Radical retropubic prostatectomy: A review of outcomes and side-effects

Abstract

Background. Radical prostatectomy (RP) is worldwide probably the most common procedure to treat localized prostate cancer (PC). Due to a more widespread use of Prostate-Specific Antigen (PSA) testing, patients operated today are often younger and have organ confined disease justifying a more preservative surgery. At the same time, surgical technique has improved resulting in lower risk of permanent side-effects. This paper aims to give an overview of results from modern surgery regarding cancer control and side-effects. A brief overview of the history is given. Material and Methods. A literature research identified recently published papers focusing on outcome and side-effects after RP. Results. One large randomized study (SPCG-4) compared RP and watchful waiting (WW). The study showed that RP was superior to WW in preventing local progression (RR = 0.36), distant metastasis (RR = 0.65) and death from PC (RR = 0.65). Observational studies also show a better outcome for men treated with RP compared to WW. Peri-operative mortality after RP is low in most material around 0.1%. The risk of stricture of the vesico-urethral anastomosis has decreased with improved technique from historically 10–20% to a low incidence of around 2–9% today. Also the risk of incontinence has declined with improved technique. However, while the rates of severe incontinence is usually very low, as many as 30% still report light incontinence after long-term follow-up. Erectile dysfunction (ED) is still a frequent side-effect after RP. This risk is dependent on age, pre-operative sexual function, surgical technique and other risk factors for ED such as smoking, diabetes, etc. In selected subgroups the risk of ED is low. Inguinal hernia is a more recently described complication after open retropubic RP with a postoperative incidence of 15–20% within three years of surgery. Conclusion. RP is an effective method to achieve cancer control in selected patients. With modern technique it is a safe procedure with a low risk of permanent side-effects except for ED.

Prostate cancer (PC) is a major public health problem. It is one of the most commonly diagnosed cancers and one of the most common causes of cancer-related death in developed countries [1,2]. The estimated incidence of PC in the USA was nearly 192 280 new cases in 2009 [1] and 345 900 new cases in Europe in 2006 [3]. From being a rare disease in the 19^th century, the incidence has increased rapidly during the past century, especially during the last two decades. A man's lifetime risk of a PC diagnosis has more than doubled from 8% in the early 1980s to almost 18% today [4]. The discovery of the Prostate-Specific Antigen (PSA) test in the 1970s [5–7] is likely to explain most of this increase, reflected in that the greatest increase in incidence constitutes of non-palpable tumors. Screening with digital rectal exam and/or the PSA test offers detection of early stage, clinically localized and potentially curable disease. These tumors can be managed in different ways, however, radical prostatectomy (RP) is today considered gold standard for treating localized PC [8,9]. The frequency of curative treatment for early-stage disease with surgery as primary treatment has increased and evolved enormously since the late 1980s [10–14]. Though providing an effective means of treating localized disease [14], feared side-effects of RP are urinary incontinence and impotency. The surgeon's technique put priorities on cancer control, continence and potency [15]. The main indication of RP is patients with low- and intermediate- risk localized PC (cT1a-T2b and Gleason score 2–7 and PSA ≤20) and a life expectancy >10 years [9]. However, treating high grade as well as locally advanced tumors have also been reported with favorable outcome [16].

The aim of the present paper was to give an overview of results from modern surgery regarding cancer control and permanent side-effects. A brief overview of the history is given. The study did not intend to compare different ways of performing RP or RP with other treatment modalities.

Material and methods

A literature research through April 5, 2011 identified recently published papers focusing on outcome and side-effects after RP. Medical electronic databases were used (MEDLINE as well as the Cochrane Library to identify systematic reviews). Information was also derived from guidelines. Keywords for the literature search included: radical prostatectomy, surgical technique, mortality, side-effects, impotence, incontinence and inguinal hernia. Data extraction and quality assessment were made by the authors.

