20 Prostate Cancer

Prostate Cancer

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THE GEC ESTRO HANDBOOK OF BRACHYTHERAPY | Part II: Clinical Practice Version 1 - 01/12/2014

Neoadjuvant antiandrogens were shown to have a detrimental effect on outcome. One randomised controlled trial has been reported from Mount Vernon Hospital which compared external beam treatment de- livering 55Gy in 20 daily fractions with a combined schedule of external beam 35.7Gy in 13 fraction and a HDR boost of 17Gy in 2 fractions [68]. There was an advantage in biochemical con- trol for the combined HDR group at 7 years with lower acute rectal morbidity and improved quality of life at 3 months. No increase in late morbidity was seen and this advantage was seen in all three risk groups using the conventional prognostic factors of PSA, Gleason score and T stage. The relative doses of the two schedules in 2Gy equivalents are 62.5Gy and 77.7Gy with an α/β of 3.5 and 66.9Gy and 92.1Gy with an α/β of 1.5. Thus this ran- domised trial supports the cohort data showing that the use of an HDR boost is a highly effective means of achieving biological dose escalation with improved biochemical relapse free survival. Further evidence for the role of HDR brachytherapy as a boost with external beam treatment is found in two case control stud- ies. The first of these from MSKCC compared a cohort of pa- tients receiving high dose IMRT (86.4Gy) with a matched cohort receiving 46Gy with an HDR boost [14]. A significantly better PSA relapse free survival was seen in the HDR group particularly in the intermediate and high risk groups. Similar results were reported from Peter MacCallum Cancer Centre in Melbourne comparing a cohort receiving 74Gy external beam with an HDR boost group matched for major prognostic factors [69]. HDR Monotherapy The first experience with HDR monotherapy was reported from Osaka using a schedule of 48-54Gy in 8-9 fractions in a popu- lation of predominantly high risk patients. The 5 year PSA fail- ure free rate was 70% [70]. A series of 298 patients treated at Oakland and Michigan reports a 94% biochemical control rate at 5 years. This was a relatively good prognosis group having a median presenting PSA of 5.4, stage IC and Gleason score 6 and the two centres used two different schedules, 42Gy in 6 fractions in Oakland and 36Gy in 4 fractions in Michigan. No statistically significant difference between the two schedules was seen [71]. A dose escalation study reporting three cohorts receiving 34Gy in 4 fractions, 36Gy in 4 fractions and 31.5Gy in 3 fractions from Mount Vernon has a 100% biochemical control rate with median follow ups of 30, 18 and 11.8 months respectively [72]. The larg- est published series comes from the Offenbach group reporting on a total of 718 patients receiving 36-38Gy in 4 fractions. Five year biochemical relapse free survival rates of 94% are reported [16]. PDR afterloading brachytherapy Published data on PDR prostate brachytherapy is sparse with no significant long term data yet available. One series of 106 patients delivering PDR dose of 24.96 – 28.8Gy after 46Gy in 23 fractions reports 3 and 5 year biochemical relapse free survivals of 92.8% and 89.5% in a population in which 62% were high risk and the remainder intermediate risk except for 2 low risk patients [73]. Prostate brachytherapy for local recurrence The management of local recurrence after previous radical ra- diotherapy is unsatisfactory [74]. Salvage surgery is associated with considerable operative morbidity with long term effects on

urinary function and continence. Androgen deprivation is time limited in its response and can also be associated with consider- able systemic toxicity. Reirradiation with external beam carries a concern from exceeding tolerance doses to the rectum and blad- der. Brachytherapy is therefore a potentially attractive option for salvage treatment. Experience to date is limited and includes some series which have used combined external beam and brachytherapy as well as brachytherapy alone. There is greatest experience with LDR brachytherapy after external beam but HDR has also been re- ported. Overall local control and biochemical control rates of around 70% are reported. In this setting focal treatment may have a major role sparing uninvolved regions of the prostate and adjacent organs at risk. A number of studies are being undertaken to evaluate this ap- proach using both LDR and HDR. Retreatment after prostate brachytherapy is possible after pre- vious brachytherapy. Current data show that it is a safe and fea- sible treatment when especially focal salvage is performed. This should preferably be performed in a centre with extensive expe- rience in prostate brachytherapy. Temporary haematuria is common with very occasional clot re- tention which is more common after HDR techniques in which applicators are placed at or through the bladder base. Patients should also be warned about perineal bruising. All patients develop urethritis which is mostly mild or moderate. After LDR seed brachytherapy this starts five or six days after implantation and may persist at a decreasing level for six to nine months. Most patients will also notice frequency, urgency and obstructive symptoms. In contrast to LDR when this may persist for 6 to 12 months, after HDR brachytherapy there is an acute phase of urethritis developing in the first two weeks after implan- tation which resolves much more rapidly, usually within 6 weeks from the implant. Acute retention after LDR seed brachytherapy requiring cathe- terisation is seen in between 5 and 15% of patients related main- ly to patient selection. The majority resume normal micturition after 10 to 14 days but some need a catheter for a few months. Surgical intervention should be delayed for as long as possible but if there are still obstructive symptoms after 12 months a tran- surethral incision or channel TURP can be performed. This is safer than a full TURP which carries a significant risk of incon- tinence. Delay until after more than 3 years from implantation may also be associated with a higher chance of incontinence, due to fibrosis. Prognostic factors for obstruction are a high urinary symptom score, large volume and initial hormone therapy to downsize the volume. The dose to the urethra may be more related to irritative than obstructive symptoms [75]. 13. ADVERSE SIDE EFFECTS

Long-term urinary morbidity is rare and related to the factors