Photodiagnosis and Photodynamic Therapy (2004) 1, 103—105
SHORT COMMUNICATION
Renal sparing treatment of upper tract malignant urothelial tumours using photodynamic therapy (PDT)–—three case reports L.M. Coombs, MB, FRCS (FRCS Urol), MD a , Kate Dixon, BA (Hons) b,* a
Northern Lincolnshire & Goole Hospitals NHS Trust, Goole, East Yorkshire, UK The Yorkshire Laser Centre, Goole & District Hospital, Woodland Avenue, Goole, East Yorkshire DN14 6RX, UK
b
KEYWORDS Urothelial cancer; Photodynamic therapy; Urinary tract
Summary Urothelial cancers of the upper urinary tract are usually treated by excision of the kidney, ureter and cuff of the bladder on the affected side. These three cases demonstrate the feasibility, safety and efficacy of photodynamic therapy as a renal sparing procedure for urothelial tumours. © 2004 Elsevier B.V. All rights reserved.
Introduction The mainstay of treatment for urothelial tumours of the upper urinary tract remains excision of the kidney and ureter with a cuff of bladder on the affected side. This major ablative surgery may be employed for tumours that in other sites of the body would be treated with ‘‘cauterisation’’. In the past this led to modified renal sparing surgery with interposition grafts of the bladder, bowel and appendix. Latterly with the advent of robust flexible ureteroscopes treatment has been attempted with thermal lasers and cautery. These treatment modalities are relatively uncontrolled and the depth of tissue injury can lead to perforation or incomplete ablation [1]. The selective uptake of photo sensitisers and subsequent tissue destruction of photodynamic therapy offers a more regulated modality of renal sparing treatment. The efficacy of PDT in urothe-
∗ Corresponding
author.
lial tumours of the bladder has been previously reported [2,3]. A continued concern is the risk of fibrosis of the ureter and obstruction of the kidney. Photofrin® (Porfimer sodium) PDT has been shown in vivo to have less potential to cause fibrosis than heat or radiation [4] and, therefore, was selected for managing three patients with upper tract urothelial cancers.
Method of treatment The patient is generally assessed and urologically investigated. Endoscopic topography and extent of the tumour are mapped out and its histology determined. Following information on PDT and instruction in the precautions necessary to avoid light exposure after sensitisation the patient is given an intravenous injection of Photofrin® (Porfimer sodium) 2 mg/kg of body weight. The tumour is then exposed to red light at 630 nm illumination via a diode laser (Diomed). This is done 48—72 h after administration of the photo sensitiser, using an optical fibre
1572-1000/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/S1572-1000(04)00015-8
104 with a cylindrical diffuser at its end which is passed through the biopsy channel of the cystoscope. Further illumination is carried out 3 days later to map out the residual tumour.
Case 1 A 72-year-old man with a 4-year history of recurrent transitional cell carcinoma (G2,pT1) presented with a similar recurrence extruding out of the right ureteric orifice from the intramural ureter. Intravenous urography and MRI scan confirmed the superficial and local nature of the lesion. He was judged a too high risk for any form of anaesthesia. After administration of Photofrin® under local anaesthesia, using a standard flexible cystoscope a 0.5 cm diffusing fibre was introduced into the right ureteric orifice and red light delivered at 0.2 W for 250 s (100 J/cm of the diffuser). The treatment was repeated at 3 days when it was observed that the tumour was necrosing. At 1 month there was evidence of an old haemorrhagic lesion within the lower ureter. At 2 years there has been no further recurrences around or in the right ureter and the meatus look normal with no reflux.
L.M. Coombs, K. Dixon
Case 2 A 72-year-old lady presented with painless haematuria. Ultrasound and intravenous urography demonstrated a lobulated lesion in the right upper pole calyx (Fig 1a). Rigid ureteroscopy failed to demonstrate a lesion but retrograde studies confirmed its presence. Using a DURA 8 (ACMI) flexible ureteroscope it was possible to enter the upper pole calyx through a narrow infundibulum. An obvious multifocal superficial lesion was seen and confirmed as transitional cell carcinoma by analysis of washing from the calyx. CT scanning supported these observations and DMSA scanning identified a small scar in the upper pole. After sensitisation by intravenous injection of Photofrin® , 2 mg/kg of body weight the tumour was exposed to red light using an optical fibre with 2.5 cm end diffuser passed through the biopsy channel of the cystoscope. Energy used was 100 J/cm of the tumour delivering red light (630 nm) generated by a Diode laser. Illumination was repeated at 3 days and the tumour was noted to be necrosed with some scattered suburothelial haemorrhage elsewhere in the calyx. At ureteroscopy 2 months later there was a small old blood clot but no evidence of tumour. This was supported by repeat intravenous urogra-
Figure 1 (a) Intravenous urography X-ray showing lobulated lesion in the right upper pole calyx (case 2) prior to PDT. (b) Intravenous urography of case 2 following PDT showing no scarring or dysfunction.
Photodynamic therapy phy (IVU) (Fig. 1b) and DMSA scanning showing no scarring or dysfunction. The patient is tumour free to date, 6 months, after PDT.
