Ureteroscopic and percutaneous management of upper tract urothelial carcinoma (UTUC): systematic review

What's known on the subject? and What does the study add? Endoscopic management of upper tract urothelial carcinoma (UTUC) using either ureteroscopy and laser ablation, or percutaneous resection, is a management option for treating selected low‐grade tumours with favourable characteristics. However, the evidence base for such practice is relatively weak, as the reported experience is mainly limited to small case series (level of evidence 4), or non‐randomised comparative studies that are unmatched for tumour stage (level of evidence 3b), with variability of follow‐up duration and reported outcome measures. The present systematic review comprehensively reviews the outcomes of all studies of endoscopic management of UTUC, including the role of topical adjuvant therapy. It establishes for the first time a structured reference for endoscopic management of UTUC, and is a foundation for further clinical studies.

OBJECTIVE

• ? To systematically review the oncological outcomes of upper tract urothelial carcinoma (UTUC) treated with ureteroscopic and percutaneous management.
• ? The standard treatment of UTUC is radical nephroureterectomy (RNU). However, over the last two decades several institutions have treated UTUC endoscopically, either via ureteroscopic ablation or percutaneous nephroscopic resection of tumour (PNRT), for both imperative and elective indications.

METHODS

• ? For evidence acquisition the Pubmed database was searched for English language publications in December 2011 using the following terms: upper tract (UT) transitional cell carcinoma (TCC), upper tract TCC, UTTCC, upper tract urothelial cell carcinoma, upper tract urothelial carcinoma, UTUC, endoscopic management, ureteroscopic management, laser ablation, percutaneous management, PNRT, conservative management, ureteroscopic biopsy, biopsy, BCG, mitomycin C, topical therapy.

RESULTS

• ? There are no randomised trials comparing endoscopic management with RNU. Most published studies were retrospective case series (and database reviews), or unmatched comparative studies.
• ? There was strong selection bias for favourable tumour characteristics in many endoscopically treated groups.
• ? There was variation in medical comorbidity and indication for treatment across different study groups.
• ? The biopsy verification of underlying UTUC pathology was inconsistent.
• ? The follow‐up in most studies was limited, typically to a mean 3 years.

CONCLUSIONS

• ? There is a high rate of UT recurrence with endoscopically managed UTUC, and a grade‐related risk of tumour progression and disease‐specific mortality.
• ? Overall, renal preservation may be high with ≈20% of patients proceeding eventually to RNU. For highly selected Grade 1 (or low‐grade) disease managed in experienced centres, 5‐year disease‐specific survival (DSS) may be equivalent to RNU, although the small study groups and short follow‐ups preclude comments on less favourable Grade 1 (or low‐grade) tumour characteristics, or DSS, in the longer‐term.
• ? For Grade 3 (or high‐grade) disease, DSS outcomes are poor and endoscopic management should only be considered for compelling imperative indications in the context of the patient's overall life expectancy and competing comorbidity.

     

Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In an array of urological and non‐urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20‐year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI‐positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI‐positive disease have overall survival outcomes similar to those of patients with muscle‐invasive LVI‐negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC.

OBJECTIVE

• ? To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

PATIENTS AND METHODS

• ? The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified.
• ? These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log‐rank tests and Cox proportional hazards regression models.
• ? Actuarial survival curves were calculated using the Kaplan–Meier method.

RESULTS

• ? LVI was observed in 68 patients (32.2%).
• ? The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5‐ and 10‐year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively.
• ? In multivariate analysis, age, race and LVI were independent predictors of overall survival.

CONCLUSIONS

• ? The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC.
• ? LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options.
• ? With confirmation from large international studies, inclusion of LVI in the tumour‐node‐metastasis staging system for UTUC should be considered.

     

Perivesical fat invasion in bladder cancer: implications for prognosis comparing pT2b,pT3a and pT3b stages and consequences for adjuvant chemotherapy indications

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The more that bladder cancer progresses from the urothelium to the outside of the bladder the worse the prognosis. To date, the use of adjuvant chemotherapy has not been completely defined. The present study clarifies the prognosis and benefits of adjuvant chemotherapy for different stages of bladder cancer that invade perivesical fat.

