The Impact of Prostate Size in Laparoscopic Radical Prostatectomy

The Impact of Prostate Size in Laparoscopic Radical Prostatectomy

European Urology European Urology 48 (2005) 285–290 Laparoscopy The Impact of Prostate Size in Laparoscopic Radical Prostatectomy C.M. Chang*, D. M...

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European Urology

European Urology 48 (2005) 285–290


The Impact of Prostate Size in Laparoscopic Radical Prostatectomy C.M. Chang*, D. Moon1, T.R. Gianduzzo1, C.G. Eden Department of Urology, The North Hampshire Hospital, Aldermaston Road, Basingstoke, Hampshire RG24 9NA, England, UK Accepted 26 April 2005 Available online 23 May 2005

Abstract Objectives: Large prostates can be challenging to remove during open or laparoscopic radical prostatectomy (LRP). Our objective was to critically analyse the impact of prostate volume in LRP. Methods: 400 cases of LRP were performed. Three hundred and fourteen patients had a small prostate (weight <75 g) and 86 patients had a large prostate (weight 75 g) on final histology. The following outcomes were assessed: operative time; estimated blood loss (EBL); transfusion rate; length of hospital stay (LOS); length of catheterisation; perioperative and postoperative complications (including incontinence and erectile dysfunction); surgical margin status; and early biochemical recurrence rates. Results: Patients’ age, PSA, Gleason sum and clinical stage were all similar. Larger prostates were associated with a 14 minutes longer mean operating time ( p < 0.001), but fewer positive surgical margins ( p = 0.01). Blood loss, blood transfusion rate, length of hospital stay, length of catheterisation and complication rate were all similar in both groups. Conclusions: Prostate size should not be a factor determining a patient’s suitability for LRP. Further follow-up is needed to assess the effect of prostate size on long-term functional and oncological results. # 2005 Published by Elsevier B.V. Keywords: Prostate cancer; Prostatectomy; Laparoscopic surgery

1. Introduction Over the last decade in the UK, radical prostatectomy has been an increasingly popular treatment for patients with localised prostate cancer [1]. Since the introduction of PSA testing, the volume of prostate glands removed for early stage cancer has increased substantially [2]. Patients with larger prostates are usually deemed unsuitable for external beam radiotherapy or brachytherapy and therefore require surgical intervention. Minimally invasive surgery utilising a laparoscopic approach for prostate cancer was first described by Schuessler et al [3] and in recent years

* Corresponding author. Tel. +44 1256 313532; Fax: +44 1256 313512. E-mail address: [email protected] (C.M. Chang). 1 Tyco Healthcare funds a fellowship in laparoscopic urology in our department. 0302-2838/$ – see front matter # 2005 Published by Elsevier B.V. doi:10.1016/j.eururo.2005.04.029

has become widely established [4–7]. Several studies have analysed the impact of prostate volume in open radical retropubic prostatectomy (ORP) [8–12]. In contrast, only one such study has been undertaken in laparoscopic radical prostatectomy (LRP) [13]. This recent study examined limited outcomes (operative time, blood loss and length of hospital stay) in 70 patients. Our aim was to critically analyse additional important outcomes after LRP with respect to prostate size.

2. Materials and methods 2.1. Patient selection and staging Between March 2000 and December 2004, four hundred appropriately-counselled and consenting patients with clinically localised adenocarcinoma of the prostate opting for surgery had LRP performed or supervised by a single surgeon (C.G.E.). Only one


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patient, who had recently undergone laparoscopic extraperitoneal pelvic lymph node dissection (PLND), was excluded from the initial phase of the series and underwent open surgery. All patients had a PSA 20 mg/l and a Gleason sum 8. Magnetic resonance imaging (MRI) was used for local staging in the first 17 patients but was subsequently abandoned after little correlation was found between MRI stage and final pathological stage. Patients were subsequently accepted for surgery on the basis of PSA (20 mg/l), Gleason sum (8) and DRE (clinical stage T3). Patients with a PSA >10 mg/l or a Gleason sum = 8 had a bone scan and computerised tomogram (CT) or MRI to exclude bone and lymphatic metastases. 2.2. Operative method and postoperative care Transperitoneal LRP (TLRP) was employed for the first 111 consecutive cases and extraperitoneal LRP (ELRP) was used in the remaining 289 consecutive patients as described previously [14].

