The morphological changes in rat bladder after photodynamic therapy with 5-aminolaevulinic acid-induced protoporphyrin IX

OBJECTIVE: To assess the optimum light energy needed to induce only superficial bladder wall damage during photodynamic therapy (PDT) as a treatment for bladder cancer. Materials and methods The urinary bladder (with normal epithelium) of 64 female rats was treated with PDT using a continuous-wave argon-ion laser as an energy source and aminolaevulinic acid (ALA)-induced protoporphyrin IX photosensitizer. Four hours after the intravenous administration of ALA (300 mg/kg) the bladders were intravesically exposed to light fluences of 20-80 J/cm2. The control rats received no ALA and were exposed to 20 J/cm2 light. After 1, 3, 7 and 21 days the animals were killed and the morphological changes in bladder wall analysed both macroscopically and using light and scanning electron microscopy. RESULTS: At the dose of ALA given, a fluence of 20-40 J/cm2 caused mainly superficial damage, whereas 80 J/cm2 produced full-thickness injuries to the bladder wall. The maximum effect of PDT occurred after 1 and 3 days of irradiation. After 3 weeks of PDT the histology showed few full-thickness injuries and only in those treated with 80 J/cm2 light. CONCLUSION: These results indicate that PDT can be used to safely induce a selective superficial removal of bladder mucosa with no fibrotic effects on detrusor musculature, when optimum photosensitizing drug and fluences are used. These findings support the use of PDT in the therapy of superficial bladder cancer.     

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma

OBJECTIVE: To assess the effect of whole-bladder photodynamic therapy (PDT) on a rat model with orthotopic superficial bladder cancer, as PDT is an alternative intravesical therapy for treating superficial bladder cancer, based on an interaction between a photosensitizer and light energy to induce oxygen radicals that destroy tissue by lipid peroxidation. MATERIALS AND METHODS: In all, 76 female Fischer F344 rats were inoculated intravesically with AY-27 tumour cells. After establishing superficial tumour, 24 rats were treated with PDT using aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer, and a continuous-wave argon pumped-dye laser (638 nm). At 4 h after intravenous (300 mg/kg) or intravesical (100 mg/mL) administration of ALA the bladders were intravesically exposed to a 40 J/cm(2) light dose; 12 rats received no ALA but were exposed to the same light dose. Before administering ALA, urine cytology samples were taken for analysis. At 3 or 21 days the treated rats were killed and morphological changes in the bladder walls analysed by light microscopy. Forty rats served as controls to examine the presence of tumour. RESULTS: The tumour established in 33 of 40 rats (83%) in the controls, but after PDT with intravesical ALA there was carcinoma in only in one of 12 (P < 0.001, Pearson's chi(2) test). After PDT with intravenous ALA there was carcinoma in five of 11 rats (P = 0.063, Pearson's chi2 test). In the control group of 12 rats receiving only light energy there was carcinoma in three (P = 0.001, Pearson's chi(2) test). Histologically, at 3 days after PDT there was only mild superficial damage in all six rats treated intravesically. Bladder wall destruction reached the muscular layer, with an abscess in one of six rats treated intravenously. After 3 weeks of PDT there was muscular necrosis with perforation and abscess from catheterization two of six rats treated intravesically and in three the bladder wall totally recovered. In the intravenous group the bladder walls were normal or had only mild superficial damage. Cytology of the urine sediment failed to detect half the tumours in the treatment groups. CONCLUSION: These results support the use of PDT with intravesical ALA-induced protoporphyrin X for treating superficial bladder carcinoma. Intravesical was better than intravenous ALA in eradicating bladder carcinoma with PDT.     

Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

A phase-1 study of sequential mitomycin C and 5-aminolaevulinic acid-mediated photodynamic therapy in recurrent superficial bladder carcinoma

OBJECTIVE: To report a phase-1 study of patients with recurrent superficial bladder cancer treated with photodynamic therapy (PDT) using sequential mitomycin C and 5-aminolaevulinic acid (ALA). PATIENTS AND METHODS: Twenty-four patients were treated, the primary endpoint being the safety and tolerability of combined therapy at increasing doses of ALA and light. RESULTS: Mitomycin C instillation was followed by ALA concentrations of 6%, 8% or 10%; there was no effect on toxicity. The light dose, at a wavelength of 635 nm, was increased from zero to 25 J/cm(2), with the upper fluences producing transient symptoms. There were no episodes of skin photosensitivity or systemic toxicity. A total fluence of 25 J/cm(2) represented the upper light dose for the tolerability of this procedure by patients. There were no persistently high urinary symptom scores or reduction in functional bladder capacity up to > or =24 months of follow-up. In this group, cumulative tumour recurrences were none at 4, two at 8, six at 12, nine at 18 and 11 at 24 months after PDT, respectively. CONCLUSION: Sequential mitomycin C and ALA-PDT is a safe and well tolerated treatment, with potential for managing difficult-to-control superficial transitional cell carcinoma and carcinoma in situ of the bladder.     

Green light photodynamic therapy in the human bladder

We conducted this pilot clinical study to investigate the safety, primarily acute toxicity, of green light (514.5 nm) whole bladder photodynamic therapy (PDT) in human bladders with transitional cell carcinoma. We enrolled five patients who were scheduled to undergo radical cystectomy and urinary diversion for locally muscle invasive bladder cancer. Four patients received intravenous injection of Photofrin at 1 mg/kg, while one patient received no drug, 48 hr before undergoing green light whole bladder photoactivation with light doses of 20-60 J/cm 2. Each patient underwent radical cystectomy on day 7 following light treatment. Post-PDT evaluation included daily monitoring of voiding symptoms, cystometric measurements of bladder capacity, and gross and histopathologic examination of the excised bladders. Our results show that the intensity of acute bladder irritation and acute post-PDT loss in bladder volume depended on the light dose and extent of bladder tumor with the associated inflammation. There was no transmural bladder injury and no treatment related morbidity. These data on acute toxicity suggest that green light whole bladder PDT treatment with 1 mg/kg of Photofrin and 20-40 J/cm 2 of laser power is safe.     

Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumours

OBJECTIVES: To assess (i) the optical properties and depth of penetration of varying wavelengths of light in ex-vivo human bladder tissue, using specimens of normal bladder wall, transitional cell carcinoma (TCC) and bladder tissue after exposure to ionizing radiation; and (ii) to estimate the depth of bladder wall containing cancer that could potentially be treated with intravesical photodynamic therapy (PDT), assuming satisfactory tissue levels of photosensitizer. Materials and methods The study included 11 cystectomy specimens containing invasive TCC (five from patients who had previously received external-beam bladder radiotherapy, but with recurrent TCC) and three 'normal' bladders removed from patients treated by exenteration surgery for extravesical pelvic cancer. Full-thickness bladder wall and tumour samples were taken from these specimens and using an 'intravesical' and a previously validated interstitial model, the optical penetration depths (i.e. the tissue depth at which the light fluence is 37% of incident) were calculated at wavelengths of 633, 673 and 693 nm. RESULTS: There were no significant differences in light penetration between normal and tumour-affected bladder tissue at each wavelength. There were significant differences in light penetration among wavelengths; light at 693 nm penetrated approximately 40% further than light at 633 nm (P < 0.002). The light currently used in bladder PDT (633 nm) has a mean (SEM) optical penetration depth of 4.0 (0.1) mm within TCC. In addition, at this wavelength, there was 29% greater light penetration in previously irradiated than in unirradiated bladder wall (P = 0.001). This did not occur in the tumour-affected bladder. CONCLUSIONS: Bladder tissue is relatively more translucent than other human tissues and there is therefore great potential for PDT in the treatment of bladder cancer. As there is no difference in light penetration between TCC and normal bladder tissue, a tumour-specific response with diffuse illumination of the bladder will depend on drug localization within the tumour. The currently used wavelength of 633 nm can be expected to exert a PDT effect within bladder tumour up to a depth of 20 mm. Increasing the wavelength will allow deeper pathology to be treated.     