OBJECTIVE

• ? To assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical cystectomy (RC) in order to define potential situations where chemotherapy may be of benefit.

PATIENTS AND METHODS

• ? Between 1985 and 2009, 903 patients underwent a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre.
• ? In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour, and 129 patients (14.3%) a pT3b tumour.
• ? The median (range) overall follow‐up was 23 (1–350) months.
• ? Overall (OS), disease‐specific (DSS), metastases‐free (MFS) and local recurrence‐free survival (LRFS) was estimated and compared using Kaplan–Meier plots and log‐rank test.

RESULTS

• ? The 5‐year survivals pT2b and pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%, 44%, 40%, and 31% respectively).
• ? In pN0 disease, MFS differences between pT2b–pT3a and pT3b tumours were not significant in patients who had received adjuvant chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%, respectively).

CONCLUSIONS

• ? Bladder cancers invading perivesical tissue macroscopically have a greater propensity to produce lymph node metastases, local recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may receive more benefit from adjuvant chemotherapy.
• ? Our results could be a useful for selecting patients for adjuvant chemotherapy.

     

Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? In patients treated with radical cystectomy, pelvic lymph node dissection may have a beneficial effect on cancer control outcomes. We examined the effect of pelvic lymph node dissection on stage‐specific cancer control outcomes.

OBJECTIVE

• ? To examine the effect of stage‐specific pelvic lymph node dissection (PLND) on cancer‐specific (CSM) and overall mortality (OM) rates at radical cystectomy (RC) for bladder cancer.

METHODS

• ? Overall, 11 183 patients were treated with RC within the Surveillance, Epidemiology, and End Results database.
• ? Univariable and multivariable Cox regression analyses tested the effect of PLND on CSM and OM rates, after stratifying according to pathological tumour stage.

RESULTS

• ? Overall, PLND was omitted in 25% of patients, and in 50, 35, 27, 16 and 23% of patients with respectively pTa/is, pT1, pT2, pT3 and pT4 disease (P < 0.001).
• ? For the same stages, the 10‐year CSM‐free rates for patients undergoing PLND compared with those with no PLND were, respectively, 80 vs 71.9% (P = 0.02), 81.7 vs 70.0% (P < 0.001), 71.5 vs 56.1% (P = 0.001), 43.7 vs 38.8% (P = 0.006), and 35.1 vs 32.0% (P = 0.1).
• ? In multivariable analyses, PLND omission was associated with a higher CSM in patients with pTa/is, pT1 and pT2 disease (all P ≤ 0.01), but failed to achieve independent predictor status in patients with pT3 and pT4 disease (both P ≥ 0.05).
• ? Omitting PLND predisposed to a higher OM across all tumour stages (all P ≤ 0.03).

CONCLUSIONS

• ? Our results indicate that PLND was more frequently omitted in patients with organ‐confined disease.
• ? The beneficial effect of PLND on cancer control outcomes was more evident in these patients than in those with pT3 or pT4 disease.
• ? PLND at RC should always be considered, regardless of tumour stage.

     

Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single-centre study

Study Type – Therapy (individual cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Tumour enucleation was demonstrated to be an oncologically safe conservative treatment for small renal masses in agreement with the EAU guidelines. Nevertheless, the theoretical increased risk of positive surgical margins and local recurrence, led some authors to hypothesize a possible key role of laser or diathermy ablation of the tumour bed to free the kidney parenchyma from any tumour cells that extended in the kidney parenchyma. Our pathological and clinical results showed that tumour enucleation with no ablation of the tumour bed (e.g. diathermy, argon beam or Nd‐YAG laser) can ensure negative surgical margins and it is not associated with an increased risk of local recurrence.

OBJECTIVE

• ? To prospectively evaluate the risk of positive surgical margins and local recurrence after blunt tumour enucleation (TE) with no ablation of the tumour bed.

