SEARCH

SEARCH BY CITATION

Keywords:

  • transitional cell carcinoma;
  • percutaneous surgery;
  • ureteroscopy

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

In this Issue, there are four mini-reviews, three of which relate to cancer of the genitourinary system. In the first of these the endourological management of upper tract TCC is described by authors from the Mayo Clinic who have a long-term experience in this area. The second and third of the mini-reviews concern prostate cancer, but in different ways. The authors from Sacramento write about the use of the artificial urinary sphincter for post-prostatectomy incontinence. Obviously this includes surgery for benign disease also, but the main emphasis is on its use after radical prostatectomy for prostate cancer. The other article is about the use of ErbB receptors as possible therapeutic targets, from the University of Leicester. Finally in this section, authors from Kingston, Ontario, have written a mini-review on hypogonadism and erectile dysfunction, relating pathophysiology to treatment and outcomes.


Abbreviations
CIS

carcinoma in situ.

INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

TCC has a 2–5% incidence of upper urinary tract involvement and accounts for 5–10% of renal tumours [1,2]. The standard treatment for upper tract TCC remains nephroureterectomy, but endourological techniques are increasingly used for definitive therapy [3–7]. The interest in endoscopic treatments has accompanied endourological advances like narrower ureteroscopes and laser development. Ureteroscopic and percutaneous approaches to upper tract TCC are safe and give encouraging results. We discuss the rationale, clinical approach and outcomes associated with the endourological treatment of upper tract TCC.

RATIONALE

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

Conservative therapy is traditionally reserved for patients with solitary kidneys, bilateral disease or renal insufficiency. Endoscopy provides results equivalent to conservative open surgery and the advantages of minimally invasive surgery [4–6]. Similar to conservative open surgery, endoscopy avoids the mortality associated with dialysis. For example, in a contemporary series of 128 unselected haemodialysis patients (mean age 61 years) the 3-year survival rate was 55%[8]. In addition, patients with comorbidity precluding nephroureterectomy or conservative open surgery can also benefit from endoscopic treatment. For instance, endoscopic therapy has been used for patients with significant cardiopulmonary disease when general anaesthesia was contraindicated [4,5].

Endourological therapies are used increasingly for patients with normal contralateral kidneys [5,9]. Just as cystectomy is not required for many patients with superficial TCC, selected patients with low-grade upper tract lesions may not require nephroureterectomy [5,6,9]. For instance, a low incidence of invasiveness and metastasis is associated with low-grade upper tract tumours [6,10,11]. In addition, most nephroureterectomies have characteristically been for lesions ultimately found to have a low grade and stage [6]. As such, many patients may be candidates for endoscopic treatment, as opposed to nephroureterectomy. Nonetheless, endourological treatment for patients with normal contralateral kidneys remains controversial. We recommend elective treatment only for completely resectable, small (< 2.0 cm), solitary, low-grade tumours [4,5]. Furthermore, patients must accept postoperative surveillance protocols and the possibility of tumour recurrence.

PREOPERATIVE EVALUATION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

The careful selection of patients is required for successful endourological therapy. Haematuria most commonly accompanies upper tract TCC; symptoms like flank pain are rare. Upper tract lesions are also detected during the surveillance of patients with bladder cancer. Previous bladder cancer has been recorded in 15–84% of patients with upper tract tumours [1,4,5,7,12]. For example, Elliott et al.[4] reported that 15 of 21 patients with renal pelvic tumours and 22 of 23 with ureteric TCC undergoing endourological treatment had a history of bladder cancer.

Upper tract TCC is traditionally evaluated with excretory urography, retrograde pyelography and urine cytology. CT increases the sensitivity for differentiating filling defects to ≈ 90%, yet differentiating the depth of invasion remains impossible with transaxial imaging [6]. Retrograde pyelography also aids the diagnosis, but reported sensitivities as low as 25% remain a limitation when trying to diagnose tumour recurrence [1]. Cytology also has diagnostic limitations, especially for patients with low-grade and -stage lesions [13]. For patients treated with endoscopic techniques, only a 20–28% positive cytology rate has been reported [4,5].