Table 1 Patient demographics (values are mean plus range) Prostate 75 g

Prostate <75 g


n Age (years) Prostate size (g) PSA (mcg/l) Biopsy Gleason

86 64.2 98.2 8.5 6.0

314 61.4 46.7 7.5 6.1

– <0.001a <0.001a 0.04a 0.37a

Clinical stage T1 T2 T3

62 (73%) 22 (26%) 1 (1%)

151 (48%) 159 (51%) 4 (1%)

<0.001b <0.001b 0.94b

37 (43%)

84 (27%)


14 (16%)

47 (15%)


Preoperative erectile dysfunction Neoadjuvant hormonal manipulation a

2.3. Patient data and analysis Patients were divided into two groups depending on prostate weight on final histology (<75 g or 75 g). The following parameters in the two groups were compared: age; preoperative PSA value; clinical cancer stage; biopsy Gleason grade; preoperative erectile dysfunction; neoadjuvant hormonal manipulation; prior bladder neck incision or transurethral resection of the prostate; operative time; EBL; blood transfusion rate; hospital length of stay; length of catheterisation; intraoperative and perioperative complications; re-intervention rate; surgical margin status; biochemical recurrence; continence and erectile function. Operative time was measured from the time of skin incision to completion of wound closure. Biochemical recurrence was defined as a postoperative PSA of >0.2 mcg/l. Postoperative continence was defined as being pad-free. Bilateral nerve-sparing LRP was offered to patients <70 years of age, with a PSA <10, no primary Gleason grade 4 on biopsy, and no prior erectile dysfunction. Postoperative erectile function was reported by patients who had a nerve-sparing procedure at routine follow-up as the percentage of their preoperative strength of erection. Data on both postoperative continence and erectile function was prospectively collected and recorded by direct patient questioning at routine outpatient follow-up. Patient data was recorded using Microsoft Access XP software (Microsoft Corporation, Redmond, USA) and analysed using Microsoft Excel XP (Microsoft Corporation, Redmond, USA) and SPSS for Windows version 13.0 software (SPSS Inc, Chicago, Illinois, USA). A p value < 0.05 was considered statistically significant.


(52–75) (75–214) (3–19) (4–9)

(43–74) (14–74) (1–22) (4–10)

independent sample t test. chi-square test.

T1 prostate cancer ( p < 0.001), and conversely fewer patients with large prostates had clinical T2 prostate cancer than patients with small prostates ( p < 0.001). Biopsy Gleason score and preoperative neoadjuvant hormonal manipulation rate were similar in both groups. Operating time was a mean of 14 minutes longer in patients with large prostates ( p = 0.03). Patients with large prostates had a mean of 9.4% more PLND performed ( p = 0.055). Estimated blood loss, blood transfusion rate, postoperative hospitalisation and duration of catheterisation were similar in the two groups (Table 2). The single conversion to open surgery occurred in the eighth patient in the series at 300 minutes after dense posterior fibrosis prevented satisfactory progress. This patient did not have a large prostate. Most complications occurred in the early part of the series: three-quarters of the complications in the first 100 patients occurred in the first quarter of the series. The complication rate and early re-intervention rate was similar regardless of prostate size (Table 3).

3. Results Patient demographics are shown in Table 1. 86 patients had a prostate weight 75 g (range 75– 214 g, mean 98 g). 314 patients had a prostate weight <75 g (range 14–74 g, mean 47 g). Patients with small prostates were significantly younger than those with large prostates by a mean of 2.8 years ( p < 0.0001). Patients with large prostates had a 16% mean higher incidence of preoperative erectile dysfunction ( p = 0.004). The PSA of patients with a large prostate was higher by a mean of 1.0 mcg/l ( p = 0.04). Significantly more patients with large prostates had clinical

Table 2 In-patient results (values are mean plus range)

Prostate weight (g) Op. time (minutes) PLND Blood loss (ml) Blood transfusion Hosp. stay (nights) Catheterisation (days) a b

Prostate 75 g

Prostate <75 g


98.2 (75–214) 204 (117–315) 27.9% 276 (10–800) 1.0% 2.9 (2–8) 10.2 (1–35)

46.7 (14–74) 190 (100–540) 18.5% 257 (10–1300) 0% 3.1 (2–28) 11.0 (1–120)

<0.001a 0.03a 0.055b 0.45a 0.36b 0.38a 0.36a

independent sample t test. chi-square test.