PATIENTS AND METHODS

• ? Between 2005 and 2007, data were gathered prospectively from 201 consecutive patients who had open TE with no ablation of the tumour bed.
• ? Overall, 164 consecutive patients had TE for single sporadic renal cell carcinoma (RCC).
• ? All patients had an abdominal computed tomography (CT) at the last follow‐up visit.

RESULTS

• ? The pathological review showed that 70.2% of tumours were pT1a, 18.9% were pT1b, 1.8% were pT2 and 9.1% were pT3a.
• ? The mean (range, interquartile range) tumour greatest dimension was 3.5 (0.5–12.5, 2.4–4.1) cm.
• ? Although no deliberate attempt to resect normal parenchyma was performed, the pathological analysis showed the presence of a thin layer of parenchyma with a mean (range) thickness of 0.97 (0.31–1.60) mm, around the tumour. None of the patients had positive surgical margins.
• ? At a mean (median, range) follow up of 40 (38, 25–62) months, three (1.8%) patients had local recurrence, of whom one (0.6%) had a true local recurrence at the enucleation site detected 35 months after surgery, while two had kidney recurrence elsewhere associated with concurrent systemic metastases diagnosed 16 and 13 months after surgery.

CONCLUSIONS

• ? TE with no ablation of the tumour bed is a safe technique with a local recurrence rate of 0.6%.
• ? The histopathological analysis showed the presence of a minimal tumour‐free surgical margin, although no deliberate attempt to resect normal parenchyma is performed.

     

Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study

Study Type – Therapy (multi‐centre retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT‐UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the ‘gold‐standard’ treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT‐UCs. Due to the paucity of cases of UUT‐UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi‐institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5‐year probability of cancer‐specific survival, recurrence‐free survival and metastasis‐free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases.

OBJECTIVE

• ? To compare recurrence‐free survival (RFS), metastasis‐free survival (MFS) and cancer‐specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT‐UC) located in the ureter.

PATIENTS AND METHODS

• ? We performed a multi‐institutional retrospective review of patients with UUT‐UC who had undergone RNU or SU between 1995 and 2010.
• ? Type of surgery, Tumour‐Node‐Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival.

RESULTS

• ? In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow‐up was 26 (10–48) months.
• ? The 5‐year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P= 0.99); 37% and 47.9%, respectively (P= 0.48); 81.9% and 85.4%, respectively (P= 0.51).
• ? In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P= 0.94, 0.42 and 0.53, respectively).
• ? In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P= 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P= 0.001, 0.04, 0.009 and 0.001, respectively).
• ? The main limitation of the study is its retrospective design, which is due to the rarity of the disease.

CONCLUSIONS

• ? Short‐term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT‐UC in select cases and should be considered an option.
• ? In every other case, RNU still represents the ‘gold standard’ for the treatment of UUT‐UC.

     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

Significant impact of age at diagnosis on the prognosis of Japanese patients with pT1 renal cell carcinoma following surgical resection

Study Type – Prognosis (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Several parameters significantly associated with the prognosis of patients with small venal cell carcinoma (RCC) have been reported; however, the outcomes described in such studies are not totally consistent, and the majority of these studies were based on the data from Western populations. Age of diagnosis is a significant predictor of disease recurrence as well as overall survivals in Japanese patients with pT1 RCC following surgical resection; therefore, intensive follow‐up of older patients is necessary even for those with pT1 RCC.

OBJECTIVE

• ? To retrospectively review oncological outcomes following surgical resection in Japanese patients with pT1 renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? The present study included a total of 832 consecutive Japanese patients who underwent either radical or partial nephrectomy and were subsequently diagnosed as having localized pT1 RCC.
• ? The significance of several clinicopathological factors in their postoperative outcomes was analysed.

RESULTS

• ? The median (range) age of the 832 patients was 66 (31–90) years. Radical and partial nephrectomies were performed for 710 patients (85.3%) and 122 patients (14.7%), respectively. Distribution of pathological stage was pT1a in 582 patients (70.0%) and pT1b in 250 patients (30.0%).
• ? During the observation period (median 44 months, range 3–114 months), postoperative disease recurrence developed in 38 patients (4.6%) and death occurred in 34 (4.1%). The 5‐year recurrence‐free and overall survival rates were 93.6% and 94.1%, respectively.
• ? Of several factors examined, only age at diagnosis was identified as an independent predictor of both postoperative disease recurrence and overall survival in these patients. Furthermore, there were significant differences in the recurrence‐free and overall survivals among patient groups stratified by age at diagnosis.

