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The role of palliative surgery in castration-resistant prostate cancer

Piper, Charlotte; Porres, Daniel; Pfister, David; Heidenreich, Axel

Current Opinion in Supportive and Palliative Care: September 2014 - Volume 8 - Issue 3 - p 250–257
doi: 10.1097/SPC.0000000000000078
RENAL AND UROLOGICAL PROBLEMS: Edited by Fred Saad
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Purpose of review Androgen deprivation therapy with luteinising hormone releasing hormone (LHRH) analogues or antagonists represents the treatment of choice in men metastatic prostate cancer (PCA). Depending on the serum concentration of the prostate-specific antigen (PSA) nadir, the survival might vary between 11 and 78 months. About one-third of all patients without local treatment of the primary will develop significant complications of the lower and upper urinary tract because of local progression of PCA. It is the purpose of the review to inform the treating physician about palliative surgical options in men with castration-resistant prostate cancer (CRPC).

Recent findings In men with CRPC and lower urinary tract symptoms, palliative transurethral resection of the prostate (TUR-P) can be performed with a 60–70% success rate. Infiltration of the pelvic floor, the bladder neck and trigone and the external urethral sphincter can make palliative radical surgery necessary. Bladder neck closure with continent vesicostomy, radical cystoprostatectomy with an incontinent urinary diversion, and anterior and posterior exenteration are individual therapeutic options in men with a good performance status and a considerable life expectancy. Symptomatic involvement of the upper urinary tract can be managed by placement of endoluminal stents or a percutaneous nephrostomy in men with a poor performance. In men with a good response to androgen deprivation therapy (ADT) and a good performance status reconstructive ureteral surgery might be considered and the options of ureteral reimplantation, ureter ileal replacement and a subcutaneous pyelovesical bypass have to be discussed.

Summary There are various palliative surgical treatment options in the management of men with CRPC and symptomatic deterioration of the lower or the upper urinary tract, which should be considered in well selected patients. The indication to perform one of the above-mentioned surgical approaches needs to be discussed in a multidisciplinary tumour board.

Department of Urology, RWTH Uniklinik Aachen, Aachen, Germany

Correspondence to Dr Axel Heidenreich, Professor, Chairman and Director, Department of Urology, RWTH Uniklinik Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. Tel: +49 241 8089374; fax: +49 241 808 2441; e-mail: aheidenreich@ukaachen.de

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INTRODUCTION

Prostate cancer (PCA) is the most common malignant tumour and the reason for the third most tumour-associated death in men [1▪▪] with PCA has been diagnosed worldwide and about 50% of those men will develop metastatic disease within the 5–10 years of follow-up and approximately 10–20% of those will develop castration-resistant prostate cancer (CRPC) within 5 years of follow-up [2].

Androgen deprivation therapy (ADT) with luteinising hormone releasing hormone (LHRH) analogues/antagonists represents the guideline-recommended treatment of choice for PCA with skeletal metastases [1▪▪]. The M1 population, however, comprises a very heterogeneous group of patients with survival times, which vary between 11 and 75 months [3–5,6▪]. An updated more precise classification of the SWOG8894 trial has been published, which discriminates patients into three groups according to survival, with a median overall survival of 54, 30 and 21 months, respectively [4]. The prospective randomized SWOG 9346 trial compared the oncological efficacy of intermittent versus continuous ADT in a cohort of 1078 M1 PCA patients [5]. After controlling for prognostic factors, the amount of prostate-specific antigen decrease stratified patients into three risk groups, which exhibit statistically significant differences in overall survival. The median survival was 13, 44 and 75 months in men with PSA serum levels higher than 4 ng/ml, higher than 0.2 ng/ml and less than 0.2 ng/ml respectively.

Eighty-four percent of men with CRPC exhibit metastases at time of diagnosis of CRPC and another 5% will develop metastatic disease within 2 years after diagnosis of CRPC [2]. Until recently, the median survival after diagnosis of CRPC was 14 months only. However, owing to the development of new drugs and the various sequencing options of immunomodulatory, endocrine and cytotoxic manipulations, median survival can achieve a time frame ranging from 20 to about 80 months in good responders [1▪▪]. Owing to this considerably long life expectancy even in men with CRPC, we might be faced with a higher frequency of complications of the lower and upper urinary tract because of progression of the prostate itself, local recurrences and/or pelvic or retroperitoneal lymph node metastases. More than one-third of all patients without local treatment of the primary will develop significant complications of the urinary tract because of local progression of PCA [6▪,7].

