Материал: Oxford American Handbook of Urology ( PDFDrive )

222 CHAPTER 6 Urological neoplasia

Postoperative course after radical prostatectomy

Patients are generally hospitalized for 24–48 hours and maintain Foley catheter drainage for 10–14 days. The robotically assisted laparoscopic prostatectomy (RALP) is associated with reduced blood loss and more rapid discharge from the hospital. Currently, there are no convincing data that the long-term functional and oncological outcomes are improved by the less invasive robotically assisted laparoscopic approach.

Complications of radical prostatectomy

General complications

These include those of any major surgery: bleeding requiring reoperation and/or transfusion; infection; thromboembolism; and cardiopulmonary complications or disturbance. These are minimized by attention to hemostasis, prophylactic antimicrobials, pneumatic calf compression, low-dose heparin postoperatively, and early mobilization.

Specific complications—early

Intraoperative obturator nerve, ureteral, or rectal injury (all rare) should be managed immediately if recognized, with end-to-end nerve anastomosis; ureteral reimplantation; or primary three-layer rectal closure with or without a temporary loop colostomy.

Postoperative catheter displacement (rare) is managed with careful replacement using cystoscopic guidance over a wire if there are any concerns over the integrity of the anastamosis. If beyond 3–5 days postoperatively, a urethrogram may reveal no leak and the catheter may not need be replaced.

Postoperative urine or lymphatic leak (distinguished by fluid creatinine concentration) through drains (occasional) is managed by prolonged catheter and wound drainage; lymphatic leaks may require sclerotherapy with tetracycline.

Lymphocele (encapsulated collection of lymphatic fluid) can cause lower extremity swelling or abdominal discomfort. It is unusual with the RALP as the peritoneum is usually opened. Lymphocele can be sclerosed or drained intraperitoneally by a laparoscopic approach.

Specific complications—late

Erectile dysfunction (ED) affects >50% of patients who were potent preoperatively; spontaneous erections may return up to 3 years postoperatively. Men >65 years or with pre-existing ED are more likely to suffer long term.

From 40% to 70% respond to oral PDE5 inhibitors at 6 months, while others require intraurethral or intracavernosal prostaglandin E1 treatments, a vacuum device, or (rarely) a prosthesis. Penile rehabilitation protocols (immediate use of PDE5 inhibitors, vacuum devices, or prostaglandins) may enhance the return of spontaneous erectile function.

POSTOPERATIVE COURSE AFTER RADICAL PROSTATECTOMY 223

Incontinence (stress-type) requiring >1 pad/day affects 5% of patients beyond 6 months and is due to injury of the external urethral sphincter during division and hemostatic control of the dorsal vein complex. The predisposing factors include age >65 years and excessive intraoperative blood loss.

Pelvic floor exercises (Kegel exercises) and the use of biofeedback techniques can help the return of continence. Periurethral bulking injections or implantation of an artificial urinary sphincter are occasionally necessary.

The use of male urethral slings has gained popularity. Incontinence may also develop secondary to bladder neck stenosis or detrusor instability; flow rates, post-void residual measurement, urodynamics, and cystoscopy may help.

Bladder neck stenosis (bladder neck contracture) affects 5–8% of patients and typically occurs 2–6 months postoperatively, rarely becoming a recurrent problem. Predisposing factors include heavy bleeding, postoperative urinary leak, and previous TURP.

Patients complain of new voiding difficulties, and treatment is by endoscopic bladder neck incision with a laser, cold knife, or electrocautery. Occasionally, chronic dilation may be necessary.

224 CHAPTER 6 Urological neoplasia

Prostate cancer control with radical prostatectomy

While there are no randomized studies comparing RP outcomes to those of radiotherapy, a randomized study comparing RP to watchful waiting has demonstrated a 40% reduction in death due to prostate cancer and a significant reduction in local and metastatic progression in the RP group with a mean follow-up of 8.2 years.1 High-grade cancers were excluded from this trial, though nonrandomized data suggest that more patients with Gleason 7–10 localized disease survive 10 years following RP than with watchful waiting or radiotherapy.

Excellent long-term results are seen in well-selected patients following RP, particularly those with organ-confined disease and prior lower urinary tract symptoms from bladder outflow obstruction. Serum PSA is usually measured at least 6–12 weeks postoperatively, then every 6 months; it should fall to <0.2 ng/mL.

The 10-year PSA progression rate following RP (usually defined as a serum PSA >0.2 ng/mL) is about 2–30%. Of these, the majority will fail within 3 years of RP. Without additional treatment, the time to development of clinical disease after PSA progression averages 8 years.2

A 20-year clinical disease-free survival of 60% is reported.3 Outcome following radical prostatectomy correlates with Gleason score; preoperative PSA; pathological T stage; and surgical margin status.

Progression-free probabilities are shown in Table 6.5.

Neoadjuvant hormone therapy given 3 or more months prior to RP does not alter the PSA progression rate, despite reducing the incidence of positive surgical margins, and is not routinely used.

