In 2009, prostate cancer affected an estimated 192,280 men with a median age at diagnosis of 68 years [1
]. It represents 71% of all pelvic tumors in men. According to a review of the SEER database, 37% of prostate cancer patients are treated with RT within 6 months of diagnosis [2
], with 26% receiving EBRT and 15% BT. The treatments are delivered alone or in combination. Historically, the dose delivered to the prostate by conventional EBRT was 60–68 Gy with the dose-limiting factor being toxicity to adjacent organs, namely the bladder and the rectum. Through increased target specificity, 3D-CRT and IMRT may now allow safe delivery of radiation doses to the prostate in the range of 78–84 Gy [9
]. Permanent seed implants (LDR-BT) typically deliver 125–145 Gy to the prostate.
The benefits of RT for prostate cancer are well documented in literature. Thompson et al. showed that men randomized to receive adjuvant EBRT for locally advanced prostate cancer after prostatectomy experienced improved metastasis-free survival as well as overall survival [12
]. Cohort series suggest 10-year cancer control outcomes for low- and intermediate-risk prostate cancer are similar regardless of whether men are treated with surgery, EBRT or BT [13
]. For this reason, the AEs of therapy are an important consideration in selecting primary therapy for prostate cancer.
Urinary AEs following EBRT for prostate cancer are varied. In general, the incidence of persistent grade 1 symptoms (>90 days after RT) is reported to be 20–43% with a follow-up of up to 10 years [16
]. The incidence of late grade 2 AEs is reported to be 7–19% [16
]. However, these symptoms continue to accrue with time: the actuarial risk of genitourinary AEs of grade 2 or greater was 15% following 3D-CRT at 3 years and 19% by 5 years [18
]. Of those who develop mild to moderate AEs, many appear to resolve, either spontaneously or with treatment. In a study by Zelefsky et al. 64% of patients with late grade 2 urinary toxicity following 3D-CRT had subsequent resolution or significant improvement of their symptoms within 42 months [17
Grade 3 urinary AEs occur in 5–13% after EBRT [19
]. Like grade 2 AEs, grade 3 AEs continue to accrue with long follow-up. Indeed, in one EBRT trial, grade 3 urinary AEs occurred in 5–7% at 31 months and 12–13% at 51 months [19
]. Hemorrhagic cystitis is the most common grade 3 complication of prostate RT. Grade 3 and 4 hematuria was reported in 8.7% of patients with onset up to 10 years following RT [22
]. Advances in EBRT technology are intended to increase the specificity of radiation and minimize adjacent organ damage. However, radiation oncologists have used this as an opportunity to increase the delivered dose, resulting in better tumoricidal activity but also increased damage to the target organ. Although dose escalation with IMRT lowered rectal toxicity, it actually increased the urinary toxicity [11
]. The urethra may not be spared any better with IMRT than with conventional EBRT.
Late grade 2 AEs following BT affect 19–41% of the patients and most commonly include hematuria and obstructive or irritative urinary symptoms [23
]. Urethral strictures (grade 3) following BT occur in 1–12% of men; risk is increased by combination therapy with EBRT and is related to the dose delivered to the apex of the prostate [25
]. With short follow-up, grade 4 urinary AEs (life-threatening hematuria or necrotic/contracted bladder) appear to be rare (<1%) after BT or EBRT [11
]; however, with extended follow-up, the rate increases to 2% after EBRT or 3.3% after BT+EBRT [19
]. A SEER-Medicare examination showed that within 2 years of BT, 10% had a procedure performed for a urinary AE [25
]. Risk factors included older age, non-white race, low income, co-morbidities, combination therapy with EBRT or hormonal therapy and history of prior transurethral resection of the prostate.