Complications might include subvesical obstruction, recurrent gross hematuria with or without clotting, upper urinary tract dilatation, rectourethral or rectovesical fistulae and rectal obstruction. Besides the involvement of the urinary tract, the skeleton represents another organ system, which is prone to complication such as bone pain, pathologic fractures or spinal cord compression/infiltration. In their final year of life, 46% of patients with CRPC experienced PCA-related symptoms and 25% of the patients needed surgical interventions.

In addition to the clinical studies, it has been shown recently that systemic treatment will not result in complete eradication of intraprostatic vital and lethal cancer cell clones, which might give rise to local progression and systemic metastases. Tzelepi et al.[8▪▪] analyzed the outcome of a well selected cohort of high-risk PCA with lymph node metastases who were treated with docetaxel chemotherapy and 1 year of androgen deprivation therapy before they underwent radical prostatectomy and pelvic lymphadenectomy. Despite the extensive pretreatment, all radical prostatectomy specimens contained vital cancer cells with biologically lethal properties as assessed by immunohistochemistry of various biomarkers implicated in disease progression and therapy resistance. These data at least raise the suspicion that persisting intraprostatic cancer foci may be involved in local progression and development of systemic metastases [9–12].

Apparently, all new medical treatment options can induce complete and partial remissions in metastatic foci, but they have no profound effect on the prostate itself. Therefore, it seems to be necessary to develop palliative surgical strategies to relief patients from symptoms and thereby to improve quality of life.

The current review article focuses on surgical options in the management of patients with CRPC and symptomatic involvement of the upper or lower urinary tract.

Box 1

Box 1

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LOWER URINARY TRACT

The frequency of symptomatic lower urinary tract involvement in CRPC depends on the primary treatment as has been shown by various groups [6▪,9–13]. Radical prostatectomy significantly reduced the incidence of local complications compared with that of patients who did not undergo local surgical therapy (20 versus 54.3%, P = 0.001) or who did undergo external beam radiation therapy (EBRT) (20 versus 46.7%, P = 0.007 [6▪]). The risk of local complications was not reduced significantly in patients who underwent EBRT as compared with those with no local treatment (46.7 versus 54.6%). Bladder outlet obstruction developed in 4.4, 35.6 and 42.8% of patients who underwent RP, EBRT or no local treatment, respectively. Similar results were reported by Steinberg et al.[9] who described a risk of local progression requiring surgical intervention in 3, 43 and 46% of men with CRPC who underwent RP, EBRT or no local treatment. Various other groups described a significantly increased local control rates in men with m PCA who underwent RP and ADT as compared with those who were only subjected to ADT alone [10–13].

Symptomatic local recurrences after radical prostatectomy might develop at the anastomotic site, at the resection site of the vas deferens or at remnants of the seminal vesicles left behind despite radical prostatectomy.

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PALLIATIVE TRANSURETHRAL RESECTION OF THE PROSTATE

Palliative transurethral resection of the prostate (TURP) represents the surgical treatment of choice in men subvesical obstruction and/or recurrent gross haematuria because of locally recurrent CRPC with or without bladder neck infiltration who are not candidates for a radical surgical approach such as salvage radical prostatectomy [13–16]. It is still discussed controversially whether palliative TURP might lead to an accelerated frequency of systemic metastases due to the intraoperative tumour cell shedding, which could result in an increased prostate cancer mortality rate during follow-up.

Various groups have described a therapeutic success rate of 70–90% in terms of deobstructing the bladder outlet, prevention of recurrent bleeding and bladder clotting [13–16]. About 10% of the patients will need surgical reinterventions because of local recurrences during follow-up. Another 10–15% will remain on a transurethral or suprapubic catheter because of recurrent subvesical obstruction or surgery-related incontinence. If performed properly, palliative TURP is not associated with a higher frequency of surgery-related complications as compared with standard TURP for the management of benign prostate hyperplasia.

In our own series of 83 patients with CRPC who underwent palliative TURP, the mean resection weight was 13 (5–39) g and 15% developed postoperative complications with the need of reinterventions: acute urinary retention in two, bladder clotting in three, permanent suprapubic catheter in three, Re-TURP in three and urinary incontinence in two patients. The perioperative mortality was 0% and after a mean follow-up of 3.6 years, 32.5% had died because of PCA.