光动力疗法对人膀胱癌细胞胞内游离钙的影响

目的:探讨光动力学作用后的膀胱癌细胞(T-24和SCaBER)胞内钙离子浓度的变化.方法:采用MTT比色分析法判断光动力学对体外人膀胱癌T-24和SCaBER细胞的杀伤效应.同时应用激光共聚焦显微镜和Fluo-3/AM探针技术测定光动力学作用后细胞内钙离子的浓度.结果:T-24和SCaBER细胞内钙离子有明显升高,与对照组比较差异有显著意义(P＜0.001).结论:光动力学作用后细胞内钙离子超载可能在细胞死亡中发挥重要作用.     

PHOTODYNAMIC THERAPY USING PORFIMER SODIUM AS AN ALTERNATIVE TO CYSTECTOMY IN PATIENTS WITH REFRACTORY TRANSITIONAL CELL CARCINOMA IN SITU OF THE BLADDER

Purpose

Photodynamic therapy combines a photosensitizer, such as porfimer sodium (Photofrin), with red laser light (630 nm.) to destroy cancer cells. Investigators have reported the effectiveness of photodynamic therapy in the treatment of patients with recurrent superficial bladder cancer. We assess the safety and efficacy of 1 or 2 photodynamic treatments using porfimer sodium and controlled uniform laser light (630 nm.) as an alternative to cystectomy in patients with refractory vesical carcinoma in situ of the bladder.

Materials and Methods

A total of 36 patients with carcinoma in situ were treated with whole bladder photodynamic therapy as an alternative to cystectomy. In all patients at least 1 course of bacillus Calmette-Guerin (BCG) had failed. Each patient received a single whole bladder photodynamic therapy treatment, consisting of 2 mg./kg. porfimer sodium intravenously followed 40 to 50 hours later by intravesical red light (630 nm.) at 15 J./cm.². Post-photodynamic therapy evaluations included weekly telephone contact to assess acute adverse reactions, and assessment of efficacy and bladder toxicity at 3 months and quarterly thereafter.

Results

At initial clinical evaluation at 3 months 58% of the patients had a complete response as indicated by negative cystoscopy, bladder biopsy and urine cytology but in 42% treatment failed. At a mean followup of 12 months (range 9 to 48) 10 of the 21 complete responders had recurrence for an overall durable response rate of 31%. Fourteen patients subsequently underwent cystectomy for persistent carcinoma in situ (12) and carcinoma in situ recurrence (2). Of the 36 patients 7 experienced bladder contracture.

Conclusions

The initial results are encouraging for a single whole bladder photodynamic treatment of patients in whom prior intravesical therapy for carcinoma in situ has failed. While followup is short, porfimer sodium photodynamic therapy appears potentially promising as an alternative to cystectomy in patients with refractory carcinoma in situ.     

Effects of photodynamic therapy in combination with intravesical drugs in a murine bladder tumor model.

This study was designed to evaluate the interaction of photodynamic therapy (PDT) and intravesical drugs (thiotepa, adriamycin, mitomycin C and BCG) in a murine transitional cell carcinoma (MBT-2) model. C3H/He mice with implanted MBT-2 flank tumors were treated with either thiotepa (TT), adriamycin (ADM), mitomycin C, Bacillus Calmette-Guerin (BCG), photodynamic therapy (PDT) or a combination of the drug and PDT. The MBT-2 tumor showed sensitivity to adriamycin, MMC or PDT compared to control. PDT combined with either adriamycin, MMC or BCG, produced a greater retardation in the growth of the MBT-2 tumor than monotherapy with adriamycin, MMC, BCG or PDT. PDT combined with the anticancer agents currently used in intravesical therapy for bladder cancer is well tolerated. The combination of PDT and intravesical drugs may enhance the tumoricidal effect of either treatment used alone.     

茶多酚对人膀胱癌细胞光动力学杀伤效应的影响

目的 :探讨茶多酚对人膀胱癌细胞叶绿素衍生物光动力学杀伤效应的影响。 方法 :采用MTT比色分析法 ,判断茶多酚影响体外人膀胱癌T -2 4和SCaBER细胞光动力学的杀伤效应。 结果:与单纯光动力学作用组比较 ,茶多酚能显著减弱叶绿素衍生物光动力学对两种人膀胱癌细胞的损伤 (P <0 0 5,0 0 1) ,茶多酚的作用时间与光动力学对T -2 4细胞杀伤效应呈负相关 ,而与SCaBER细胞却无相关性。 结论 :茶多酚具有较强的缓解膀胱肿瘤细胞光动力学杀伤效应的作用     

