Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Subcutaneous midazolam infusion in palliative care.

This article describes the use of a subcutaneous infusion of midazolam to control restlessness and agitation in 23 patients during the final stages of advanced cancer. Midazolam effectively controlled symptoms in 22 of the patients at an initial dose of 0.4-0.8 mg/hr rising to a mean maximum dose of 2.9 mg/hr. Midazolam mixed in the same syringe as diamorphine was well tolerated at injection sites. The wide dose range emphasizes the need for careful titration of dose for individual patients. At high doses, the volume of injection required presented some practical difficulties, but otherwise there were no major problems with this technique. Midazolam by subcutaneous infusion is a well-tolerated, safe and effective treatment for terminal restlessness and agitation, and deserves more extensive evaluation.

Epidermoid anal cancer in HIV infected patients.

Anal cancer associated with human immunodeficiency virus (HIV) infection is an unusual clinical situation in which the appropriate management remains unclear. Experience of treatment and follow-up is presented of six patients with histologically confirmed invasive epidermoid anal cancer on a background of HIV infection. Durable complete responses with acceptable toxicity occurred in two patients with moderate immunosuppression and Stage I-II tumours treated with a combination of concomitant chemotherapy (5-fluorouracil and mitomycin-C) and pelvic radiotherapy (45 Gy in 25 fractions). One patient treated with radiotherapy alone (60 Gy in 30 fractions in two phases) had a complete response. Two patients, one with Stage III tumour and the other with pre-existing acquired immunodeficiency syndrome, died within 6 months of treatment. Moderate to severe perianal skin reactions commonly occurred. Although the world experience of managing anal cancer in HIV infected individuals is small, this and other reports support the use of chemoradiotherapy in selected patients. The appropriate treatment of patients with more advanced tumours and/or advanced HIV infection is uncertain.

Recto-urethral fistula following brachytherapy for localized prostate cancer.

OBJECTIVE: The use of prostate brachytherapy (BT) in the management of prostate cancer is increasing. BT is often chosen because of its perceived lower toxicity when compared with other radical therapy options. Rarely however serious complications can occur. One such complication is recto-urethral fistula (RUF). We report the incidence of RUF following BT at our centre and review the potential factors in fistula development. METHOD: A prospectively collected database was used to identify cases of RUF among 1455 patients treated with prostate BT at a single UK centre with at least 2 years of follow up. This included patients treated with BT monotherapy, as well as those treated with BT combined with external beam radiotherapy and BT used as salvage as all these groups have a higher incidence of RUF. Implant dose and volume characteristics for those patients, their co-morbidities and history of endoscopic procedures were recorded. RESULTS: Recto-urethral fistula was identified in three (0.2%) patients, occurring at 19-27 months following BT. All these patients had BT monotherapy. All three patients had rectal symptoms after their BT and had been investigated with endoscopy and low rectal biopsy. Subsequent surgical management with faecal and/or urinary diversion was required. On review of patients' BT details, radiation dose and volume parameters were higher on the postprocedure CT calculations than had been suggested by the preimplant plan. No other predisposing risk factors for RUF were identified. CONCLUSION: The incidence of RUF in our population is low. RUF following BT has been associated with rectal biopsy in previous series and this is confirmed in our report. Gastrointestinal specialists should not perform biopsy of the anterior rectum in patients who have had BT unless there is a very high clinical suspicion of malignancy.

Prostate brachytherapy.

In recent years there has been an increase in the number of centres, especially in the USA, using prostate brachytherapy as a means of treating localised prostate cancer. Several centres now have medium term follow up data of large numbers of patients treated with this technique suggesting that outcome in terms of tumour control may be comparable to patients treated surgically. This review summarises results from different brachytherapy series and outlines some of the possible advantages of this technique compared with current conventional treatments for localised prostate cancer.

The infra-red coagulator in the treatment of AIDS-related Kaposi's sarcoma and a comparison with radiotherapy.

Experience with 1 s pulses of the infra-red coagulator is reported for the treatment of 10 cutaneous AIDS-related Kaposi's sarcoma lesions in seven patients. The infra-red coagulator may be a useful addition in the palliative cosmetic treatment of Kaposi's sarcoma, producing an acceptable result in small (less than 2 cm in diameter) Kaposi's sarcoma lesions of the arms and trunk, but not in those situated on the legs.

Short-term morbidity and acceptability of 125iodine implantation for localized carcinoma of the prostate.

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.