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PALLIATIVE RADICAL PROSTATECTOMY

In case of an infiltration of the pelvic floor or the external urethral sphincter, a wide distal resection of the prostate is mandatory, which would result in urinary stress incontinence with significant impairment of quality of life. In order to combine both adequate resection of CRPC and maintenance of continence, we adapted the surgical technique of continent vesicostomy with the use of either the appendix or a small ileal segment [17]. To achieve a good functional outcome postoperatively, the bladder capacity should be at least 300 ml and no involvement of the upper urinary tract should be present. Following RP, the bladder neck is closed by a two-layer running suture. If present, the appendix is isolated with its mesenterial blood supply and the tip of the appendix is resected [18]. The bladder is opened and a wide submucosal tunnel is created through which the appendicular tip is advanced in the bladder and fixed by single sutures. The oral part of the appendix is implanted in the lower right abdominal quarter or it is connected with the umbilicus to serve as catheterizable stoma. In case of a previously performed appendectomy, the Montie procedure is used to create an efferent stoma; one or multiple ileal segments of 5–10 cm in length are resected and opened antimesenterically [19]. The opposite edges of the ileal segment are sutured together over a 14-F catheter to create a long efferent nipple, which is implanted in the bladder as described above. Our own experience comprises 31 patients. The mean surgical time was 125 (100–195) minutes and we did not observe significant intraoperative or perioperative Clavien grade 3–5 complications. The mean follow-up is 37 (10–78) months and only two cases developed a stenosis at the level of the fascia of the rectus abdominal muscle. The remainder did not develop complications and is continent. This procedure can also be used to treat recurrent bladder neck strictures after radical prostatectomy [17,20].

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PALLIATIVE RADICAL (CYSTO-)PROSTATECTOMY

In some patients, local progression of CRPC can result in bladder neck infiltration or infiltration of the dorsal bladder with or without involvement of the ureters. In some cases, significant pelvic pain might result from local extension in the small pelvis. To avoid placement of suprapubic tubes, endoluminal stents or percutaneous nephrostomy tubes, radical (cysto-)prostatectomy and urinary diversion might be indicated in well selected patients [21–23]. Indications for open palliative surgery of the lower urinary tract are as follows:

  1. Eastern Cooperative Oncology Group (ECOG) performance status 0–1
  2. Charlson comorbidity score 10 or lesser
  3. ASA status 2 or lesser
  4. Life expectancy more than 1 year
  5. Absence of pelvic infiltration (MRI mandatory)
  6. Recurrent gross hematuria with the need for repetitive blood transfusions
  7. Recurrent bladder clotting
  8. Persisting and significant pelvic pain not manageable by pain therapy

Selection criteria include: ECOG performance status 0–1; a still well circumscribed mass on preoperative MRI studies, which makes a complete resection feasible; absence of bulky lymph node disease interfering with a careful ureterolysis, which is mandatory to achieve a well vascularized ureteroileal anastomosis; absence of significant comorbidities as indicated by a Charlson comorbidity score 9 or higher; rectosigmoidoscopy and transrectal ultrasound to rule out infiltration of the rectum. In case of documented infiltration, the patient must be informed about the need of rectal resection and the placement of a permanent colostomy.

If the selection criteria are respected, palliative radical cancer surgery can be performed with a low rate of complications and good palliative results. However, the surgery itself is a challenging procedure and it should only be performed in very experienced hands to avoid outing harm on the patient (Fig. 1a–e). Owing to our extensive experience in SRP for radiotherapy failures of prostate cancer and in postchemotherapy retroperitoneal lymphadenectomy, we feel very comfortable to performing extensive radical cancer surgery in those patients [24,25]. Palliative radical cystoprostatectomy was performed in 40 patients so far and no significant Clavien grade 3–5 complications were observed, whereas five (12.5%) patients developed complications such as lymphoceles, intrapelvic abscess and paralytic ileus so that the complication rate of the palliative procedure resembles the experiences of radical cystectomy in bladder cancer [21]. The mean surgical time was 260 (150–430) minutes and the mean blood loss was 560 (400–1000) ml. The mean time of hospitalization was 14 (10–23) days. The mean survival time of our patient cohort was 20.4 (1–28) months and most importantly, the mean symptom-free survival was 15.3 (1–25) months covering 75% of the total survival time. These data are in line with the results of other groups [22,23].

FIGURE 1

FIGURE 1

Symptomatic rectal infiltration makes an anterior and posterior pelvic exenteration necessary. The necessity for a permanent colostomy and an ileal conduit resulting in two external drainage systems has to be discussed with the patient and his family preoperatively.

