Материал: Oxford American Handbook of Urology ( PDFDrive )
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•Erectile dysfunction (ED) gradually develops in 30–50%.
•The risk of a second solid pelvic malignancy is estimated to be 1 in 300, falling to 1 in 70 long-term survivors.
Outcomes of EBRT
Definition of treatment failure
The traditional American Society of Therapeutic Radiation Oncologists (ASTRO) definition is 3 consecutive PSA increases measured 4 months apart for 2 years, thereafter every 6 months. Time to failure is midway through the 3 PSA measurements.
This has been recently updated to the so-called Phoenix definition PSA nadir + 2 ng/mL; the Phoenix definition is now preferred.1
Pretreatment prognostic factors
These include PSA, Gleason score, clinical stage, and percentage of positive biopsies.
5-year PSA failure-free survival
•85% for low risk (T1–2a or PSA <10 ng/mL or Gleason <7)
•50% for intermediate risk (T2b or PSA 10–20 or Gleason 7)
•33% for high risk without hormonal therapy (T2c or PSA >20 ng/mL or Gleason 8–10), improved with the use of neoadjuvant and adjuvant hormonal therapy
Treatment of PSA relapse post-EBRT
Hormone therapy, either as monotherapy or with antiandrogens, is currently the mainstay of treatment in this setting. However, local salvage treatment appears attractive, potentially offering another chance of cure if metastases cannot be demonstrated at repeat staging.
Salvage radical prostatectomy is technically demanding and can often be associated with poor outcomes; it appears best suited to younger patients in good health. Other local salvage treatments include cryotherapy and high-intensity focused ultrasound (HIFU), but outcomes data and access to these treatments are currently limited (see p. 230).
If salvage local treatment is being considered, repeat prostatic biopsies should be performed to demonstrate viable tumor cells. This should be at least 30 months post-EBRT, because fatally damaged cells may survive a few cell divisions. 1
1 Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H (2006). Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65(4):965–974.
228 CHAPTER 6 Urological neoplasia
Management of localized prostate cancer: brachytherapy (BT)
This is ultrasound-guided transperineal implantation of radioactive seeds, usually I125, less commonly Pd103, into the prostate. BT is minimally invasive, requires general anesthesia, and delivers up to 150 Gy. It is sometimes augmented by an EBRT boost.
Another approach is to use iridium192 wires, known as high-dose radiation (HDR), left for several hours in situ in a series of applications, either before or after EBRT. HDR is not widely available.
Indications for BT as monotherapy
BT is best for low-risk disease: localized T1–2a, Gleason <6, PSA <10 ng/ mL prostate cancer, with a life expectancy >5 years.
Indications for BT with EBRT
In the non-protocol setting, patients with intermediate-risk prostate cancer are sometimes treated in combination: T2b–T2c, Gleason 7, PSA 10–20 ng/mL.
Contraindications to BT
These include previous TURP (risk of incontinence); large-volume prostate (>60 mL), which causes difficulty with seed placement; and moderate to severe lower urinary tract symptoms (risk of retention).
High-risk prostate cancer does not do well with BT monotherapy and should not be performed.
Complications
•Perineal hematoma (occasional)
•Lower urinary tract symptoms (common), due to prostatic edema post-implant
•Urinary retention (5–20%)
•Incontinence (5%), if TURP is required to treat urinary retention
•ED affects up to 50% of patients; gradual onset
•Luteinizing hormone–releasing hormone (LHRH) analogue use to reduce prostatic volume prior to treatment is discouraged, as many men develop retention with this approach. A-Blockers are often used to treat LUTS.
Outcomes of BT
PSA rises in the first 3 months post-implant; it subsequently declines. As with EBRT, the ASTRO definition (see p. 227) has been used to define progression:
•5-year progression-free survival for T1 + 2a, Gleason d6, PSA <10 ng/ mL is 80–90%
•5-year progression-free survival for T2c, Gleason >6, PSA >10 ng/mL is 30–50%
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•8-year progression-free survival for T1 + 2a, Gleason <7, PSA <10 ng/mL is 79%
•12-year progression-free survival for T1 + 2a, Gleason <7, PSA <10 ng/mL is 66%
It is noteworthy that 50% of the patients in these published series had a normal PSA and Gleason score <5; these patients would have done well with watchful waiting. Patients with Gleason 8–10 do poorly after BT.