Results

History

Billroth performed the first perineal prostatectomy for palliation of obstructive PC in the 1860s [17] followed by Young in the beginning of the 20^th century [18]. In the early 1930s the procedure was replaced by transurethral prostatic resection for this indication [19]. The first retropubic prostatectomy was performed by Millin in 1945 [20]. However, many of the tumors were detected late. The discovery of the PSA changed this and prostatectomy could be regarded as a means of treating early disease. In the early 1980s, Walsh described in detail the anatomy of the prostate, the dorsal venous complex and the neuro-vascular bundles [21] and he also performed the first nerve-sparing radical retropubic prostatectomy (RRP) [22]. These efforts led to improvements in postoperative continence and potency as well as reducing peroperative mortality [22]. Peroperative blood loss is aimed at being minimized and the known postoperative complications may be reduced to low levels in expert hands [23]. Modifications and improvements of surgery, anesthesia and pre- and postoperative care have been made throughout the years, with a decrease in complication rates [24]. RP can be performed either as open retropubic surgery, laparoscopic surgery, robotic-assisted laparoscopic surgery as well as perineal surgery. Evidence is lacking which technique is superior as regards oncological and functional results as well as cost-effectiveness [9]. Observational studies have compared different modalities [25], but no randomized controlled trial exists to date. A large Swedish study (LAPPRO) is currently ongoing comparing open retropubic prostatectomy with robotic-assisted laparoscopic prostatectomy [26].

Outcome

The three primary outcomes of RP, cancer control, continence and potency, are achieved to a high extent today. RP is associated with excellent cancer control in men with organ confined disease up to 10 years of follow-up [27]. Prostate cancer-specific survival in localized disease has been reported to be 86–99.6% at 10 years [9,28–30], 82–90% at 15 years [31,32] and 76% at 30 years [33].

The benefits of RP as compared to expectant management have been reported in one large prospective randomized trial (SPCG-4) judged to be of good quality [34]. This Scandinavian landmark study, reported by Holmberg et al., randomized (in 1989–1999) 695 men with clinical stage T1-2 tumors to either watchful waiting or RP. During a median of 10.8 years of follow-up, RP significantly reduced the risk of local progression (RR = 0.36), the risks of metastasized disease (RR = 0.65) and disease-specific mortality (RR = 0.65, 95% CI 0.45–0.94; p = 0.03) [14]. There was a statistically significant difference in overall mortality rates for men <65 years randomly assigned to RP as compared to watchful waiting (RR 0.59, 95% CI 0.41–0.85, p = 0.004) [14]. However, the number needed to treat (NNT) to “cure” a single case of PC with RP was calculated to 10–19. This rather high NNT could be explained by a high risk of over-treatment (treating too many indolent cancers) or treating too advanced cancers where local treatment no longer is effective. The latter explanation is supported by the fact that in the SPCG-4 trial, the majority of prostate cancers were palpable tumors. However, there is no doubt that also in the SPCG-4-trial there is a high rate of overtreatment emphasizing the demand for a very low rate of permanent side-effects to justify RP in these men. There are three major clinical trials (PIVOT, ProtecT and START) ongoing that investigate the outcomes of RP vs. expectant management for PSA-detected tumors.

Observational studies

In a cohort study of men aged 55–74 years with non-metastasized disease diagnosed during 1971–1984, RP was compared with external beam therapy and observation. Kaplan–Meier estimates for 10-year disease-specific and overall survival were in favor of RP (86% for disease-specific survival, 95% CI 84–88% and 69% for overall survival, 95% CI 67–71%) [29].

In another observational cohort study (including 44 630 men aged 65 to 80 years) of men with low and intermediate risk localized PC, the adjusted hazard ratio for overall mortality comparing RP with observation was 0.50 (95% CI 0.47–0.53) [35].

The natural history of today's prostate cancers that are often PSA-detected is not completely understood. Stattin et al. reported 10-year outcomes of men in the National Prostate Cancer Register of Sweden Follow-up Study that included men aged ≤70 years at diagnosis, local tumor stage T1-2, Nx or N0, Mx or M0, and PSA <20 ng/ml. For men with low-risk PC, the cumulative 10-year PC-specific mortality was 2.4% (95% CI 1.2–4.1%) among men on conservative management and 0.4% (95% CI 0.13–0.97%) among men who underwent RP [30].

However, non-randomized studies have limitations and should be interpreted with caution because of the risk of selection bias and comparison between treatment modalities is beyond the scope of this review.