With regard to urinary diversion, we prefer an ileal conduit or even a simple ureterocutaneostomy in selected cases over a continent urinary diversion, as surgery usually is faster, complication rates are lower, postoperative recovery is quicker and a large proportion of patients already demonstrates an involvement of the upper urinary tract with an impairment of renal function. If ureterocutaneostomy is performed, we prefer a surgical technique allowing one external drainage system for both ureters [26,27]. The left ureter is pulled to the right side retrosigmoidally; both ureters are spatulated allowing a side-to-side anastomosis of the ventral and the dorsal aspect of the right and the left ureter. The tube-like common ureter is pulled through the stoma and fixed to the skin by everting sutures similar to an ileal conduit. The outcome of patients is equivalent to minimally invasive procedure such as double-J stents or percutaneous nephrostomy tubes but without the need for regular replacements of the systems (see below).

In summary, palliative radical surgery is a challenging but feasible local treatment option in well selected patients if performed in experienced hands. Definitively, palliative radical (cysto-)prostatectomy should be considered more often in the management of men with locally progressing, symptomatic CRPC (indications for open palliative surgery of the lower urinary tract as described above).

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URETERAL OBSTRUCTION

About 5–15% of men with CRPC experience symptomatic or asymptomatic ureteral obstruction. Prior to any endourological, percutaneous or surgical procedure, treatment must be individualized and risk stratification is of paramount importance [28–32]. A profound decision-making analysis is especially important in patients with an asymptomatic dilatation of the upper urinary tract and a well functioning contralateral kidney. The potential life expectancy, comorbidities and the wish of the patient and his family have to be taken into consideration. Especially in the clinical scenario of minimally invasive procedures such as placement of double-J stents or percutaneous nephrostomy tubes, the decision needs to be made carefully because placement of the devices usually is performed easily, but stent infection, encrustation and blockages are common problems, which are difficult to manage and which significantly interfere with the patient's quality of life [30]. New compression-resistant metallic stents seem promising for patients with a malignant disease who require long-term urinary drainage [28,29]. However, even with metallic and self-expandable ureteric stents, the main complications remain in about 25–30% of patients: stent migrations, urinary tract infections and blockage of stents.

Endourological or percutaneous procedures (double-J stent, PCN) are indicated in men with symptomatic obstruction, impaired renal function and a short life expectancy contraindicating reconstructive surgical procedures. If to choose, double-J stents should be preferred because of the internal drainage, the significantly longer changing intervals as compared with PCN (4–6 months versus 6 weeks) and the less interference with daily life activities. In case the classical transurethral retrograde, implantation is not possible because of a significant obstruction of the ureter; antegrade placement after percutaneous puncture of the lower renal calyceal system might be more successful.

Percutaneous nephrostomy is well tolerated and effective in relieving ureteral obstruction and reasonable survival can be achieved even in patients with renal failure [30–32]. About 75% of the patients who present with severe renal failure will experience an adequate return of renal function [31,32]. The 1-year and 2-year survival rates depend strongly on the presence of hormone sensitive or castration-resistant PCA. In men with androgen-sensitive PCA, 1-year and 2-year survival rates are 73 and 47%, whereas the numbers decrease to 48 and 19% in men with CRPC [31,32]. The median survival time of the total cohort of patients with PCA and obstruction of the upper urinary tract is expected to be around 2 years so that urinary diversions are strongly recommended in those patients. However, one has to consider that PCNs are associated with a total complication rate of approximately 65% including the development of arteriovenous fistulas and gross hematuria requiring additional interventions such as transfusion of red blood cells and superselective embolization [30–32].

When the conservative measures have failed, the performance status of the patient is good and the life expectancy is considerably long, supravesical reconstruction and diversion may be an option and the following treatment options need to be discussed and considered [33,34]: ureteroneocystostomy, ureteral ileal replacement and placement of a percutaneous pyelovesical bypass (Detour system).

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URETERONEOCYSTOTOMY

Unilateral or bilateral ureteral reimplantation might be discussed as an alternative to endoluminal stents or percutaneous nephrostomy in patients with a distal obstruction of the ureter towing to PCA infiltration of the trigone and the ureteral orifices. In some patients, distal ureteral resection and reimplantation might also be considered if obstructive uropathy is due to lymph node metastases occluding the ureter in the small pelvis [34]. Patients should exhibit an ECOG performance status 0–1 and a life expectancy of at least 1 year. Indications for open palliative surgery of the upper urinary tract are as follows:

  1. ECOG performance status 0–1
  2. Charlson comorbidity score 10 or lesser
  3. ASA status 2 or lesser
  4. Life expectancy more than 1 year
  5. Symptomatic obstruction of the upper urinary tract
  6. Significant renal impairment
  7. Bladder capacity more than 300 ml
  8. Absence of subvesical obstruction