When clinical suspicion is high or abnormalities are encountered, ureteroscopy is the most important intervention. Using modern semirigid and flexible ureteroscopes, the entire collecting system can be inspected. Ideally, the visualized lesion is then biopsied using a flat-wire basket or 3 F forceps. Frozen-section analysis of the specimen is preferred, thereby facilitating definitive treatment during the same anaesthetic. Specimens can also be processed using cytological techniques to improve the diagnostic yield [14]. However, in some instances the visible appearance of the lesion alone is sufficient to guide therapy [4,5].

TECHNICAL CONSIDERATIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

Ureteroscopic and percutaneous techniques have been previously described in detail [1–7]. Ureteroscopy appears advantageous as a closed urinary system is maintained and the approach is the least invasive. Similar to urinary stone treatment, ureteric lesions are easier to treat than more proximal lesions in the calyces or renal pelvis. However, treatment is limited by ureteric wall thickness, as any perforation may spread tumour cells. Fulguration is applied with electrocautery, the Nd:YAG laser, or more commonly nowadays with the Ho:YAG laser. For patients with absolute indications for endoscopy, incomplete ureteroscopic resection justifies an attempt with percutaneous resection. Other patients undergo nephroureterectomy for incomplete resection or when criteria for conservative treatment are not fulfilled [4–7].

For bulky renal pelvic or calyceal tumours, percutaneous resection is often advantageous; it is especially desirable for patients with a solitary kidney who have bulky disease, as visualization and resection are improved. Percutaneous management is also indicated in some patients after cystectomy. Renal access is obtained similarly to that used for percutaneous nephrolithotomy. The tumour is resected with a standard resectoscope and an Amplatz sheath to minimize the risk of tumour seeding.

INTRACAVITARY THERAPY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

Adjuvant BCG, mitomycin C or thiotepa intracavitary therapy can be administered via an antegrade nephrostomy or retrograde via a JJ stent. Specific treatment details have been described [4,5,7,15,16]. Some groups have recently suggested that retrograde administration is inferior to antegrade treatment, as the delivery depends on reflux into the upper tract [17]. Intracavitary therapy is typically initiated 2–4 weeks after resection when there is no gross haematuria or urinary infection. When delivered via an antegrade nephrostomy a nephrostogram is taken to confirm the tube position before treatment. Especially during antegrade BCG administration, low-pressure delivery is paramount [6].

SURVEILLANCE PROTOCOLS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

Surveillance after endourological treatment includes excretory urography, cystoscopy, urine cytology and often retrograde pyelography. In addition, the threshold for a ureteroscopic evaluation should be low; indeed, some recommend periodic ureteroscopy as part of routine surveillance [1,13]. Keeley et al.[1] recommended lifelong ureteroscopic surveillance, as they found that imaging can miss 75% of tumours detected ureteroscopically. Among 23 patients on surveillance, Chen et al.[13] also reported the sensitivity of ureteroscopy (93%) was higher than that of intraoperative pyelography (72%) or bladder cytology (50%). However, as patients treated endoscopically already have a very favourable prognosis and are closely monitored, the significance of undetectable recurrences on imaging may be questioned. Ongoing clinical experience will determine the best surveillance protocol from the standpoint of outcome and cost-effectiveness.

COMPLICATIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

The complications of endourological treatment are similar to those with urinary stone treatment. Likewise, the incidence and severity of complications has decreased with advances in endourology. Ureteric perforations and strictures are the most common complications associated with ureteroscopic treatment of TCC [1,4,5]. Ureteric strictures may also occur after endourological treatment in 5–13% of cases [1,4,5,12]. The Ho:YAG laser may minimize the risk of stricture, e.g. Keeley et al.[1] reported no strictures with the Ho:YAG laser, compared with two associated with the Nd:YAG laser. Access complications and bleeding are the most common complications associated with the percutaneous treatment of upper tract TCC [2,6,7].