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Table 3 Complications and re-intervention (values are numbers of patients) Prostate 75 g Complications Deep vein thrombosis (1) Pelvic haematoma (2) Lymphocoele (2) Submeatal stenosis (1) Suprapubic catheter (1)

7 (8.1%)a Early re-intervention Evacuation of pelvic haematoma (2)

2 (2.3%)b

Prostate <75 g Missed rectal injury and pelvic haematoma (1) Recognised rectal injury (2) Laparotomy for postop bleeding (1) Laparotomy for urinary peritonitis (1) Vesicorectal fistula (1) Bladder neck stenosis (4) Prolonged ileus (1) Ulnar nerve neuropraxia (1) 13 (4.1%)a Laparotomy and drain insertion (1) Laparotomy and haemostasis (1) Evacuation of pelvic haematoma (1) Formation of colostomy (1) 4 (1.3%)b

Early reinterventions are included in complications. a p = 0.13. b p = 0.48 (chi-square test).

The positive surgical margin rate was 10.5% for large prostates and 22.9% for small prostates and therefore was inversely related to prostate size ( p = 0.01). At a mean follow up of 8.2 (range 3–54) months in the small prostate group and 14.8 (3–42) Table 4

(a) Positive margins cT1 cT2 cT3 overall

Prostate 75 g

Prostate <75 g


3 (4.8%) 5 (22.7%) 1 (100%) 10.5%

30 (19.9%) 41 (25.8%) 1 (25%) 22.9%

0.005 0.76 0.82 0.01

(b) Biochemical recurrence (follow-up values are mean plus range) Biochemical recurrence 1.3% 5.7% 0.1 Follow-up (months) 14.8 (3–42) 8.2 (3–54) b

Fig. 2. Erection rates (p > 0.05 at all times, independent sample t test).

chi-square test.

Fig. 1. Pad-free rates (p > 0.05 at all times, chi-square test).

months in the large prostate group the biochemical recurrence rates were similar at 5.7% and 1.3% respectively (Table 4(b)). The pad-free rate in all patients increased with the length of follow-up and was not statistically influenced by prostate size at any time (Fig. 1). Erection rate also increased with time in all patients and was not statistically influenced by prostate size at any time (Fig. 2).

4. Discussion There is no consensus in the literature regarding the definition of what represents a large prostate. D’Amico et al found a significant difference between patients with prostate volumes above and below 75 cm3 with respect to organ-confined disease, surgical margin status, and PSA failure free survival after ORP [15]. Hsu et al. considered a prostate as being large when the volume was >72 cm3 since this volume was over the 90th percentile of the patient population in the study [12]. Similarly, Foley et al. used 75 g as the weight to differentiate between small and large prostates as this was the 90th percentile [11]. In our study, patients with prostate weights 75 g were compared to patients with prostate weights <75 g based on the categorisation of prostate size from these prior studies. We used pathological specimen weight as a measure of prostate volume. Good correlation has been shown between surgical specimen weight and transrectal ultrasound estimation of prostate volume [16]. The significantly higher mean age of patients with larger prostates (Table 1) merely reflects the association between ageing and increasing prostate size. Correspondingly, patients with larger prostates (who were also older) had a higher PSA. The proportion of men with preoperative erectile dysfunction (ED) was higher in men with large prostates (42%) than men with