They also should have a normal bladder capacity of about 300–400 ml, no evidence of subvesical obstruction and normal micturition characteristics. Ureteral reimplantation is performed as described for benign ureteral stricture disease except that we do not prefer the Psoas Hitch technique to prevent secondary obstruction because of future lymph node involvement in the area of the external and/or common iliac artery. In the clinical scenario of palliative surgery, we favour an implantation technique usually used in renal transplantation procedures in which the ureter is implanted at the bladder dome. Postoperatively, a transurethral catheter is left in place for 5 days and the endoluminal stent is left in place for about 2 weeks. Frequency of intraoperative and perioperative complications is in the range of 5% and they usually comprise minor Clavien grade 2–3 complications. If the above-mentioned surgical technique of ureteral implantation is respected, long-term outcome is good with more than 90% of the ureteral implants remaining patent without recurrent obstruction. If the classical Psoas Hitch technique is used, 20–40% of patients develop local complications during a mean survival time of about 2 years.

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SUBCUTANEOUS PYELOVESICAL BYPASS (DETOUR SYSTEM)

The subcutaneous pyelovesical bypass has been introduced recently as a minimally invasive surgical procedure to treat ureteral obstruction for malignant ureteral obstruction in patients with considerable, but still limited life expectancy. This new device can be applied for the bypass of any ureteral obstruction located between the renal pelvis and the urinary independent on its extent and cause [35–37].

The average follow-up of the reported patient cohorts is in the range of 2 years (range 1–92 months). The quality of life was significantly improved as indicated by the analysis of EORTC QLQ-C30 questionnaires. Intraoperative complications are minimal and those should be expected to occur in about 10% of patients. Postoperative urinary tract infections and wound complications were encountered in about 15% of the patients. In the long-term run, about 10% of the patients might develop infections of the detour system, which might be cured by the intravenous application of antibiotics or the explantation of the system in the presence of severe complications. Limited patient numbers and lack of long-term data represent the only drawbacks of this technology.

The Detour system consists of two parts: the inner silicone stent with a diameter of 24F and the outer Gortex coat. Placement of the Detour system has to be performed under general anaesthesia with the patient in the supine position. Prerequisites are basically identical to those for patients who are candidates for ureteral reimplantation (indications for open palliative surgery of the upper urinary tract as described above). In brief, to place the cranial tip of the device, the lower calyx of the dilated collecting system is punctured under ultrasound guidance. The puncture canal is dilated to 27F under fluoroscopy allowing the placement of an Amplatz shaft, which enables the placement of the cranial tip of the Detour system in the renal pelvis (Fig. 2a). To allow an easy implantation at the bladder site, a small vertical lower abdominal mini laparotomy of about 4 cm is performed, the Spatium Retzii is explored and the bladder is opened between two stay sutures. Using a specific tunnelling instrument, a subcutaneous tunnel is created bluntly between the flank incision and the urinary bladder so that the prosthesis can be advanced through the hollow tunnelling instrument (Fig. 2b). The silicone tip is inserted into the bladder and the Goretex tip is fixed to the bladder wall with 4–6 single sutures (Fig. 2c, d). Five days postoperatively, patency of both the bladder and the Detour system is proven via cystography and an excretory urography (Fig. 2e).

FIGURE 2

FIGURE 2

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SUMMARY AND CONCLUSION

Palliative surgery of the lower and the upper urinary tract will become more important in the future because of the availability of new medical treatment options such as abiraterone acetate, enzalutamide, cabazitaxel and radium-223 significantly prolonging survival. For unknown reasons, medical treatment induces objective remissions in metastatic deposits. However, it exerts only minor responses of the prostate if still in place. Palliative surgery to the prostate includes transurethral resection of the prostate, radical prostatectomy or radical cystoprostatectomy with urinary diversion and even anterior and posterior exenteration in well selected patients. If performed properly, patients will survive 75% of their remaining life time without symptoms because of local progression of the prostate. Symptomatic involvement of the upper urinary tract might necessitate the placement of endoluminal double-J stents or percutaneous nephrostomy in men with a poor performance status and a short life expectancy. In men with an ECOG performance status of 0–1, reconstructive surgery including ureteral reimplantation, ureter ileal replacement or placement of a subcutaneous pyelovesical bypass represents a feasible treatment option. The indication to perform one of the above-mentioned surgical approaches needs to be discussed in a multidisciplinary tumour board. Both the urologist and the medical oncologist need to be well informed about the surgical palliative treatment options in men with CRPC.

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Acknowledgements

None.

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Conflicts of interest

The authors do not have any conflicts of interest to declare.

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REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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Keywords:

castration-resistant prostate cancer; continent vesicostomy; detour system; radical cystectomy; radical prostatectomy; subcutaneous pyelovesical bypass; ureteral reimplantation

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