Case 3 A 70-year-old man with a previous history of transitional cell carcinoma (G1-2,pT1) of the bladder at the right ureteric orifice was found to have multifocal tumour of the right renal pelvis. Ureteroscopy confirmed the presence of two apparently superficial tumours in the renal pelvis. CT scanning supported these observations. DMSA scanning showed unrelated multifocal cortical scarring. After photo sensitisation using intravenous Photofrin® (Porfimer sodium) the renal pelvis was exposed to the red light (630 nm) using an optical fibre with end diffuser of 2.5 cm. The fibre was then placed in each tumour mass for 100 J/cm of the diffuser. Three days later the tumours could be seen to be necrosing and were illuminated again. Follow up DMSA scanning showed no further scarring other than that which was seen at pre PDT examination. Due to an unrelated event the patient’s reassessment was delayed to 4 months. At this time ureteroscopy showed that the original cancer masses had been destroyed but other tumours were noted at the pelviureteric junction. Because of the rapid recurrence of the disease and the long period of photosensitivity with each treatment it was felt inappropriate to use further PDT.
Commentary Photodynamic therapy has been demonstrated to be a feasible, safe and effective mode of treatment in each of these cases with upper urinary tract malig-
105 nant lesions in this small series. In two cases major surgery has been avoided. The last case highlights one of the limitations of photodynamic therapy as a treatment for urothelial cancers. That is, notwithstanding the efficacy of the treatment, the multi focal nature of such tumours makes the targeting difficult. However, with careful monitoring during the PDT procedure and close supervision of patient at follow ups, the recurrence or appearance of a metachronous cancer can be discovered and re-treated by PDT or other therapeutic modalities. At the present time there are no licensed and proven short acting intravenous sensitisers and local application of the sensitising agent is laborious limiting its clinical value. There is, therefore, a pressing clinical need for a short acting easily applied sensitiser, which may be used repeatedly and safely.
Acknowledgements The authors wish to acknowledge Mrs Janet Melvin and Mrs Liz Binnington for their secretarial assistance.
References [1] Walsh R, Vaughan W. Cambells urology, 8th ed. 2003. p. 2845—75 [chapter 80]. [2] Kelly JF, Snell ME. Haematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J Urol 1976;115:150—1511. [3] Nseyo UO, Douhgerty TJ, Sullivan L. Photodynamic therapy in the management of resistant lower urinary tract carcinoma. Cancer 1987;60:3113—9. [4] Shackley DC, Haylett A, Whitehurst C, et al. Comparison of the cellular molecular stress responses after treatments used in bladder cancer. BJU Int 2002;90:924—32.
SHORT COMMUNICATION
Renal sparing treatment of upper tract malignant urothelial tumours using photodynamic therapy (PDT)–—three case reports L.M. Coombs, MB, FRCS (FRCS Urol), MD a , Kate Dixon, BA (Hons) b,* a
Northern Lincolnshire & Goole Hospitals NHS Trust, Goole, East Yorkshire, UK The Yorkshire Laser Centre, Goole & District Hospital, Woodland Avenue, Goole, East Yorkshire DN14 6RX, UK
b
KEYWORDS Urothelial cancer; Photodynamic therapy; Urinary tract
Summary Urothelial cancers of the upper urinary tract are usually treated by excision of the kidney, ureter and cuff of the bladder on the affected side. These three cases demonstrate the feasibility, safety and efficacy of photodynamic therapy as a renal sparing procedure for urothelial tumours. © 2004 Elsevier B.V. All rights reserved.
Introduction The mainstay of treatment for urothelial tumours of the upper urinary tract remains excision of the kidney and ureter with a cuff of bladder on the affected side. This major ablative surgery may be employed for tumours that in other sites of the body would be treated with ‘‘cauterisation’’. In the past this led to modified renal sparing surgery with interposition grafts of the bladder, bowel and appendix. Latterly with the advent of robust flexible ureteroscopes treatment has been attempted with thermal lasers and cautery. These treatment modalities are relatively uncontrolled and the depth of tissue injury can lead to perforation or incomplete ablation [1]. The selective uptake of photo sensitisers and subsequent tissue destruction of photodynamic therapy offers a more regulated modality of renal sparing treatment. The efficacy of PDT in urothe-
∗ Corresponding
author.
lial tumours of the bladder has been previously reported [2,3]. A continued concern is the risk of fibrosis of the ureter and obstruction of the kidney. Photofrin® (Porfimer sodium) PDT has been shown in vivo to have less potential to cause fibrosis than heat or radiation [4] and, therefore, was selected for managing three patients with upper tract urothelial cancers.
Method of treatment The patient is generally assessed and urologically investigated. Endoscopic topography and extent of the tumour are mapped out and its histology determined. Following information on PDT and instruction in the precautions necessary to avoid light exposure after sensitisation the patient is given an intravenous injection of Photofrin® (Porfimer sodium) 2 mg/kg of body weight. The tumour is then exposed to red light at 630 nm illumination via a diode laser (Diomed). This is done 48—72 h after administration of the photo sensitiser, using an optical fibre
1572-1000/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/S1572-1000(04)00015-8
104 with a cylindrical diffuser at its end which is passed through the biopsy channel of the cystoscope. Further illumination is carried out 3 days later to map out the residual tumour.