CONCLUSION

• ? These findings suggest that age at diagnosis is a significant predictor of disease recurrence as well as overall survival in patients with pT1 RCC following surgical resection; therefore, intensive follow‐up of older patients is necessary even for those with pT1 RCC.

     

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population‐based study

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Given the natural history of pT4 urothelial carcinoma of the urinary bladder, and the substantially poorer survival of pT4 patients relative to pT3, it may be argued that radical cystectomy is not justified in these patients. Relying on a large population‐based retrospective analysis, the current study identified two main categories of patients with pT4 urothelial carcinoma of the urinary bladder. The first comprised of patients with pT4b disease, whose disease phenotype was clearly more aggressive than their pT3 counterparts. The second group consisted of patients with pT4a disease, whose disease phenotype was very similar to patients with pT3. These findings indicate that patients with pT4b disease should be provided with the maximal amount of therapeutic interventions, such as administration of early adjuvant chemotherapy and perhaps early adjuvant radiotherapy.

OBJECTIVE

• ? To examine cancer‐specific mortality (CSM) in patients with pT4N_0–3M₀ urothelial carcinoma of the urinary bladder (UCUB) and to compare it to patients with pT3N_0–3M₀, in a population‐based cohort treated with radical cystectomy (RC).

PATIENTS AND METHODS

• ? RCs were performed in 5625 pT3‐T4bN_0–3M₀ patients with UCUB within 17 Surveillance, Epidemiology and End Results (SEER) registries between 1988 and 2006.
• ? Univariable and multivariable models tested the effect of pT4a vs pT4b vs pT3 stages on CSM.
• ? Covariates consisted of age, gender, race, lymph node status and SEER registries.
• ? All analyses were repeated in 3635 pN₀ patients.

RESULTS

• ? Of 5625 patients, 2043 (36.3%) had pT4aN_0–3, 248 (4.4%) had pT4bN_0–3 and 3334 had pT3N_0–3 (59.3%) UCUB.
• ? The 5‐year CSM was 57.6% vs 81.7% vs 53.9% for, respectively, pT4aN_0–3 vs pT4bN_0–3 vs pT3N_0–3 patients (all log‐rank P= 0.008).
• ? In multivariable analyses the rate of CSM was 2.3‐fold higher in pT4b vs pT3 (P < 0.001), 1.1‐fold higher in pT4a vs pT3 (P= 0.002) and 2.0‐fold higher in pT4a vs pT4b patients.
• ? After restriction to pN₀ stage, pT4b patients had a 2.3‐fold higher rate of CSM than pT3 patients (P < 0.001) and pT4b patients had a 2.1‐fold higher rate of CSM than pT4a patients (P < 0.001).
• ? The CSM rate was the same for pT4a and pT3 patients (P= 0.1).

CONCLUSIONS

• ? Our findings indicate that patients with pT4a UCUB have similar CSM as those with pT3 UCUB.
• ? Consequently, RC should be given equal consideration in patients with pT3 and pT4a UCUB.

     

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi-institutional study

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Few studies supported the expanded indications for nephron‐sparing surgery (NSS) in selected patients with 4.1 cm renal tumours in the size range (T1b). However, all these comparative studies included both imperative and elective partial nephrectomy and patient selection for analysis was based on pathological stage (pT1) and not on clinical stage (cT1). Patients with clinically organ‐confined RCC (cT1) who are candidates for elective PN have a limited risk of clinical understaging. NSS is not associated with an increased risk of recurrence and cancer‐specific mortality both in cT1a and cT1b tumours

OBJECTIVE

• ? To compare the oncological outcomes of patients who underwent elective partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organ‐confined renal masses ≤7 cm in size (cT1).

PATIENTS AND METHODS

• ? The records of 3480 patients with cT1N0M0 disease were extracted from a multi‐institutional database and analyzed retrospectively.

