The clinical assessment establishes whether the patient is a suitable candidate for prostate brachytherapy and confirms their disease stage and risk group. Relevant features in the medical history include anticoagulant use, diuretic therapy, diabetes, inflammatory bowel disease, connective tissue disorders, previous diagnosis of pelvic cancer (especially bladder or rectum), prior pelvic radiotherapy and radiation sensitivity syndromes such as ataxia telangiectasia. Important urologic history would include prior transurethral or open resection of the prostate, urethral surgery, procedures for benign prostatic hyperplasia such as transurethral needle ablation or microwave therapy, medications for urinary symptoms and prior erectile dysfunction. Prior pelvic surgery or the presence of a total hip replacement would be relevant features of the surgical history. Information about the patient’s baseline urinary, erectile and bowel function may be obtained from self-administered validated questionnaires such as the International Prostate Symptom Score (IPSS), the International Index of Erectile Function (IIEF) and the EORTC QLQ/PR-25 questionnaire [11–13]. During the outpatient consultation, the clinical T stage is evaluated by digital rectal examination. Uroflowmetry may be carried out in the outpatient clinic to assess the Q_max (maximum urinary flow rate) and voided volume. The post-void residual volume may be measured by transabdominal bladder ultrasound and should be less than 200 cm³ for patients being considered for brachytherapy [14]. Transrectal ultrasound may be performed in the clinic to visualise the prostate gland. This can demonstrate median lobe hyperplasia, an existing TURP defect, eccentric BPH (which may displace the urethra from the midline) or the presence of intra-prostatic calcification (which creates artefact on the TRUS imaging used to guide seed implantation).

The authors consider undertaking cystoscopy and bladder neck resection in patients with small prostates (<40 cm³) who have obstructive urinary symptoms or signs, together with median lobe hyperplasia, to attempt to reduce urinary obstruction in the long term. Figures 43.2 and 43.3 show the bladder neck at cystoscopy before and after resection.

The maximal cross-section of the prostate gland should be carefully compared to the anterior-posterior space between the pubic arch and the ultrasound probe to avoid the phenomenon of pubic arch interference during the eventual seed implant. This occurs when the pubic arch blocks the passage of the introducing needles into the anterior and antero-lateral prostate [15]. This tends to affect large prostates (>60 cm³) but may also depend on pelvic anatomy, patient position and implant technique.

According to the updated American Brachytherapy Society (ABS) guidelines for TRUS-guided permanent prostate brachytherapy [14], absolute contraindications to brachytherapy include:

Co-morbid conditions that pose unacceptable surgical or anaesthetic risks should be considered. Active prostatitis and active inflammatory bowel disease may be considered relative contraindications [19], although there are small series of patients with a history of inflammatory bowel disease who have tolerated brachytherapy well [19–21]. Patients who have received prior pelvic radiotherapy need to be carefully assessed for symptoms and signs of late radiation toxicity to the pelvic organs, and may require evaluation with sigmoidoscopy and cystoscopy. The dose previously delivered to the prostate, rectum and bladder should be estimated from the details of their previous radiation therapy. Advanced age is not considered a contraindication to brachytherapy. Obesity may not be a contraindication provided the patient has an acceptable performance status and life expectancy, and can be supported by the operating theatre apparatus.

The presence of pre-treatment obstructive urinary symptoms is predictive of the development of acute urinary retention post-operatively [22]. This may be indicated by an International Prostate Symptom Score (IPSS) greater than 15 or a post-void residual volume of greater than 200 cm³. Patients with an IPSS of 8 or less have a low risk of developing acute retention and prolonged urethritis post-operatively [14]. Pre-implant IPSS correlates with the duration of post-implant obstructive symptoms but is not a predictor of long-term urinary quality of life [23, 24]. The pre-implant maximum urine flow rate, Q_max, and the presence of prostate median lobe hyperplasia are both predictive of post-implant acute urinary retention [12, 25, 26]. It is recommended that patients selected for brachytherapy should have Q_max greater than 15 ml/s [17].