Study of factors mediating effect of photodynamic therapy on bladder in canine bladder model

The canine bladder model was employed to study the factors mediating the effect of photodynamic therapy (PDT) on the bladder. The recovery (time taken for the bladder volume to return to pre-PDT value), gross and microscopic findings, implicate both bladder high filling pressure (60 cm H2O) and high light dose as factors mediating the effect of photodynamic therapy on bladder capacity. We recommend that photodynamic therapy to the bladder be performed under a filling pressure of 30 cm H2O, which is physiologic, and whole bladder illumination at a light dose not greater than 30 J/cm2.     

An ultrastructural study of human bladder cancer treated by photodynamic therapy

An electron microscopic study has been carried out biopsy material of transitional cell carcinoma of human bladder, taken before and after photodynamic therapy (PDT), from 14 patients. It has been demonstrated that bladder cancer is highly sensitive to PDT using haematoporphyrin derivative (HPD, made in China) and laser irradiation. It was found that vascular endothelium within the tumour tissue was very sensitive to PDT, showing distinct changes as early as immediately after completion of a 20-min irradiation. Twenty-four hours after PDT, almost all the capillaries examined were necrotic and broken down into small fragments. The cancer cells were less sensitive to PDT, being damaged later and less seriously than the blood vessels. It has been concluded that in PDT-treated tumours the vascular endothelium is damaged primarily while the cancer cells are destroyed, to a considerable extent, secondarily as the consequence of structural damage to capillaries and functional disturbance in the microcirculation. We would speculate that the main factor influencing the final response is the actual concentration of HPD in various types of cell in the tumours.     

Whole bladder wall photodynamic therapy with in situ light dosimetry for carcinoma in situ of the bladder.

We report on the preliminary results of 12 patients with multifocal carcinoma in situ of the bladder treated with whole bladder wall photodynamic therapy. The total light dose (scattered plus nonscattered light) measured in situ was 100 joules per cm.2 in the first 6 patients (group 1) and 75 joules per cm.2 in the remaining 6 (group 2). These light doses correspond on the average to 27 joules per cm.2 and 15.5 joules per cm.2 nonscattered light as reported by other investigators. Followup ranged from 6 to 22 months (average 11.5). In group 1, 2 tumors recurred after 6 and 9 months, respectively, and 2 other patients had a permanently shrunken bladder without evidence of disease. In group 2, 1 tumor recurred 5 months after photodynamic therapy. In this group the bladder capacity increased on the average to 135% of the pretreatment value 3 months after photodynamic therapy. All recurrences were in patients with a history of invasive bladder cancer (stages T1 and T2). These preliminary results demonstrate the importance of in situ scattered light dosimetry for minimizing local side effects of whole bladder photodynamic therapy.     

Elevations of cytokines interleukin-1, interleukin-2 and tumor necrosis factor in the urine of patients after intravesical bacillus Calmette-Guerin immunotherapy

In an attempt to elucidate further the immunological mechanisms responsible for the effectiveness of intravesical bacillus Calmette-Guerin in the therapy of superficial urothelial bladder cancer, a prospective study was performed in which the urine of patients was examined before and after 6 intravesical instillations of bacillus Calmette-Guerin for the presence of the cytokines interleukin-1, interleukin-2 and tumor necrosis factor-alpha. Biological assays such as specific sandwich enzyme-linked immunosorbent assays were used for the analysis of each cytokine. Urinary titers of interleukin-1, interleukin-2 and tumor necrosis factor increased significantly after bacillus Calmette-Guerin instillation but showed inter-individual differences. The maximum of secretion into the urine was seen between 4 and 8 hours after the instillation, and titers returned to baseline values within 24 hours. The differences in 24-hour secretion between the bacillus Calmette-Guerin-treated (10 patients) and the control (10) groups were significant with respect to all cytokines as tested in both assays each, except for the interleukin-1 biological assay. These results reflect the strong inflammatory response in the bladder wall to bacillus Calmette-Guerin, in which the urinary secretion of the detected cytokines may be associated with the local tumor control.     