RESULTS

• ? In patients who underwent PN, the risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases.
• ? With regard to the cT1a patients, the 5‐ and 10‐year cancer‐specific survival (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%, respectively, after PN (log‐rank test: P = 0.01).
• ? With regard to cT1b patients, the 5‐year CSS probabilities were 92.6% after RN and 90% after PN, respectively (log‐rank test: P = 0.89).
• ? Surgical treatment failed to be an independent predictor of CSS on multivariable analysis, both for cT1a and cT1b patients.
• ? Interestingly, PN was oncologically equivalent to RN also in patients with pT3a tumours (log‐rank test: P = 0.91).

CONCLUSIONS

• ? Elective PN is not associated with an increased risk of recurrence and cancer‐specific mortality in both cT1a and cT1b tumours.
• ? Data from the present study strongly support the use of partial nephrectomy in patients with clinically T1 tumours, according to the current recommendations of the international guidelines.

     

Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non‐muscle‐invasive bladder cancer. Owing to high recurrence and progression rates, a two‐pronged strict surveillance regimen, consisting of both functional and oncological follow‐up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node‐positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi‐institutional project lends further support to the continued use of risk‐stratified follow‐up and emphasizes the need for earlier strict surveillance in patients with extravesical and node‐positive disease.

OBJECTIVES

• ? To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC).
• ? To establish appropriate surveillance protocols.

PATIENTS AND METHODS

• ? We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres.
• ? Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study.

RESULTS

• ? A total of 825 patients (43.6%) developed recurrence.
• ? According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant.
• ? The median (range) time to recurrence for the entire population was 10.1 (1–192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively.
• ? According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5‐yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1–72 months) than ≥pT3N0 tumours (10 months, range 1–70 months) or ≤pT2N0 tumours (14 months, range 1–192 months, P < 0.001).

CONCLUSIONS

• ? Differences in recurrence patterns after RC suggest the need for varied follow‐up protocols for each group.
• ? We propose a stage‐based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over‐investigation.

     

Long‐term endoscopic management of upper tract urothelial carcinoma: 20‐year single‐centre experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Endoscopic management of small, low‐grade, non‐invasive upper tract urothelial cell carcinoma (UTUC) is a management option for selected groups of patients. However, the long‐term survival outcomes of endoscopically‐managed UTUC are uncertain because only four institutions have reported outcomes of more than 40 patients beyond 50 months of follow‐up. Moreover, there is significant variance in the degree of underlying UTUC pathology verification in some of these reports, which precludes an analysis of disease‐specific survival outcomes. The present study represents one of the largest endoscopically managed series of patients with UTUC, with a long‐term follow‐up. The degree of verification of underlying UTUC pathology is one of the highest, which allows a grade‐stratified analysis of different outcomes, including upper‐tract recurrence‐free survival, intravesical recurrence‐free survival, renal unit survival and disease‐specific survival. These outcomes provide further evidence suggesting that endoscopic management of highly selected, low‐grade UTUC can provide effective oncological control, as well as renal preservation, in experienced centres.

OBJECTIVE

• ? To report the long‐term outcomes of patients with upper tract urothelial cell carcinoma (UTUC) who were treated endoscopically (either via ureteroscopic ablation or percutaneous resection) at a single institution over a 20‐year period.

PATIENTS AND METHODS

• ? Departmental operation records were reviewed to identify patients who underwent endoscopic management of UTUC as their primary treatment.
• ? Outcomes were obtained via retrospective analysis of notes, electronic records and registry data.
• ? Survival outcomes, including overall survival (OS), UTUC‐specific survival (disease‐specific survival; DSS), upper‐tract recurrence‐free survival, intravesical recurrence‐free survival, renal unit survival and progression‐free survival, were estimated using Kaplan–Meier methods and grade‐stratified differences were analyzed using the log‐rank test.