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smaller prostates (27%). Again, patients with large prostates are tend to be older and therefore erectile dysfunction is more common. The proportion of patients with clinical stage T1 and T2 disease was higher in the large prostate group. Men with larger prostates have higher serum PSA levels due to the amount of benign hyperplastic prostate tissue [15], thereby prompting biopsies in which asymptomatic early-stage cancers are diagnosed [11]. The proportion of patients receiving neoadjuvant hormonal manipulation was similar in both groups and most of these patients had been started on this therapy by their referring urologist. Several technical issues during LRP on a large prostate gland may be encountered. The surgeon must always be alert to the possible presence of a large median lobe when performing LRP on a large gland. The plane between prostate and bladder-neck is no different to that seen in the small prostate, however the dissection may be made more difficult due to the poor elevation of the prostate by either a urethral sound or catheter. To overcome this problem, the authors use a laparoscopic Kocher via the right lateral port to grasp the median lobe and gain more elevation on the prostate in order to continue dissection along the posterior bladder-neck. Another issue is the wide gap between bladder and urethra that is left after removal of a large prostate resulting in tension on the anastomosis. Various manoeuvres may be performed to overcome excessive tension on the anastomosis including less Trendelenberg tilt, ensuring the midline balloon port is deflated completely, and further mobilisation of the bladder. No patient in our series required open conversion due to excessive tension on the anastomosis. Although the mean operating time was significantly longer in patients with large prostates, this was only by a margin of 14 minutes (Table 2). Patients in the large prostate group had a higher mean PSA, therefore were more likely to undergo PLND which prolonged the operative time. In the large prostate group 27.9% of patients had a PLND compared with 18.5% in the small prostate group and this was almost statistically significant ( p = 0.055). Two previous studies in LRP have also shown operative time to be significantly longer in patients with larger prostates [6,17]. The most recently published study in LRP by Singh et al [13] did not show a difference in operative times between patients with large or small prostates. However, this was a small study of 70 patients, and large prostates were defined as being over 50 g rather than 75 g. Operative times have been shown to be influenced by other factors such as surgeon experience, sural nerve grafting, pelvic lymph node dissection, and use of a surgical robot [17].

Hsu et al have previously reported a direct correlation between blood loss, transfusion requirement and prostate volume during ORP. Patients with larger prostates had a transfusion rate 2.5 times that of patients with smaller prostates [12]. Although blood loss per se is not a primary concern, blood loss requiring blood transfusion has negative implications for the patient such as cost, infection with blood-borne pathogens, transfusion reaction, and immune suppression. Blood loss is the most common intraoperative complication associated with ORP [18]. Even with improvements in surgical techniques, significant blood loss during ORP continues to be problematic [19]. Rassweiler et al noted a direct correlation of blood transfusion with prostate size in LRP: 17% of patients who had prostates <25 g required transfusions compared with 47% of patients who had prostates >45 g. Rassweiler et al admit that the ascending technique of dissecting the prostate is probably associated with a higher risk of bleeding [6]. Singh et al also reported a correlation of EBL with prostate size over 50 g which approached statistical significance [13]. The result may have been significant if the study had greater numbers and defined large prostates as those being >75 g. Contrary to these prior studies in ORP and LRP, we did not find that prostate size affected EBL or blood transfusion rate. LRP has the potential to significantly reduce surgical blood loss through a combination of venous tamponade by CO2 gas pressure, Trendelenburg tilt and perhaps also by more accurate dissection as a result of a better surgical view. The dimensions of the pelvic inlet are perhaps just as important operative variables as prostate size. A large, wide pelvis allows more operative movement and access to even a large prostate. Despite previous claims to the contrary [13], pelvic dimensions could be easily measured with a preoperative pelvic inlet X-ray. A ratio of pelvis size to prostate size could then be calculated and this ratio rather than prostate size alone may then correlate with operative outcomes after either ORP or LRP. Although this study did not examine this variable, it may be useful to pursue this issue in further studies to determine what factors impact upon outcomes in radical prostatectomy. Most complications occurred in the early part of the series: three-quarters of the complications in the first 100 patients occurred in the first quarter of the series. Most of the complications occurring in the initial phase of the series have not been repeated: urinary peritonitis due to poor anastomotic technique; ulnar nerve palsy due to a long operating time and inadequate padding of the arms; and ileus due to the use of a transperitoneal approach. Other complications, such as postoperative