PSA progression continues steadily several years after treatment.
Outcomes of BT plus EBRT
Five-year progression-free survival is 75–95%.
Comparisons of BT or BT plus EBRT with RP and EBRT alone
•There are no randomized studies.
•In nonrandomized comparisons, an ageand tumor-matched radical prostatectomy series at 8 years yielded a progression-free survival of 98% (compared to 79% with BT).
•Outcome of BT appears inferior to that with EBRT and RP in men with
high-risk prostate cancer PSA >10–20 and Gleason score 7–10.
Rising PSA post-BT
Cryotherapy in an option if local recurrence is suspected; repeat staging and biopsy are indicated. Ultrasound images may be compromised in the setting of prior brachytherapy. Salvage prostatectomy can be considered in highly selected patients.
If metastatic disease is suspected or proven, hormone therapy is appropriate.
230 CHAPTER 6 Urological neoplasia
Management of localized and radiorecurrent prostate cancer: cryotherapy and HIFU
These two minimally invasive treatments for localized prostate cancer are in use in many locations. Proponents claim that they are viable alternatives to radical surgery or radiotherapy and that they are options for salvage treatment of organ-confined recurrent disease following radical radiotherapy.
Furthermore, there is growing interest in “focal therapy,” whereby only a portion of the prostate is treated, sparing side effects that may be associated with more aggressive treatments.
Proponents note that of all local therapies, these are the only two that can be repeated if there is a recurrence. Cryotherapy is widely available, whereas HIFU is not yet FDA approved in the United States.
Cryotherapy
A transperineal ultrasound-guided cryoprobe delivers argon or liquid nitrogen at a temperature of –20*C to –40*C. When applied in two cycles of freeze–thaw, cellular necrosis occurs. The diameter of the ice ball is monitored using ultrasound; precautions must be taken to protect the urethra, external sphincter, and rectal wall, such as using warming devices.
An anesthetic is required; this is a day-case procedure that can be repeated.
Results
PSA nadir is usually achieved within 3 months; 25–48% of men with localized disease achieve a PSA nadir of <0.1 ng/mL in 3 months, and 96% of men achieve PSA <0.2 ng/mL within 6 months. Positive biopsies are observed in 8–25% of patients after cryotherapy.
Long-term results are promising but appear inferior to other standard therapies and are not endorsed by the AUA in their 2007 treatment guidelines for localized disease.1
Complications
These include ED (40–80%); incontinence (4–27%); LUTS due to urethral sloughing; pelvic pain; transient penile numbness; and rectourethral fistula (rare).
In the salvage setting, good short-term PSA responses are reported in 66% of men, at the expense of significant morbidity, including incontinence and urinary retention (70% each).
High-intensity focused ultrasound (HIFU)
HIFU has the potential of selective destruction of tissues at depth without damaging intervening structures. Tissue is heated to the point of
1 Gleave M, Klotz L, Taneja SS. (2009). The continued debate: intermittent vs. Continuous hormonal ablation for metastatic prostate cancer. Urol Oncol. 27(1):81–86.
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coagulative necrosis by high-energy ultrasound transmitted to the prostate using a transrectal device. The tissue temperature is raised locally at this point (over 85°C).
With each firing of the probe, a cigar-shaped volume of damage is produced (a lesion). After one lesion is created, the focus is repositioned by computer guidance to create the next lesion with the same heating process. Lesions are placed side by side to create a continuous volume in which the tissue is necrosed. The rectal wall and the surrounding tissues are undamaged.
An anesthetic is required; this is a day-case procedure that can be repeated. The likelihood of morbidity is increased in the salvage treatment setting. Long-term results are awaited.
Complications
These include ED, urinary retention, stress incontinence, and recto-ure- thral fistula (rare).