The biological criteria of pre-treatment PSA, prostate biopsy Gleason score and clinical T stage are used to stratify patients with localised prostate adenocarcinoma into low-, intermediate- and high-risk groups. Several risk classifications exist, each based on the same three risk factors.

Patients presenting with high-risk disease or more than one intermediate-risk factors should be staged with an isotope bone scan and CT or MRI of the abdomen and pelvis [14]. The ABS favours the National Comprehensive Cancer Network (NCCN) classification (Table 43.2).

The risk of subclinical extracapsular extension (ECE) is reflected by the risk group classifications. Patients in the low risk group may be suitable for treatment with LDR seed implantation alone (monotherapy). Some practitioners select patients from the intermediate risk group for monotherapy and others use a combination of EBRT and brachytherapy. The ABS recommend combined EBRT and LDR implantation in patients with initial PSA >20 ng/ml or Gleason score 8–10 and T2b-T2c disease. The authors consider seminal vesicle invasion to be a contraindication to LDR brachytherapy. Such cases may be considered for neoadjuvant and adjuvant ADT with EBRT, with or without an HDR brachytherapy boost.

Prior TURP used to be considered a contraindication to LDR brachytherapy, due to rates of urinary incontinence as high as 17 % in early series in the 1990s, but this is no longer the case. With careful pre-operative assessment of the TUR defect, incontinence among selected patients treated with brachytherapy after TURP may be avoided. The seed implant should be delayed until 2–4 months after TURP to allow healing [14].

Pubic arch interference with large prostates (>60 cm³ in volume) may be overcome by a period of 3–4 months of ADT, which may downsize the prostate volume by about 30 %. For more modest-sized glands, placing the patient in an exaggerated lithotomy position and re-aligning the TRUS probe in a horizontal rather than angled-down position may overcome pubic arch interference.

Prostate LDR brachytherapy alone (monotherapy) is recommended for low-risk disease (see Table 43.2 for risk group definitions). Published series demonstrate that excellent long-term clinical outcomes can be obtained in this patient group provided adequate dosimetric parameters are achieved [14, 27–29]. ADT may be useful for downsizing the prostate gland [30–33]. The authors consider combining ADT with LDR brachytherapy in patients with a high burden of disease (i.e. all biopsies cores involved with Gleason 3 + 3 disease) due to the increased risk of occult extracapsular extension and metastasis.

Patients in the intermediate-risk group are more likely to harbour adverse pathological features such as extracapsular extension, seminal vesicle invasion and lymph node metastasis than patients in the low-risk group. Pathological series have demonstrated that extracapsular extension of prostate cancer rarely extends beyond 5 mm in patients with clinically organ-confined disease [34, 35]. This region of potential extracapsular extension is covered by most good quality brachytherapy implants due to the typical margin of 5 mm added around the prostate to generate the Planning Target Volume and the fact that the radiation dose distribution extending several millimetres beyond the prescription isodose is often adequate to treat microscopic disease [36–38].

Patients with low-volume disease, a predominant Gleason score 3 pattern and a single adverse factor for intermediate-risk disease may be treated with monotherapy [14, 39]. Among the remaining patients in the intermediate-risk group, the optimum therapeutic strategy is controversial. A pattern-of-care study among brachytherapists with a combined experience of more than 10,000 patients identified additional factors such as proportion of positive biopsy cores and the presence of perineural invasion which practitioners consider with T-stage, initial PSA and Gleason score when trying to decide whether to treat intermediate-risk cases with monotherapy or in combination with EBRT and ADT [39].

Patients with high-risk disease have a substantial chance of subclinical ECE beyond the range of a permanent prostate brachytherapy implant. This was reflected in the poor results of monotherapy for this group in early brachytherapy series [29]. It has become standard practice to combine an LDR brachytherapy implant with EBRT for this reason. Retrospective series suggest that escalating radiation dose by combining EBRT and a LDR brachytherapy implant improves local control of prostate cancer and metastasis-free survival.