Analysis of haematoporphyrin derivative and laser photodynamic therapy of upper gastrointestinal tumours in 52 cases

Fifty-two patients with upper gastrointestinal tumours have been treated by photodynamic therapy (PDT). The argon ion pumped dye laser, with quartz delivery fibre, was made in China. The haematoporphyrin derivative was also synthesized in China. Forty of the 52 patients responded to PDT, a 77% tumour response rate. This technique is safe as there were no severe complications. These results demonstrate the advantages of PDT in the treatment of advanced gastrointestinal cancer.     

Fluorescence detection and photodynamic treatment of photosensitized tumours in special consideration of urology

Most methods of modern laser tumour therapy are physically based on the conversion of light to heat. Recently tumours have also been treated using ionizing processes for tissue ablation. Photodynamic laser therapy (PDT), however, involves light-induced non-thermal biochemical processes and the use of a photosensitizer.Several drugs are known to be stored selectively in tumours after systemic application. This transient marking can be used for diagnostic and therapeutic procedures. The marker most commonly used is dihaematoporphyrin ether/ester (DHE) intravenously injected at doses of 0.2–3.0 mg/kg bodyweight for diagnosis and therapy, respectively. The corresponding clearance intervals after injection of DHE range from 3–48 h to 25–75 h.Detection of photosensitized tumours might offer great advantages. The highly sensitive two-wavelength laser excitation method with computerized fluorescence imaging recently has been transferred to the hospital for clinical tests.Photoinduced production of singlet oxygen is claimed to be the initial process which leads to later tumour destruction and therapy. PDT has been applied to 20 patients suffering from superficial tumours (TIS GII–III) recurred after application of other treatments. The results after PDT were evaluated by three-monthly check-ups (endoscopy, cytology, bladder mapping, renal ultrasonography) as well as by computed tomography (CT) examination at 8–13 month intervals. In six patients treated by PDT no tumour recurrence has been found over the whole observation period of up to 5 years. Four patients have remained free of tumour (12 and 14 months) after repeated transurethral resection (TUR) and Nd-YAG laser therapy following PDT. Due to an initial application of insufficient irradiation four patients required a second PDT. In one patient a circumscribed dysplasia appeared at the left ostium 26 months following PDT and was treated successfully by means of thermal Nd-YAG laser irradiation following TUR. In six patients slight mucosal atypia persisted for a period of at least 2.5 years. One cystectomy had to be performed because of bladder shrinkage. The dissected bladder, however, was free of tumour.These preliminary results suggest that PDT is justified in patients who are in a worst-case situation with cystectomy recommended in case of recurrent superficial TIS bladder carcinoma and indicate the future potential of photodynamic therapy of tumours.Homogeneous irradiation of the area to be treated and a reliable light dosimetry are prerequisites for an effective tumour therapy. Standard instruments for a routine application do not exist, but are under development.     

Photodynamic therapy.

The preliminary data suggest that red-light whole-bladder photodynamic therapy is safe and effective in the treatment of Tis and may be useful in the prophylactic management of superficial bladder cancer. Theoretically, whole-bladder photodynamic therapy has the advantage of higher efficacy after a single treatment than most conventional modalities for superficial bladder cancer. In patients with Tis, the complete response rate is 88%, and 25% have recurrences during a mean follow-up of 20 months (range 12-60). In patients undergoing prophylaxis, the recurrence rate is 31% and the median time to recurrence is 18 months. Importantly, none of the high-risk patients treated with whole-bladder photodynamic therapy has developed disease progression in stage or grade at the time of recurrences. Whole-bladder therapy also has the potential advantage of repeat treatment without increased tumor resistance or increased morbidity. Data from the present phase II-III clinical trials involving a large number of patients will define the role of photodynamic therapy in the management of superficial bladder cancer.     

Photodynamic Therapy on Rat Urinary Bladder with Intravesical Instillation of 5-Aminolevulinic Acid: Light Diffusion and Histological Changes

Purpose

Photodynamic therapy (PDT) has the potential to treat extensive premalignant lesions and microinvasive tumors in the bladder, but its use has been hampered by the risk of detrusor muscle damage and prolonged skin photosensitivity. We have shown that the rat urothelium can be sensitized by selectively using a 10 percent solution of 5-aminolevulinic acid (ALA) at pH 5.5 administered intravesically. This paper evaluates the photodynamic effects on sensitized bladders.