RESULTS

• ? Between January 1991 and April 2011, 73 patients underwent endoscopic management of UTUC with a median age at diagnosis of 67.7 years.
• ? All patients underwent ureteroscopy and biopsy‐confirmation of pathology was obtained in 81% (n= 59) of the patients. In total, 14% (n= 10) of the patients underwent percutaneous resection.
• ? Median (range; mean) follow‐up was 54 (1–223; 62.8) months.
• ? Upper tract recurrence occurred in 68% (n= 50). Eventually, 19% (n= 14) of the patients proceeded to nephroureterectomy.
• ? The estimated OS and DSS were 69.7% and 88.9%, respectively, at 5 years, and 40.3% and 77.4%, respectively, at 10 years. The estimated mean and median OS times were 119 months and 107 months, respectively. The estimated mean DSS time was 190 months.

CONCLUSIONS

• ? The present study represents one of the largest reported series of endoscopically‐managed UTUC, with high pathological verification and long‐term follow‐up.
• ? Upper‐tract recurrence is common, which mandates regular ureteroscopic surveillance.
• ? However, in selected patients, this approach has a favourable DSS, with a relatively low nephroureterectomy rate, and therefore provides oncological control and renal preservation in patients more likely to die eventually from other causes.

     

Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pT1 clear-cell renal cell carcinoma

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three‐dimensional tumour volume (cm³) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC‐specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC.

OBJECTIVE

• ? To address whether information on three‐dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone.

PATIENTS AND METHODS

• ? We identified 955 patients treated with radical nephrectomy or nephron‐sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non‐cystic clear‐cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients.
• ? We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis.
• ? Univariate and multivariable associations with RCC‐specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS

• ? Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30–15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83–7.85; P= 0.10).
• ? Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients.
• ? Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC‐specific death were similar.
• ? Multivariable adjustment did not alter our findings.

CONCLUSIONS

• ? Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC.
• ? Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.

     

Subclassification of pT3 urothelial carcinoma of the renal pelvicalyceal system is associated with recurrence-free and cancer-specific survival: proposal for a revision of the current TNM classification

Background

The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable.

Objectives

The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients.

Design, setting, and participants

From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

Intervention

RNU.

Measurements

Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses.

Results and limitations

Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p < 0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p = 0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p = 0.003) and cancer-specific mortality (HR: 1.7; p = 0.02). The major limitation is the retrospective character of the study.

Conclusions

Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer–International Union Against Cancer TNM classification system.     

Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carcinoma (RCC) in the USA: a propensity scoring approach

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Partial nephrectomy has become the standard of care for T1a renal tumours, and the application of nephron‐sparing techniques has increasingly been expanded to patients with localized T1b cancers. However, the relative efficacy of partial versus radical nephrectomy for these medium‐sized tumours has yet to be definitively established. This study employs a propensity scoring approach within a large US population‐based cohort to determine that no survival differences exist among patients with T1b renal tumours undergoing partial versus radical nephrectomy.

OBJECTIVES

• ? To compare survival after partial nephrectomy (PN) vs radical nephrectomy (RN) among patients with stage TIb renal cell carcinoma (RCC) using a propensity scoring approach.
• ? Propensity score analysis is a statistical methodology that controls for non‐random assignment of patients in observational studies.

PATIENTS AND METHODS

• ? Using the Surveillance, Epidemiology, and End Results registry, 11 256 cases of RCCs of 4–7 cm that underwent PN or RN between 1998 and 2007 were identified.
• ? Propensity score analysis was used to adjust for potential differences in baseline characteristics between patients in the two treatment groups.
• ? Overall survival (OS) and cancer‐specific survival (CSS) of patients undergoing PN vs RN was compared in stratified and adjusted analysis, controlling for propensity scores.

RESULTS

• ? In all, 1047 (9.3%) patients underwent PN. For the entire cohort, no difference in survival was found in patients treated with PN as compared with RN, as shown by the adjusted hazard ratio (HR) for OS (1.10; 95% confidence interval [CI]: 0.91–1.36) and renal‐CSS (HR 0.91; 95% CI: 0.65–1.27).
• ? When the cohort was stratified by tumour size and age, no difference in survival was identified between the groups.