Tumour seeding is a unique complication of endourological treatment for TCC. Even with ureteroscopy, malignant cells may migrate via ureteric perforations or secondary to high intracavitary pressures generated by irrigation fluid. Among 18 patients undergoing intraoperative pyeloscopy followed by immediate nephroureterectomy, Tomera et al.[18] reported a retroperitoneal recurrence in two at the 3-year follow-up. Furthermore, Lim et al.[19] noted pyelolymphatic and pyelovenous cell migration after ureteroscopic treatment for TCC. Nonetheless, Hendin et al.[20] found that long-term progression and cause-specific survival were not influenced by diagnostic ureteroscopy in patients with upper tract TCC. Tumour seeding is also a concern after percutaneous resection, but the risk of tract recurrence for appropriately selected patients appears to be minimal [2,7]. Tract recurrence has only been reported in patients with advanced disease who are not optimal candidates for conservative therapy, or for patients who developed tract seeding not in the context of upper tract TCC resection [21,22]. For instance, Jarrett et al.[2] noted tract recurrence in one patient with advanced disease discovered incidentally during percutaneous nephrolithotomy.

Intracavitary therapy also causes unique complications when used in managing upper tract TCC. For the most part, major complications related to intracavitary therapy have been avoided with careful treatment precautions. In addition, intracavitary therapy has caused no adverse effects on renal function [17]. Complications have included minor temperature increases, minor BCG-related symptoms, and fungal infections [2,3,7,17]. To date, severe complications related to intracavitary therapy are exceedingly rare [2,17]. Among 37 patients undergoing BCG therapy, Thalmann et al.[17] recently reported one who had BCG inflammation and two who developed severe septicaemia after the first infusion of BCG. In addition, Jarrett et al.[2] reported one death after BCG administration, but the cause was not absolutely known, as there was no postmortem examination.

OUTCOME

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

Pathological grade and stage have typically dictated the prognosis for upper tract TCC. Furthermore, grade often directly correlates with stage [10,11,23], e.g. Murphy et al.[11] reported that 47 of 49 patients with grade 1 tumours also had stage I disease. Disease recurrence and survival are also influenced by grade; Zincke and Neves [10] noted a 5% recurrence rate for grade 1 and 2 tumours, compared with 50% for grade 3 tumours managed with conservative open surgery. Grade and stage also appear to be more important determinants of survival than a specific surgical intervention. Among 49 patients with grade 1 TCC, compared with age-matched controls, survival was independent of treatment type [11]. However, Murphy et al.[23] reported that disease was difficult to control even with radical surgery among 79 patients with grade 3 and 4 tumours.

Endourological treatments have yielded similar results; among 30 biopsies with low or moderate grade obtained ureteroscopically, Keeley et al.[14] found that 27 patients ultimately had low or moderate grade in the surgical specimen, and 26 ultimately had stage I tumours. On the other hand, eight of 12 patients with high-grade biopsies had tumour invasion in the final specimen [14]. In addition, disease recurrence, development of metastasis and cause-specific survival appear to be largely influenced by histological grade rather than the choice of conservative endoscopic therapy. Jarrett et al.[2] reported recurrence rates of 18%, 33% and 50% for grade 1, 2 and 3 tumours, respectively; they also reported that grade was predictive of cancer-related deaths and indeed cancer-related deaths were only among patients with grade 3 tumours [2]. As such, endourological treatment was subsequently recommended only for grade 1 and 2 tumours, while nephroureterectomy was favoured for grade 3 tumours. In updated survival data from Long Island Jewish Hospital at a mean follow-up of 49 months, survival rates for the percutaneous treatment of grade 1, 2 and 3 tumours were 100%, 96% and 64%, respectively [6]. Likewise, Patel et al.[24] used percutaneous treatment for 28 patients and reported an estimated local recurrence-free survival of 86%, cause-specific survival of 91% and overall survival of 78% at the 3-year follow-up. Furthermore, Lee et al.[25] compared nephroureterectomy and percutaneous surgery in patients with upper tract TCC; for patients with grade 1 and 2 tumours the disease-free survival was similar regardless of treatment approach. Conversely, grade 3 tumours had a poor prognosis and a higher risk of metastasis, regardless of the type of treatment selected [25].

