blood flow in tissue is increased due to heating).

Warm liquid does not allow any simple adjustments in order to tailor heating per patient over time (e.g. different patients have different blood circulation, different tissues, dynamic changes that occur over time such as vasodilation etc.)

Moving from hot liquid to microwave radiation in the Synergo® systems was based on previous experience, as well as on articles already published by other researchers.

Richmond A. Owusu et. al describes the effect and mechanism of hyperthermia together with intravescical chemotherapy in his recently published paper (Owusu et al. 2013)."HT has cytotoxic effects on tumour cells via several mechanisms including improved anti-tumour immunity and by direct cytotoxic effects. Heat plays a role in causing cytotoxicity to tumours (additive effect), enhancing drug toxicity to tumours (synergistic effect), and thermosensitization by noncytotoxic drugs....”

Studies, showing the effect of the Synergo® RITE were performed in the 90's by Paroni et.al. (Paroni et al. 1997; Paroni et al. 2001). The findings indicated the clinical effectiveness benefits of RF hyperthermia associated with chemotherapy. The marked effect on bladder wall permeability resulted in enhanced MMC penetration through the urothelium and the tissue layers. It also showed that the dose administered in the Synergo treatment with hyperthermia, consisting of two 30-minute dwell periods of 20 mg MMC each, actually represented a total dose of not less than 40 mg for the 60 minutes treatment. The same study also showed that the MMC solution is not affected by the RITE method.

The re-fueling of the bladder with a fresh instillation of 20 mg MMC solution (following 30 minutes of treatment) after the bladder is drained of residual urine – eliminates the dilution of the drug with urine and thereby maintains a more optimal and homogeneous drug dose throughout the entire treatment duration. This technique also minimizes the inter-patient variability of parameters such as concentration in residual urine and bladder MMC concentration.

Another study made on animals, showed that indeed bladder walls are heated while adjacent organs are not (Rath-Wolfson et al. 2003). It also showed the evenly distributed heating and that the thermometers of the Synergo® reflect faithfully and accurately the temperature of the tissue and not of the liquid in the bladder vault.

In a 2004 study van der Heijden at al. assessed the effect of hyperthermia on mitomycin C-induced cytotoxicity in bladder cancer cell lines (van der Heijden et al. 2004) showing a decrease in cell proliferation after treatment with increasing concentrations MMC. The apparent synergy of chemotherapeutics and hyperthermia was further addressed by the same group demonstrating a similar phenomenon for epirubicin, EO9, mitomycin C and, to a lesser extent, gemcitabine (van der Heijden et al. 2005).

Owusu RA, Abern MR, Inman BA. 2013. Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer. BioMed Research International 2013: 7. Paroni R, Arcelloni C, De Vecchi E, Fermo I, Mauri D, Colombo R. 1997. Plasma mitomycin C concentrations determined by HPLC coupled to solid-phase extraction. Clinical chemistry 43: 615-618. Paroni R, Salonia A, Lev A, Da Pozzo LF, Cighetti G, Montorsi F, Rigatti P, Colombo R. 2001. Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma. British journal of clinical pharmacology 52: 273-278. Rath-Wolfson L, Moskovitz B, Dekel Y, Kugel V, Koren R. 2003. Combined intravesical hyperthermia and mitomycin chemotherapy: a preliminary in vivo study. International journal of experimental pathology 84: 145-152. van der Heijden AG, Jansen CF, Verhaegh G, O'Donnell M A, Schalken JA, Witjes JA. 2004. The effect of hyperthermia on mitomycin-C induced cytotoxicity in four human bladder cancer cell lines. European urology 46: 670-674. van der Heijden AG, Verhaegh G, Jansen CF, Schalken JA, Witjes JA. 2005. Effect of hyperthermia on the cytotoxicity of 4 chemotherapeutic agents currently used for the treatment of transitional cell carcinoma of the bladder: an in vitro study. The Journal of urology 173: 1375-1380.

Bladder cancer and Synergo latest updates

Bladder Cancer   Bladder cancer is the fourth most common non-dermatological cancer in men in the UK. In 2005, the estimated male and female crude incidence rates of bladder cancer were 24.6 and 9.3 per 100,000 population with 6091 and 2403 new cases, respectively, in England. In Wales the incidence is 43.0 and 17.2 per 100,000 population, that is 619 and 260 new cases, respectively. Altogether, more than 10,000 people in the UK are newly diagnosed with bladder cancer each year. Around 75–85% of these patients have non-muscle-invasive bladder cancer (NMIBC) including carcinoma in situ (CIS). NMIBC has a probability of recurrence at 5 years of up to 80% and a probability of progression of between 0.8% and 30% after initial treatment (depending on the stage and grade of disease). A combined analysis of 2596 patients from seven EORTC Trials with stage Ta T1 Bladder Cancer indicated a 70% recurrence within 3 years (Sylvester R. Eur Urol 2006) Patients with bladder cancer are differentiated into one of three groups: (1) those with low risk disease in whom the main risk is recurrent low-risk papillary disease with a small chance of dying of the disease; (2) those with intermediate and high-risk non-muscle-invasive disease and CIS in whom there is a high chance of disease progression and subsequent death from bladder cancer; and (3) those with muscle-invasive disease in whom there is imminent risk of death from bladder cancer. The goals of current treatment for patients with non-muscle-invasive bladder cancer are to prevent disease recurrence or progression to muscle-invasive disease, to avoid cystectomy and, ultimately, to enhance survival. Transurethral resection of the bladder tumour (TURBT) is the first-line treatment for patients with NMIBC. Unfortunately, the high rate of recurrence and progression after TURBT necessitates the use of adjuvant treatments. This entails instillation of a chemotherapeutic agent, usually mitomycin (MMC), or immunotherapeutic agents such as BCG, either alone or in various combinations. Intravesical BCG is the an effective treatment but patients who fail BCG treatment are often treated again with low probability to remain disease-free and are often referred to cystectomy. Some patients are unable to tolerate BCG and/or are refractory to treatment and some patients cannot receive treatment due to impaired immune system (e.g. lung/kidney transplants). Synergo technology has become a therapy option[1] in many centres throughout Europe for: ·         intermediate and high-risk patients with recurrent tumours, especially after failed BCG treatment ·         patients who are unsuitable or refuse radical cystectomy ·         patients who are unfit for operation ·         patients for whom BCG treatment is contraindicated. [1] Lammers RJ, Witjes JA, Inman BA, Leibovitch I, Laufer M, Nativ O, Colombo R: The Role of a Combined Regimen With Intravesical Chemotherapy and Hyperthermia in the Management of Non-muscle-invasive Bladder Cancer: A Systematic Review. Eur Urol 2011, 60:81-93 Here is some good information to read http://www.cancer.gov/cancertopics/pdq/treatment/bladder/HealthProfessional/page6