CONCLUSIONS

• ? Even when stratified by tumour size and age, a survival difference between PN and RN in a propensity‐adjusted cohort of patients with T1b RCC could not be confirmed.
• ? If validated in prospective studies, PN may become the preferred treatment for T1b renal tumours in centres experienced with nephron‐sparing surgery.

     

'Zero ischaemia', sutureless laparoscopic partial nephrectomy for renal tumours with a low nephrometry score

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Ischaemic injury produced by hilar clamping during partial nephrectomy is the main determinant of renal function loss. The exact measurement of ipsilateral renal function loss can be underestimated by serum creatinine levels and estimated GFR. Few reports of unclamped laparoscopic partial nephrectomy (LPN) are available in the literature, although this technique shows promising results. The present study includes a series of patients with the longest follow‐up of LPN without hilar clamping and without parenchymal reconstruction. Excellent cancer control and optimum renal functional preservation suggest that this technique could be performed in selected patients, i.e. those with small and peripheral tumours (also classified as low nephrometry score tumours).

OBJECTIVE

• ? To describe the technique and report the results of ‘zero ischaemia’, sutureless laparoscopic partial nephrectomy (LPN) for renal tumours with a low nephrometry score.

PATIENTS AND METHODS

• ? Between August 2003 and January 2010, data from 101 consecutive patients who underwent ‘zero ischaemia’, sutureless LPN were collected in a prospectively maintained database.
• ? Inclusion criteria were tumour size ≤4 cm, predominant exophytic growth and intraparenchymal depth ≤1.5 cm, with a minimum distance of 5 mm from the urinary collecting system.
• ? Hilar vessels were not isolated, tumour dissection was performed with 10‐mm LigaSure^TM (Covidien, Boulder, CO, USA) and haemostasis was performed with coagulation and biological haemostatic agents without reconstructing the renal parenchyma.
• ? Clinical, perioperative and follow‐up data were collected prospectively, and modifications of functional outcome variables were analysed using the paired Wilcoxon test.

RESULTS

• ? The median (range) tumour size was 2.4 (1.5–4) cm, and the median (range) intraparenchymal depth was 0.7 (0.4–1.4) cm.
• ? Hilar clamping was not necessary in any patient, and suture was performed in four patients to ensure complete haemostasis. The median (range) operation duration was 60 (45–160) min, and median (range) intraoperative blood loss was 100 (20–240) mL.
• ? Postoperative complications included fever (n= 4), low urinary output (n= 3) and haematoma, which was treated conservatively (n= 2). The median (range) hospital stay was 3 (2–5) days. The pathologist reported 30 benign tumours and renal cell carcinoma in 71 cases (pT1a in 69 patients, and pT1b in two patients).
• ? At a median follow‐up of 57 months, one patient underwent radical nephrectomy for ipsilateral recurrence. The 1‐year median (range) decrease of split renal function at renal scintigraphy was 1 (0–5) %.

CONCLUSIONS

• ? Zero ischaemia LPN is a reasonable approach to treating small and peripheral tumours, and a sutureless procedure is feasible in most cases.
• ? This technique has a low complication rate and provides excellent functional outcome without impairing oncological results.

     

Partial nephrectomy in two patients with known T3a tumours involving the renal vein

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Although nephron‐sparing surgery (NSS) has became accepted therapy for T1 tumours, radical nephrectony is considered the best therapy for T3a tumours involving the renal vein. NSS can be considered in T3a or greater tumours if imperative indications exist, such as bilateral disease or solitary kidney. However, there is little published data on the characteristics of these patients, the impact of surgery on their renal function, and long‐term oncologic outcomes. This study profiles single‐institution experience with nephron‐sparing surgery for known T3a tumours involving the renal vein, including patient characteristics, tumour characteristics, preoperative and follow‐up imaging, preoperative and follow‐up estimated glomerular filtration rate, length of temporary postoperative haemodialysis, and oncologic outcome. Additionally, we compare this to other published data on nephron‐sparing surgery for similar tumors.

OBJECTIVE

• ? To present two patients with T3a tumours involving the renal vein who underwent nephron‐sparing surgery (NSS) for imperative reasons.