Materials and Methods

The bladders of Wistar rats were instilled with ALA solutions of different concentrations at pH 5.5 and subsequently treated with laser light at 630 nm. Bladders were harvested 1 to 7 days after PDT for histological assessment.

Results

Under optimum conditions (10 percent intralipid diffusion medium, light dose 50J) uniform urothelial necrosis was seen after 1 to 2 days; it healed in 7 days without damage to the underlying muscle layer although some increase in collagen was seen in the lamina propria. Overtreatment or poor light distribution resulted in muscle necrosis and scarring.

Conclusions

Selective urothelial necrosis is possible with PDT using intravesical ALA. There is now sufficient data for pilot clinical trials to start photodynamic therapy for management of superficial bladder cancer or carcinoma in situ.     

The morphological and functional changes in rat bladder following photodynamic therapy with phthalocyanine photosensitization

We have studied photodynamic therapy (PDT) in the rat bladder with a new photosensitizer, aluminium sulfonated phthalocyanine (AlSPc) given intravenously and intravesically. The microscopic distribution of photosensitizer fluorescence in the bladder wall was studied by laser fluorescence microscopy. Prior to PDT the bladder capacity and compliance were assessed by filling cystometry. Intravesical red light (675 nm.) from a copper vapour pumped dye laser was used to activate the photosensitizer using light doses of 20 to 200 J/cm2. Urodynamic and histologic changes were studied at intervals for up to three months. The fluorescence studies showed that AlSPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 hours there was four times as much fluorescence from the mucosa and lamina propria compared to the deeper muscle. Control bladders illuminated with laser light alone showed no effects at these light doses. Animals treated 24 hours after sensitization showed a reduction in bladder capacity of up to 78% (20 J/cm2. light and 1.5 mg./kg.AlSPc). An initial reduction in compliance recovered in two weeks after low doses (0.5 mg./kg.) of AlSPc but was still abnormal at three months after higher doses (1.5 mg./kg.); though there was no long term histologic abnormality seen. Aluminium sulfonated phthalocyanine is a promising photosensitizer for bladder photodynamic therapy and using low doses of the drug it is possible to produce a superficial necrosis without muscle damage across a range of light doses. This heals by epithelial regeneration with no long term functional impairment. Direct absorption of this photosensitizer following intravesical administration seems unreliable.     

Photodynamic therapy (PDT) in early central lung cancer: a treatment option for patients ineligible for surgical resection

OBJECTIVES: To review the Yorkshire Laser Centre experience with bronchoscopic photodynamic therapy (PDT) in early central lung cancer in subjects not eligible for surgery and to discuss diagnostic problems and the indications for PDT in such cases. METHODS: Of 200 patients undergoing bronchoscopic PDT, 21 had early central lung cancer and were entered into a prospective study. Patients underwent standard investigations including white light bronchoscopy in all and autofluorescence bronchoscopy in 12 of the most recent cases. Indications for bronchoscopic PDT were recurrence/metachronous endobronchial lesions following previous treatment with curative intent in 10 patients (11 lesions), ineligibility for surgery because of poor cardiorespiratory function in 8 patients (9 lesions) and declined consent to operation in 3 patients. PDT consisted of intravenous administration of Photofrin 2 mg/kg followed by bronchoscopic illumination 24-48 h later. RESULTS: 29 treatments were performed in 21 patients (23 lesions). There was no procedure-related or 30 day mortality. One patient developed mild skin photosensitivity. All patients expressed satisfaction with the treatment and had a complete response of variable duration. Six patients died at 3-103 months (mean 39.3), three of which were not as a result of cancer. Fifteen patients were alive at 12-82 months. CONCLUSION: Bronchoscopic PDT in early central lung cancer can achieve long disease-free survival and should be considered as a treatment option in those ineligible for resection. Autofluorescence bronchoscopy is a valuable complementary investigation for identification of synchronous lesions and accurate illumination in bronchoscopic PDT.