Side-effects

Short-term side-effects. Thirty-day mortality. We performed a nationwide population-based record-linkage study in which the 30-day mortality after RP was low, 0.11–0.13% [36], a finding consistent with previous studies based on modern series [31,37–43]. Co-morbidity [44] and increasing age are factors associated with higher risk of perioperative death [41,45–46]. Hospital volume and surgeon volume may also affect the outcome [37,44]. As indicated by our study group [36] and others, ischemic heart disease and pulmonary embolism still seems to constitute the majority of causes of deaths following RP [47–50].

Long-term side-effects. All treatments for PC at different stages have side-effects. The most well-known and bothersome postoperative complications after RRP are urinary incontinence, impotence and stricture of the vesico-urethral anastomosis [51,52]. Large improvements in surgical technique have been made during the past three decades and the risk of side-effects has fallen and together with the earlier detection of PC this results in RP today being a procedure with much lower morbidity [28]. However, while at the same time earlier detection provides a higher chance of cure and treatment with less side-effects, it also implies a higher risk for over-treatment and, in the case of permanent side-effects that still can follow, a long-time suffering for the individual. Due to inconsistency in reporting the outcomes in the literature, the incidence of post prostatectomy urinary incontinence ranges from 0% to 87% [53–57] and postoperative potency rates vary from 11% to 87% [53]. It has been shown that sexual function can continue to improve even beyond two years postoperatively [58,59]. At 52 months after RP, 88% have been reported to suffer from erectile dysfunction and 31% from urinary leakage [60].

However, it should be noted that already before surgery, the prevalence of erectile dysfunction is high in population-based studies. Long et al. have reported that 64% suffered from erectile dysfunction overall pre-operatively; 43% of patients younger than 65 and 84% of patients over 65 [61]. Salonia et al. showed that only 43% of 234 men with localized PC candidates for bilateral nerve-sparing RP had a normal erectile function pre-operatively [62].

Risk factors for postoperative impotence include non-nerve sparing surgery, the surgeon's ability to master the technique, age of the patient, baseline sexual function, and risk factors for erectile dysfunction including diabetes, hypertension and smoking [63].

The average incidence of severe incontinence is, in most studies, not greater than 5% [55,64], however, severe urinary leakage has a huge negative impact on a patient's quality of life.

The risk of stricture of the vesico-urethral anastomosis has decreased with improved technique from historically 10–20% [65] to a low incidence at around 2–9% today [9].

Quality of Life. Studies have shown that men reported similar (or indicated even better) quality of life after RP compared to men assigned to watchful waiting [52,66]. Better mental health scores and health-related-quality of life scores for men having undergone RP has also been reported compared with men having undergone radiotherapy [66] as well as compared with a control group of men without cancer [67].

Inguinal hernia. Inguinal hernia (IH) as a postoperative complication to RP is less well known and was first reported by Regan et al. in 1996 [68]. Later reports indicate an incidence of IH of 12% to 21% within two to three years after RRP [69–74]. The background annual incidence of inguinal hernia is approximately 0.5% [75]. These results have recently been confirmed from the SPCG-4 study, a prospective randomized study between RRP and watchful waiting with a follow-up of over 12 years [14], where 9.3% developed IH after RRP within 48 months as compared to 2.4% in a group of non-operated men with PC and 0.9% in a population control group [76]. Today IH can definitely be considered a complication to RRP.

The lower mid-line incision per se has been suggested to be causative [69–74]. In a study from 2008, Koie et al. reported a postoperative IH incidence of only 2.9% in a group of 272 patients where RRP was performed through a so called “mini- laparotomy” incision of only 6 cm [77]. Matsubara et al. also reported an IH incidence of 1.8% after radical-perineal prostatectomy where the whole procedure is performed through a perineal incision and consequently there is no abdominal incision at all [78]. In a recent study of 946 patients after robot-assisted laparoscopic radical prostatectomy (RALP) 5.8% developed an IH within 48 months as compared to 12.2% after RRP. There was no statistical difference in IH incidence after RALP as compared to a population control. Thus, the length, and possibly the placing, of the abdominal incision seems to affect the development of postoperative IH [76].

Concluding remarks

It is 150 years since the first RP was performed. Enormous improvements in surgical technique have been achieved especially during the last 20 years. It is nowadays a safe procedure with excellent cancer control in men with localized disease and few side-effects apart from ED. The main challenge in the future is to further decrease the risk of sexual dysfunction and to avoid over-treatment.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.