Case 1 A 72-year-old man with a 4-year history of recurrent transitional cell carcinoma (G2,pT1) presented with a similar recurrence extruding out of the right ureteric orifice from the intramural ureter. Intravenous urography and MRI scan confirmed the superficial and local nature of the lesion. He was judged a too high risk for any form of anaesthesia. After administration of Photofrin® under local anaesthesia, using a standard flexible cystoscope a 0.5 cm diffusing fibre was introduced into the right ureteric orifice and red light delivered at 0.2 W for 250 s (100 J/cm of the diffuser). The treatment was repeated at 3 days when it was observed that the tumour was necrosing. At 1 month there was evidence of an old haemorrhagic lesion within the lower ureter. At 2 years there has been no further recurrences around or in the right ureter and the meatus look normal with no reflux.
L.M. Coombs, K. Dixon
Case 2 A 72-year-old lady presented with painless haematuria. Ultrasound and intravenous urography demonstrated a lobulated lesion in the right upper pole calyx (Fig 1a). Rigid ureteroscopy failed to demonstrate a lesion but retrograde studies confirmed its presence. Using a DURA 8 (ACMI) flexible ureteroscope it was possible to enter the upper pole calyx through a narrow infundibulum. An obvious multifocal superficial lesion was seen and confirmed as transitional cell carcinoma by analysis of washing from the calyx. CT scanning supported these observations and DMSA scanning identified a small scar in the upper pole. After sensitisation by intravenous injection of Photofrin® , 2 mg/kg of body weight the tumour was exposed to red light using an optical fibre with 2.5 cm end diffuser passed through the biopsy channel of the cystoscope. Energy used was 100 J/cm of the tumour delivering red light (630 nm) generated by a Diode laser. Illumination was repeated at 3 days and the tumour was noted to be necrosed with some scattered suburothelial haemorrhage elsewhere in the calyx. At ureteroscopy 2 months later there was a small old blood clot but no evidence of tumour. This was supported by repeat intravenous urogra-
Figure 1 (a) Intravenous urography X-ray showing lobulated lesion in the right upper pole calyx (case 2) prior to PDT. (b) Intravenous urography of case 2 following PDT showing no scarring or dysfunction.
Photodynamic therapy phy (IVU) (Fig. 1b) and DMSA scanning showing no scarring or dysfunction. The patient is tumour free to date, 6 months, after PDT.
Case 3 A 70-year-old man with a previous history of transitional cell carcinoma (G1-2,pT1) of the bladder at the right ureteric orifice was found to have multifocal tumour of the right renal pelvis. Ureteroscopy confirmed the presence of two apparently superficial tumours in the renal pelvis. CT scanning supported these observations. DMSA scanning showed unrelated multifocal cortical scarring. After photo sensitisation using intravenous Photofrin® (Porfimer sodium) the renal pelvis was exposed to the red light (630 nm) using an optical fibre with end diffuser of 2.5 cm. The fibre was then placed in each tumour mass for 100 J/cm of the diffuser. Three days later the tumours could be seen to be necrosing and were illuminated again. Follow up DMSA scanning showed no further scarring other than that which was seen at pre PDT examination. Due to an unrelated event the patient’s reassessment was delayed to 4 months. At this time ureteroscopy showed that the original cancer masses had been destroyed but other tumours were noted at the pelviureteric junction. Because of the rapid recurrence of the disease and the long period of photosensitivity with each treatment it was felt inappropriate to use further PDT.
Commentary Photodynamic therapy has been demonstrated to be a feasible, safe and effective mode of treatment in each of these cases with upper urinary tract malig-
105 nant lesions in this small series. In two cases major surgery has been avoided. The last case highlights one of the limitations of photodynamic therapy as a treatment for urothelial cancers. That is, notwithstanding the efficacy of the treatment, the multi focal nature of such tumours makes the targeting difficult. However, with careful monitoring during the PDT procedure and close supervision of patient at follow ups, the recurrence or appearance of a metachronous cancer can be discovered and re-treated by PDT or other therapeutic modalities. At the present time there are no licensed and proven short acting intravenous sensitisers and local application of the sensitising agent is laborious limiting its clinical value. There is, therefore, a pressing clinical need for a short acting easily applied sensitiser, which may be used repeatedly and safely.
Acknowledgements The authors wish to acknowledge Mrs Janet Melvin and Mrs Liz Binnington for their secretarial assistance.
References [1] Walsh R, Vaughan W. Cambells urology, 8th ed. 2003. p. 2845—75 [chapter 80]. [2] Kelly JF, Snell ME. Haematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J Urol 1976;115:150—1511. [3] Nseyo UO, Douhgerty TJ, Sullivan L. Photodynamic therapy in the management of resistant lower urinary tract carcinoma. Cancer 1987;60:3113—9. [4] Shackley DC, Haylett A, Whitehurst C, et al. Comparison of the cellular molecular stress responses after treatments used in bladder cancer. BJU Int 2002;90:924—32.