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bleeding, have not been repeated but the potential for this will always exist and it remains an on-going challenge to minimise the risk of complications. There was no difference in overall complication rates for large or small prostates in our study (see Table 3). The positive margin rate correlated with clinical stage and was inversely related to prostate size in patients with clinical T1 disease (Table 4(a)). This is the only study examining this correlation in LRP, however similar findings have been reported in ORP [12]. A larger prostate is associated with both a lower initial biopsy rate and an increased number of subsequent biopsies driven by the PSA level [20,21]. This may result in the selection of smaller and more clinically indolent cancers in patients with larger prostates. Men with larger prostates have higher serum PSA levels due to the amount of benign hyperplastic prostate tissue [15] and thereby prompting biopsies in which asymptomatic early-stage cancers are diagnosed [11]. In the PSA era, men with stage T1c prostate cancers have larger prostates than stage T2 cancers [2] which would influence margin status in these larger prostates. Only the study by Foley et al in ORP did not show a difference in positive margin rates between small and large prostates. However it is difficult to draw a conclusion from this study when the positive margin rate for small and large prostates were 57% and 45% respectively. The positive margin rates in our LRP series are better than the ‘high standard for those advocating laparoscopic radical prostatectomy’ set by Lepor in his series of 1000 ORP [22]. The follow-up of 3 to 54 months for both groups is inadequate to make meaningful statements regarding biochemical recurrence, but the figures in Table 4(b) are comparable to the 9.5% biochemical recurrence rate in 1,000 patients undergoing LRP at a mean follow-up of 36 months [4]; the 11.0% biochemical recurrence rate in 1078 patients undergoing LRP at a mean follow-up of 20.8 months [23]; and the 7.0% biochemical recurrence rate in 1,870 patients undergoing ORP with a minimum follow-up of 18 months [24]. There are no other studies examining the impact of prostate size on biochemical recurrence in LRP, however previous studies in ORP have shown prostate size to be inversely related to PSA failure free survival. Stamey et al concluded that lead-time bias was the cause of the improved biochemical disease-free rates in men with larger prostates [25]. However, D’Amico et al. could not make this conclusion in all their patients and suggested a signalling mechanism that regulates benign epithelial cell proliferation in benign prostatic hyperplasia that may also act on coexistent cancer cells [15]. A lower positive margin rate for larger prostates


in our study may later also translate into a decrease in biochemical recurrence with longer follow up. Prostate size did not have a significant effect on return to continence (Fig. 1). This is the only study in LRP looking at this relationship, although other studies confirm the same finding in ORP [8–12]. Continence in ORP has been reported to depend on other factors such as patient age, the surgical technique used, and experience of the surgeon [8–10]. At each postoperative follow-up appointment, patients in our study were questioned about the number of pads used by them per day. A validated questionnaire for continence was not used, which is a limitation of our study. Prostate size did not appear to affect return to preoperative potency (Fig. 2). Walsh and Donker suggested that a smaller prostate might lessen the likelihood of damage to the nerves of the pelvic plexus [26]. On the other hand, in a larger prostate the neurovascular bundles are displaced posteriorly and may be obscured by the prostate making them prone to injury [27]. Our results do not support these claims, although again our study is limited by direct patient questioning at follow-up appointments rather than the use of a validated sexual function questionnaire. The significant incidence of postoperative erectile dysfunction seen after radical prostatectomy, even in centres of excellence, is an indication that there is still much to learn about the anatomy and mechanism of erections and how to minimise the surgical impact in radical prostatectomy. It has been suggested that 50 procedures are necessary to satisfy the learning curve. The proficiency to perform LRP in 4 hours ranges from 15 to 60 cases [28,29]. The impact of the learning curve on the results of this study is not possible to define. Except for a single patient early in the series who had had a recent PLND, all patients who presented for surgical treatment of localised prostate cancer were accepted for LRP regardless of factors such as prostate size. In the first 50 cases in our series, only 2 cases had a prostate size >75 g (case number 40 was 82 g, and case number 50 was 76 g). The various outcome parameters for these 2 patients were no different than those for the other 48 patients in the first 50 cases (data not shown).

5. Conclusions Our series represents a comprehensive assessment of the impact of prostate size on outcomes after LRP. Operative times for patients with large prostates were 14 minutes longer than patients with small prostates. In LRP, prostate size did not have an impact on outcomes such as EBL, blood transfusion rate, LOS, length of


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catheterisation, complications (including postoperative incontinence and erectile dysfunction), or early biochemical recurrence rates. A lower incidence of positive surgical margins was observed in patients with larger prostates. Longer follow up is needed to confirm

if a lower positive margin rate in larger prostates translates into a biochemical free survival benefit. With the trend towards larger prostates undergoing LRP, these patients can be reassured of excellent outcomes following laparoscopic surgery.

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