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Keywords:

  • Prostate cancer;
  • brachytherapy;
  • morbidity

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Objective

To report the short-term morbidity and acceptability of the first 50 patients treated with the percutaneous implantation of radioactive iodine seeds for localized carcinoma of the prostate at the Cookridge Hospital.

Patients and methods

Fifty patients were treated with transrectal ultrasonography-guided percutaneous implants with radioactive (125I) iodine seeds for localized carcinoma of the prostate. The mean hospital stay was 36 h and most patients were able to return to work or normal activity within one week of implantation.

Results

All patients developed urethritis which was most marked within the first 3 months of treatment; 8% of patients developed acute retention which resolved after temporary catheterization. At 3 months, 36% of patients still had moderate frequency and 18% moderate dysuria, but by 12 months these had resolved and only 5% of patients still complained of moderate nocturia. There were no cases of incontinence. The incidence of proctitis was very low, with only 2% still complaining of moderate symptoms at one year. Of those potent before implantation, 72% retained potency at one year.

Conclusions

Although it is too early to comment either on late morbidity or on outcome, the results of this study show a side-effect profile similar to that reported by other centres using the same technique.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

In the 1970s and early 1980s, iodine seed implantation for localized prostate carcinoma was performed by surgical exposure of the prostate and manual placement of iodine seeds (125I) into the exposed gland. It was very difficult to achieve a satisfactory distribution of iodine seeds and, as a result, ‘hot’ and ‘cold’ spots within the implanted volume were common, and resulted in either unacceptable morbidity or recurrence [1].

In the last few years improved techniques using TRUS-guided seed placement have allowed percutaneous transperineal implantation of radioactive seeds into the prostate, with the help of a template that ensures accurate seed position within the target volume of implantation [2]. This technique now facilitates satisfactory seed distribution in the vast majority of cases and it can be accomplished with a relatively atraumatic procedure which can often be performed as a day-case. The aim of the current investigation was to describe the short-term morbidity and acceptability of the first 50 patients treated with this new technique at Cookridge Hospital, Leeds.

Patients and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Patients selected for 125I seed implantation met the following criteria: (i) aged <75 years or with a life expectancy ≥10 years; (ii) disease confined within the prostate gland, as determined by TRUS and/or endorectal MRI; (iii) a negative bone scan; (iv) no lymphadenopathy detectable on CT or MRI; (v) a PSA level of <50 ng/mL; (vi) a prostate volume of <50 mL; (vii) no previous TURP.

The patients ranged in age from 46 to 74 years, with 40% younger than 65 and the remainder 65–75 years; 60% had a PSA level at presentation of >10 ng/mL, the level being >20 ng/mL in 32%. Several patients had significant comorbidity which made them unsuitable either for radical surgery or for radical EBRT. Three patients had severe chronic obstructive airway disease and one had had a myocardial infarct 2 years before treatment, both of which were considered contraindications to surgery. Two other patients had inflammatory bowel disease and one a large inguinal hernia, which were relative contraindications to radical EBRT.

Because patients presented with prostatic outflow symptoms rather than through PSA screening, many had enlargement of the prostate from associated BPH; 48% of patients therefore had an initial prostate volume of >50 mL, but otherwise fulfilled the selection criteria. These patients received 3 months of hormone treatment to reduce the volume of the gland before proceeding with their implantation; effectively, they had neoadjuvant hormone therapy, although this was not the main intention.

Treatment technique

Before implantation each patient attended for an estimate of prostate volume by TRUS, performed to plan the exact number and position of seeds required for implantation. The aim was to include the whole prostate plus a 2–3 mm margin outside the capsule, defined on ultrasonography, by an isodose which delivered a minimum of 160 Gy to the periphery of the target volume. After 4–6 weeks, the patient was admitted for the implant which was placed under both general and spinal anaesthesia. Needles were implanted according to their pre-planned position and inserted accurately with the aid of the template co-ordinates and real-time ultrasonography during the procedure. Between 15 and 35 needles were used to deliver 50–120 125I seeds into the prostate. The implanted volume varied from 22 to 49 mL. The first few implants took 3–4 h (or more) but the implantation is currently usually completed within 2 h. Patients were initially hospitalized for 3–4 days but subsequently the mean duration of stay was 36 h and several patients have been able to leave hospital on the same day as the implantation.