Conservative endoscopic treatment with ureteroscopy has also yielded similar results. At a mean follow-up of 5 years, Elliott et al.[4] reported survival rates for grade 1, 2 and 3 tumours of 100%, 80% and 60%, respectively. Among the 44 treated patients, 17 (39%) had a local recurrence. For ureteric and renal pelvic tumours, the mean times to developing tumour recurrence were 18 and 7 months, respectively [4]. Similarly, Keeley et al.[1] treated 38 patients ureteroscopically for upper tract TCC; at the most recent follow-up of 35 months, 86% of patients were tumour-free. A recurrence rate of 29% (eight patients) was reported, but all were subsequently treated ureteroscopically and none had disease progression [1]. Patel and Fuchs [16] treated 17 renal units in 13 patients ureteroscopically, reporting only two recurrences and 15 kidneys preserved at a mean follow-up of 15 months. Another report by Grasso et al.[26] also confirmed the effectiveness of ureteroscopy for treating low-grade upper tract TCC. Among the 20 patients in the series, 11 with low-grade lesions had complete disease-specific survival, with renal preservation in nine. However, the remaining nine patients with higher grade lesions more often required nephroureterectomy secondary to disease recurrence and progression [26].

Conservative endoscopic therapy also appears to be safe and effective for selected patients with normal contralateral kidneys. Elliott et al.[5], over an 11-year period, treated 21 patients ureteroscopically, all having upper tract TCC and a normal contralateral kidney. All tumours were low-grade and -stage, with a tumour diameter of < 2.0 cm. Overall, the recurrence rate was 38% and no patient with a recurrent tumour had an increase in grade. In addition, no patient died as a result of the conservative management of upper tract TCC, and the renal preservation rate was 81%. Likewise, Chen and Bagley [9] reviewed the ureteroscopic management of upper tract TCC in patients with normal contralateral kidneys. Among 23 patients, 35% remained tumour-free at a mean follow-up of 35 months, while the remaining 15 (65%) were treated for recurrence. At the last follow-up the disease-specific survival was 100% and the renal preservation rate 83%[9]. Success rates for elective percutaneous resection of upper tract tumours have also yielded similar results [2,6].

Other prognostic factors have been identified with endourological TCC treatment. For example, an absolute indication for endourological treatment portends a worse prognosis. Keeley et al.[1] found that patients with elective or relative indications had a tumour-free rate of 89%, while the tumour-free rate for 22 patients with absolute/palliative indications was 50%. In addition to grade, investigators have also found tumour size and multifocality to be significantly associated with tumour persistence and recurrence [1,24]. A history of bladder cancer is also predictive of upper tract recurrence after endoscopic treatment [7,12], although Elliott et al.[4] reported a trend to significance for grade, but not for a previous history of TCC, age or gender. Importantly, endourological treatment performed ureteroscopically or via a percutaneous approach does not appear to increase the risk of metachronous bladder lesions. The bladder cancer incidence was 25–33% after nephroureterectomy, compared with 18–37% after conservative endourological treatment [1,7,12].