PATIENTS AND METHODS

• ? Retrospective chart review of patients who underwent NSS for renal cell carcinoma (RCC) with known renal vein tumour thrombus (RVTT).
• ? Both patients underwent open partial nephrectomy and renal vein thrombectomy of a solitary kidney.
• ? Primary outcomes of the study include radiographic evidence of recurrence, haemodialysis requirement and estimated glomerular filtration rate (eGFR) before and after surgery.

RESULTS

• ? Patient 1 is 24 months from NSS and has no evidence of recurrence based on CT scan. His final pathology revealed a 9‐cm, T3a, clear cell, Fuhrman grade II carcinoma. He spent 42 days on haemodialysis and is now off all dialysis. His preoperative and most recent eGFR are 48 and 23 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation and 69.4 and 29.8 mL/min by the Cockcroft–Gault equation.
• ? Patient 2 is 9 months from NSS and has no evidence of recurrence based on CT scan. Her final pathology revealed a 6‐cm, T3a, clear cell, Fuhrman grade II–III carcinoma. She spent 30 days on haemodialysis and is now off all dialysis. Her preoperative and most recent eGFR are 58 and 30 mL/min/1.73 m² based on the MDRD equation and 62.2 and 32.8 mL/min by the Cockcroft–Gault equation.

CONCLUSION

• ? Based on our review, preservation of renal function and favourable oncological outcome can be accomplished with NSS in patients with known stage T3a RCC with RVTT and should be considered in carefully selected patients.

     

Positive surgical margins are a risk factor for significant biochemical recurrence only in intermediate-risk disease

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Positive surgical margins (PSMs) after radical prostatectomy are common, although their impact on the risk of disease recurrence is unknown. We examined the impact of PSMs on the risk of ‘significant’ biochemical recurrence stratified by their risk of occult metastatic disease. We find that only in intermediate‐risk disease does the presence of a PSM have a significant impact on the risk of recurrence, and this represents a failure of technique. By contrast, for high‐ and low‐risk disease, the risk of recurrence is driven by intrinsic tumour biology, and the presence of a PSM has little impact on outcome.

OBJECTIVE

• ? To determine the impact of surgical margin status on the risk of significant biochemical recurrence (prostate‐specific antigen [PSA] doubling time <3, <6 or <9 months) after prostatectomy.

MATERIALS AND METHODS

• ? Patients undergoing radical prostatectomy with complete clinical and pathological data and detailed PSA follow‐up were identified from two prospectively recorded databases.
• ? Patients were stratified according to their risk of occult systemic disease (low risk: PSA < 10 ng/dL, pT2 stage and Gleason score ≤6; intermediate risk: PSA 10–20 ng/dL, pT2 stage and/or Gleason score 7; high: PSA > 20 ng/dL or pT3‐4 stage or Gleason score 8–10) and the impact of a positive surgical margin (PSM) within each stratum determined by univariable and multivariable analysis.

RESULTS

• ? Of 1514 patients identified, 276 (18.2%), 761 (50.3%) and 477 (31.5%) were classified as having low‐, intermediate‐ and high‐risk disease respectively.
• ? A total of 370 (24.4%) patients had a PSM and with a median follow‐up of 22.2 months, and 165 (7%) patients had a biochemical recurrence.
• ? Sufficient PSA data was available to calculate PSA doubling times in 151/165 patients (91.5%).
• ? The PSM rate rose significantly, from 11% in low‐risk to 43% in high‐risk disease (P < 0.001), with similar positive associations noted with tumour grade, stage and serum PSA (P < 0.001).
• ? Patients with low‐risk disease had essentially identical risks of significant biochemical recurrence over the study period, regardless of surgical margin status. By contrast, in patients with both intermediate‐ and high‐risk disease, a PSM was a strong predictor of significant biochemical recurrence on univariable analysis. On multivariable analysis, howver, PSM predicted significant disease recurrence in intermediate‐risk disease only.

CONCLUSIONS

• ? PSM is a risk factor for significant biochemical recurrence only in intermediate risk disease.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

Study Type – Diagnostic (case series) Level of Evidence 4

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.