Patients were assessed at 4–6 weeks, 3, 4 and 6 months after brachytherapy, and at each visit prospectively completed detailed questionnaires on their symptoms and quality of life. Because the 125I seeds have a half-life of 60 days, the dose of radiation accumulates relatively slowly and declines slowly; thus symptoms were also recorded at 3, 6, 12 and 18 months from implantation. Patients scored their symptoms as nil, mild, moderate or severe. For dysuria this is entirely subjective. Frequency was classed as mild if <2-hourly, moderate if 1–2-hourly and severe if more frequently than hourly. Nocturia was classed as mild if 2–3 times, moderate if 4–5 times and severe if >6 times. Proctitis was classed as mild if bowel frequency was only once or twice each day with minimal discomfort, moderate if three to four times per day requiring treatment and severe if more than five times.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Acute morbidity occurred in two patients (4%), who developed a haematoma in the perineum which required 1–2 weeks to resolve spontaneously, requiring only simple symptomatic treatment. Four of the first 50 patients (8%) developed acute retention within 1–4 days of implantation; all were relieved by placing a urethral catheter and the obstruction resolved in 3–30 days. All patients received prophylactic antibiotics for 10 days after the implant; none developed any sign of urinary or pelvic infection.

Intermediate morbidity is summarized in Table 1. All patients experienced at least mild urinary symptoms in the first 3–6 months. At 3 months, 36% of patients had moderate frequency and 18% moderate dysuria, but by 6 months, only 12% had moderate frequency and 5% moderate dysuria. By one year, no patient had more than mild urinary symptoms; no patient complained of incontinence.

Table 1.  The urinary and bowel side-effects of iodine seed implantation for prostate cancer Thumbnail image of

Very few bowel symptoms were noted (Table 1); three patients had one or two small rectal bleeds within the first week or two of implantation but they settled spontaneously. At 6 months, 15% had mild proctitis and 4% moderate symptoms. At one year, only 5% of patients still complained of mild proctitis. One patient continued to complain of bowel symptoms after one year and eventually developed a recto-urethral fistula. Biopsy from the fistula showed evidence of persistent adenocarcinoma and it is unclear whether this complication was caused by treatment or recurrence or both; it is unlikely to have been due to recurrence alone. Before treatment, 31% of patients were impotent; of those who were potent, 68% remained so after 6 months and 72% after 12 months.

The vast majority of patients were able to return to normal activity by the second or third day after implantation, and were able to return to work; 90% of those in employment were back at work within 2 weeks of brachytherapy.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

It is too early to comment either on late morbidity or on outcome. However, the results of this study show a side-effect profile similar to that reported by other centres using the same technique [3[4][5]–6]. All patients had some degree of urethritis but this was rarely severe; 10–15% of patients reported previously experienced acute retention in the first few days after implantation, compared with 8% in the present series. The follow-up has been too brief to report on potency in the present series; relatively few patients have been followed for >18 months. In other series, potency was preserved for up to 5 years in 60–75% of patients, the variation being largely dependent on age at treatment [7].

As with the present series, the reported incidence of bowel complications from brachytherapy alone is minimal. The one patient who developed a fistula is a source of serious concern, but there have been no further cases of severe bowel damage in 60 patients treated subsequently, and a review of the literature shows that this is an extremely rare event with this technique of implantation.

The morbidity in similar patients treated by radical prostatectomy is reported as a 1–2% perioperative mortality, with 2–3% of patients developing thrombo-embolic complications and 4–5% requiring a second laparotomy for complications. Up to 30% of patients may have some narrowing at the anastomosis which requires dilatation, 3–4% of patients are left with major incontinence and 20–30% still have minor incontinence [8[9][10]–11]. Patient questionnaires have revealed that 80–90% complain of impotence after surgery [12,13]. Most patients treated surgically return home within 10 days; few return to work in <3–4 weeks after surgery.