The results of adjuvant intracavitary therapy for upper tract TCC are mixed. Indeed, adjuvant therapy is often selected for patients at increased risk of recurrence. Intracavitary therapy has been used after treating papillary tumours and carcinoma in situ (CIS). Mitomycin C and BCG have been used more frequently and possibly with more encouraging results. For instance, Martinez-Pineiro et al.[12] used thiotepa, mitomycin C, BCG, or interferon-α after endoscopic resection and reported lower recurrence rates with BCG (12.5%) and mitomycin C (14.2%). Keeley et al.[15] used mitomycin C in 38 patients, of whom 15 were thought to be at high risk of recurrence. While there were no significant side-effects the ipsilateral recurrence rate was 54%. Better results may be possible for lower grade lesions. For instance, Patel and Fuchs [16] treated 13 patients with lower grade disease after ureteroscopic ablation and reported an 88% tumour-free rate at a mean follow-up of 15 months. Likewise, Liatsikos et al.[6] found that BCG was most helpful for patients with grade 1 disease; among 15 such patients, seven received BCG and one had disease recurrence. Among eight patients with grade 1 disease and not receiving BCG, four had a recurrence. The recurrence rate for grade 2 and 3 tumours was unaffected by adjuvant BCG [6]. However, Martinez-Pineiro et al.[12] reported limited effectiveness of BCG for grade 2 and 3 tumours; there was a 23% recurrence rate for patients receiving BCG, compared with 50% for those not receiving BCG. Conversely, Thalmann et al.[17] reported that papillary tumour recurrences in the upper tract could not be prevented with BCG; at a median follow-up of 10 months, 87% of patients treated had recurrent or progressive disease.

The use of BCG for CIS has also yielded conflicting results in the upper tract. At a 36-month follow-up, Sharpe et al.[27] reported normal cytology in eight of 11 patients with CIS after retrograde BCG administration, and Studer et al.[28] reported seven of eight patients with normal cytology after BCG therapy at a follow-up of 18–24 months. In comparison, Patel and Fuchs [16] found that treating CIS resulted in only 32% of renal units remaining disease-free at 51 months of follow-up. Thalman et al.[17] also noted that > 30% of patients had persistently abnormal cytology after treatment with BCG for CIS, with a longer follow-up (median 42 months); indeed, from these results, Thalmann et al. postulated that BCG may lose therapeutic effectiveness for treating CIS over time.

The role of adjuvant therapy in managing upper tract TCC remains poorly understood. The beneficial effect is difficult to assess given the variety of intracavitary agents, varying routes of administration and treatment protocols, and lack of prospective randomized trials. Questions remain, such as the optimal route of administration, duration of therapy and intracavitary agent. Other concerns are the cost-effectiveness of therapy and the risk of treatment complications. A longer follow-up and prospective randomized studies are warranted to determine the benefits of intracavitary therapy, especially for the optimal agent, route of administration, treatment duration, cost-effectiveness and morbidity.

CONCLUSIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES

For selected patients with upper tract TCC, endourological techniques can provide effective, minimally invasive therapy and can maintain the quality of life by avoiding the need for dialysis. With advances in ureteroscopy and percutaneous techniques, the ease, safety and applicability of endourological approaches has increased. Endourological resection is warranted for patients with a solitary kidney, bilateral synchronous disease, renal insufficiency or significant comorbidity precluding nephroureterectomy. While imperative indications remain the best reason for using endourological techniques, elective indications have been increasingly applied for selected patients with normal contralateral kidneys (i.e. small, solitary, low-grade tumours). While conservative therapy appears favourable for selected patients with normal contralateral kidneys, additional long-term outcome data are required to consolidate treatment recommendations. In addition, the role of adjuvant therapy after endourological resection requires further investigation, ideally using randomized control trials.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. RATIONALE
  5. PREOPERATIVE EVALUATION
  6. TECHNICAL CONSIDERATIONS
  7. INTRACAVITARY THERAPY
  8. SURVEILLANCE PROTOCOLS
  9. COMPLICATIONS
  10. OUTCOME
  11. CONCLUSIONS
  12. REFERENCES