Two large studies have demonstrated that adjuvant radiation therapy in the setting of adverse pathology can greatly reduce the rate of PSA progression following radical prostatectomy. SWOG 8794 demonstrated a 50% reduction in PSA recurrence in patients with positive surgical margins who received adjuvant radiation therapy.4

Similarly, in EORTC 22911, adjuvant RT improved progression-free survival from 74% to 52.6%.5 Neither study has yet demonstrated an absolute survival advantage.

1 Holmberg L, et al. (2002). A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 347:781–789. An update has been published: BillAxelson A, Holmberg L, Ruutu M, et al. (2005). Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 352:1977–1984.

2 Pound CR, Partin AW, Eisenberger MA, et al. (1999). Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281:1591–1597.

3 Swanson GP, Riggs MW, Earle JD (2002). Long-term follow-up of radical retropublic prostatectomy for prostate cancer. Eur Urol 42:212–216.

4 Swanson GP, Hussey MA, Tangen CM, et al. (2007). Predominant treatment failure in postprostatectomy patients is local: analysis of patterns of treatment failure in SWOG 8794. J Clin Oncol. 25(16):2225–2229.

5 Bolla M, Van Poppel H, Collette L (2007). Preliminary results for EORTC trial 22911: radical prostatectomy followed by postoperative radiotherapy in prostate cancers with a high risk of progression. Cancer Radiother 11(6–7):363–369.

PROSTATE CANCER CONTROL WITH RADICAL PROSTATECTOMY 225

Table 6.5 Progression-free and metastasis-free survival after open retropubic RP without adjuvant therapy, probability (%)

* 3+4 = 7 fares better than 4+3 = 7.

† Only 40–50% of patients with a positive surgical margin after RP develop a rising PSA

Management of biochemical relapse post-RP

The definition of PSA recurrence following RP is generally agreed to be a PSA of >0.3 ng/mL and rising. DRE should be performed in case there is a nodule. Biopsy of the vesicourethral anastomosis is not widely practiced unless there is a palpable abnormality.

Studies have shown that MRI and bone scans are rarely helpful in searching for metastatic disease unless the PSA is >7 ng/mL.

Current management options include observation, pelvic radiotherapy, or hormone therapy. A good response to pelvic radiotherapy is likely with the following:

•Positive surgical margins at the time of the RP

•PSA rise is delayed >1 year

•PSA doubles in >10 months

•PSA is <1 ng/mL at the initiation of radiation

•The original disease was low grade and low stage

•The radiation dose exceeds 64 Gy

If the PSA never falls below 0.2 or it rises in the first year with a doubling time of <10 months, the response to pelvic radiotherapy is less effective. It is likely in these circumstances that micrometastatic disease is present, and some form of androgen ablation therapy is usually recommended.

226 CHAPTER 6 Urological neoplasia

Management of localized prostate cancer: radical external beam radiotherapy (EBRT)

Advances in radiotherapy for localized prostate cancer have included the development of conformal and intensity-modulated techniques to minimize toxicity to the rectum and bladder. EBRT is administered with curative intent, often accompanied by neoadjuvant and adjuvant hormone therapy in high-risk disease.

In general, 2–3 years of hormonal therapy are given for high-risk disease, usually starting before the initiation of radiation therapy. While some data suggest that a shorter course of hormonal therapy (i.e., 6 months) may suffice for intermediate-stage disease, it is not considered standard. There is no role for adding hormonal therapy in low-risk disease.

Hypofractionation (delivery of a total dose of radiation but in a shorter time frame (i.e., 5 days) by use of various stereotactic body radiotherapy (SBRT) platforms has been promoted. Hypofractionation is currently not considered a standard treatment and is under study by groups such as the Radiation Therapy Oncology Group (RTOG).

Proton beam therapy (in contrast to photons used in standard radiation) is a very costly radiation technique that is gaining interest as more centers adopt this technology. The promise is that the side-effect profile may be improved using protons over standard radiation. The role of proton therapy remains to be determined.

Indications

These are clinically localized prostate cancer and life expectancy >5 years. Patients with Gleason score 2–4 disease appear to do as well with watchful waiting as with any other treatment, with 15-year follow-up.

Contraindications

•Severe lower urinary tract symptoms

•Inflammatory bowel disease

•Previous pelvic irradiation

Protocol

EBRT involves a 6- to 7-week course of daily treatments amounting to a dose of 60–72 Gy. Some centers use higher doses of radiation (up to 80 Gy) in an attempt to improve disease control.

Side effects

The use of contemporary radiation techniques that limit the exposure of normal tissues has greatly reduced the complication rates.

•Transient moderate/severe filling-type LUTS (common, rarely permanent)

•Hematuria, significant: 4%

•Moderate to severe gastrointestinal symptoms, bloody diarrhea, pain: 3–32% (common, rarely permanent)