The results of iodine seed implantation to date show a PSA relapse-free survival equivalent to that achieved by radical surgery in similar patients [14[15]–16]. If this is confirmed by further studies, the convenience and side-effect profile of brachytherapy may make it the preferable option for those patients who are suitable for both procedures.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix
  • 1
    Fowler JeJnr, Barzell W, Hilaris BS, Whitmore Wf. Complications of I-125 implantation and pelvic lymphadenectomy in the treatment of prostatic cancer. J Urol 1979; 121: 44751
  • 2
    Blasko JC, Ragde H, Schumacher D. Transperineal percutaneous iodine 125 implantation for prostate carcinoma using transrectal ultrasound and template guidance. Endocuriether Hypertherm Oncol 1987; 3: 131
  • 3
    Arterbery VE, Wallner K, Roy J, Fuks Z. Short term morbidity from CT planned transperineal iodine 125 prostate implants. Int J Rad Oncol Biol Phys 1993; 25: 6617
  • 4
    Blasko JC, Ragde H, Grimm PD. Transperineal ultrasound guided implantation of the prostate; morbidity and complications. Scand J Urol Nephrol Suppl 1991; 137: 1138
  • 5
    Kaye KW, Olson DJ, Payne JT. Detailed preliminary analysis of iodine 125 implantation for localised prostate cancer using percutaneous approach. J Urol 1995; 153: 10205
  • 6
    Kleinberg L, Wallner K, Roy J et al. Treatment related symptoms during the first year following transperineal I125 prostate implantation. Int J Radiat Oncol Biol Phys 1994; 28: 98590
  • 7
    Stock RG, Stone NN, Iannuzzi C. Sexual potency following interactive ultrasound guided brachytherapy for prostate cancer. Int J Rad Oncol Biol Phys 1996; 35: 26772
  • 8
    Davidson PJ, Van Den Ouden D, Schroeder FH. Radical prostatectomy; prospective assessment of mortality and morbidity. Eur Urol 1996; 29: 16873
  • 9
    Huland H. The risks outweigh the benefits of radical prostatectomy in localised prostate cancer: the argument against. Eur Urol 1996; 29: 313
  • 10
    Haultmann RE, Sauter TW, Wenderoth UK. Radical retropubic prostatectomy; morbidity and urinary incontinence in 418 consecutive cases. Urology 1994; 432: 4751
  • 11
    Leandri P, Rossignol G, Gautier JR et al. Radical retropubic prostatectomy; morbidity and quality of life experience with 620 consecutive cases. J Urol 1992; 147: 8838
  • 12
    Fowler FJ, Barry MJ, Lu-Yoa GL et al. Patient reported complications and follow up treatment after radical prostatectomy. Urology 1993; 42: 6229
  • 13
    Pederson KV, Carlsson P, Rhamquist M, Varenhorst E. Quality of life after radical retropubic prostatectomy for carcinoma of the prostate. Eur Urol 1993; 24: 711
  • 14
    Priestley JB, Beyer DC. Guided brachytherapy for treatment of confined prostate cancer. Urology 1992; 40: 12732
  • 15
    Blasko JC, Wallner K, Grimm PD, Ragde H. Prostate specific antigen based disease control following ultrasound guided iodine 125 implantation for stage T1/T2 prostatic carcinoma. J Urol 1995; 154: 109699
  • 16
    Wallner KE, Roy J, Harrison L. Tumour control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma. J Clin Oncol 1996; 14: 44953

Appendix

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  8. Appendix

Editorial comment

Much of the controversy surrounding the diagnosis and management of early prostate cancer results from the morbidity associated with treatment. Both radical prostatectomy and conventional external beam radiotherapy are major interventions with a substantial risk of complications. Compare the situation with breast and cervical cancer, where one incentive for screening is that early diagnosis of these tumours simplifies the treatment. If we had the equivalent of ‘lumpectomy’ for prostate cancer, the treatment of early prostate cancer would be much easier and, indeed, the case for screening for the disease would be strengthened. While brachytherapy is not comparable with a lumpectomy, Ash et al. are to be commended for pursuing a method of managing early prostate cancer which could offer less risk of morbidity than that associated with conventional curative treatments. They should also be congratulated on their initial results. However, many readers, while welcoming the prospects raised by this paper, may wish to reserve judgement for the present.

The authors clearly select patients for brachytherapy with extreme care. Where different selection criteria are applied for different treatments, cross-modality comparison becomes difficult. Brachytherapy for prostate cancer is not ‘new’; at one time it seemed to have been abandoned, but now it has been revived. In reviewing earlier experience, Herr stated in 1989: ‘What seems unequivocal is that some patients . . . survive without evidence of disease progression for at least 10 years. To what extent this is a consequence of the treatment and to what extent a function of the natural history of the cancer is uncertain’ [1]. The methods used to choose patients for brachytherapy in the present report might have selected tumours with favourable biology. Also, despite the excellent results in these patients at this stage, a longer period of follow-up is needed to ensure that reduced morbidity is not at the expense of an increase in long-term relapse. Thus we cannot really be sure to what extent this method of treatment can replace radical prostatectomy and external beam radiotherapy, nor for which patients it is appropriate.

Some reader may question the values for the morbidity and complications of radical prostatectomy quoted in the paper. They are supported with values from the literature but as a comparison with authors’ results this may be unfair. Neither brachytherapy nor radical prostatectomy are much better than the more general experience quoted here, and equally, the results from brachytherapy obtained by the group at Cookridge Hospital may not necessarily be reproducible elsewhere. Overemphasizing the benefits of brachytherapy may encourage others with less expertise to take it up. Rather that establishing the technique, this could bring it into disrepute. Healthy competition can encourage advance but conflict can be counterproductive; if a slight aura of condemnation of radical prostatectomy can be detected in this paper, urologists should not respond in kind. All involved in the challenge of early prostate cancer must share the goal of finding the right treatment for each patient. To do this, the results from different therapies must be compared accurately, at least on an intention-to-treat basis [2], and ideally by co-operation in randomized trials. Meanwhile, as far as brachytherapy is concerned, we shall await with interest further data on these and other patients receiving this promising treatment.

1 Herr HW. Interstitial irradiation by iodine implantation. In Fitzpatrick JM, Krane RJ, eds. The Prostate. Edinburgh: Churchill Livingstone, 1989: 377–81

2 Lu-Yao GL, Yao S-L. Population based study of long-term survival inpatients with clinically localized prostate cancer. Lancet 1997; 349: 906–10

David Kirk

Gartnavel General Hospital

Scotland