Large randomised prospective trials of EBRT dose escalation for high-risk locally advanced prostate cancer with 3-dimensional conformal radiotherapy (3D-CRT) and, more recently, intensity modulated radiotherapy (IMRT), have confirmed improvements in disease control [40–42]. Combining EBRT with LDR brachytherapy aims to deliver greater dose escalation to the prostate and any surrounding subclinical ECE.

The use of neoadjuvant and adjuvant ADT with primary EBRT is supported by randomised prospective evidence [43, 44]. Although the use of ADT with combined EBRT and LDR brachytherapy for high-risk disease is popular, the evidence that it produces improved clinical outcomes is limited [17]. Delivering a greater biologically effective dose in patients with Gleason score 8–10 disease was shown to improve overall and metastasis-free survival in a large multi-institutional series [45].

At centres using a two-stage technique, the patient attends for the volume study and the seed implantation is performed on a later occasion [48]. The treatment planning is completed in the meantime and the required seeds are ordered. It can be difficult to accurately replicate the patient position from the volume study and internal pelvic organ motion may cause some variation.

Single-stage techniques, where dosimetry is calculated just before or during the implant procedure, are increasingly popular due to the flexibility of planning and need for just one anaesthetic. They were popularised by Stock and Stone [49]. The ABS subcategorises intraoperative planning techniques into: intraoperative preplanning, interactive planning and dynamic dose calculation.

Intraoperative preplanning involves performing a TRUS in the operating room and importing the 3-dimensional ultrasound data into the treatment planning system on a computer in the room. The target volume and organs at risk are contoured on the treatment planning system and the prostate is implanted according to plan generated.

Interactive planning involves real-time feedback of needle positions to the treatment planning system via image guidance so that the plan can be recalculated after each needle position is adjusted. Dynamic dose calculation uses feedback of 3-dimensional seed position to continuously recalculate the dose distribution throughout the procedure. Being able to re-plan the treatment intraoperatively gives a further opportunity to optimise the treatment plan compared to preplanned techniques.

Two of the authors have developed a versatile real-time one-stage technique (“4D-Brachytherapy”) which avoids seed migration by using a combination of preloaded stranded seeds around the periphery of the prostate and loose seeds loaded with a Mick applicator [46]. An institutional nomogram has been developed from over 1,000 brachytherapy cases to enable the appropriate combination of stranded and loose seeds to be ordered based on the measurements of the prostate from a TRUS in the outpatient clinic. The technique has shortened the time taken for planning and implantation to around 40 min. Changing from the 2-stage Seattle technique to 4D-Brachytherapy has resulted in a significant improvement in prostate D₉₀ and V₁₀₀ doses [46]. Acute urinary morbidity and erectile function have also improved significantly (with potency rates 2 years post-implant improving from 61.7 to 83.3 % and use of phosphodiesterase-5 inhibitor medication falling from 53.3 to 31.7 %).

Cystoscopy may be required to remove misplaced seeds or blood clots from the bladder but is not performed routinely if bladder irrigation is clear and there is no radiological evidence of seeds within the bladder. Techniques employing loose seeds have a rate of seed migration as high as 15 %. Examples of seed migration to the chest, abdomen and pelvis have been documented, including a case of a non-smoker developing a limited stage small-cell lung cancer [61–64].

Irritative and obstructive urinary symptoms are the most common acute side effects of prostate LDR brachytherapy. Patients may be offered a 2–3 month course of an α-blocker post-implant, prophylactically. In many cases, exacerbation of urinary symptoms resolves within 2–3 months of the implant. The authors published a study of 100 patients treated with LDR brachytherapy, which found that acute urinary symptoms peaked at 6 weeks post-implant and that a statistically significant decrease of IPSS score persisted until 9 months post-implant [12]. Seven patients in this study developed acute urinary retention, but the mean IPSS score 2 years post-implant was improved. In one study of 712 consecutive patients treated with LDR brachytherapy, resolution of IPSS (defined as the post-implant IPSS returning to within 2 points of the pre-implant score) occurred in 85.3 % of patients [65]. A questionnaire study of 174 patients with over 5 years follow up after LDR brachytherapy reported good or acceptable quality life due to urinary symptoms (an IPSS quality of life score of 0–4) among 98 % of respondents [66].