Postoperative surveillance for renal cell carcinoma: a multifactorial histological subtype specific protocol

OBJECTIVE

To create a model that adjusts surveillance after surgery to the natural history of surgically treated renal cell carcinoma (RCC), and to assess the cost of several surveillance models with a long‐term longitudinal follow‐up, as although there are many models for predicting the outcome in RCC, most surveillance protocols remain based primarily on stage alone, and thus might be inaccurate as they do not incorporate many other pathological features that have a significant effect on recurrence.

PATIENTS AND METHODS

We identified 1864, 357 and 118 patients with pM0 clear cell, papillary and chromophobe RCC, respectively, who had a a radical or partial nephrectomy between 1970 and 2000. All recurrences were classified according to location (abdomen, thorax, bone, brain). Cox proportional hazards models were used to determine which pathological features were independently predictive of recurrence in each group. Three subtype‐specific protocols were devised based on site‐specific recurrence rates.

RESULTS

Positive surgical margins, the 2002 Tumour‐Node‐Metastasis classification, size, nuclear grade, and histological tumour necrosis were independently associated with abdominal recurrence in patients with clear‐cell RCC. These same features, except for surgical margins, were significantly associated with thoracic recurrence. The 2002 classification and nuclear grade were independently associated with abdominal and thoracic recurrence in patients with papillary RCC. No multivariate analysis was done for chromophobe RCC as there were only 10 recurrences to the abdomen and three to the thoracic region. However, these patients were stratified according to stage and grade, as recurrences in this group had a clear stage‐ and grade‐specific pattern.

CONCLUSIONS

We present a subtype‐specific multifactorial surveillance protocol based on significant predictors of recurrence. This protocol is better than algorithms based on stage alone and can be used to effectively tailor postoperative imaging to the individual patient.     

Neoadjuvant therapy for localized and locally advanced renal cell carcinoma

Neoadjuvant Targeted Molecular Therapy in the setting of localized and locally advanced renal cell carcinoma has emerged as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. Presurgical tumor reduction has been demonstrated in a number of studies including a recently published randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Nonetheless, most reports are small phase II clinical trials or retrospective reports. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for neoadjuvant strategies. This article reviews the current status and future prospects of neoadjuvant therapy in nonmetastatic renal cell carcinoma.     

Guidelines for the surveillance of localized renal cell carcinoma based on the patterns of relapse after nephrectomy

PURPOSE: We characterized relapse patterns in patients with sporadic renal cell carcinoma (RCC) following radical and partial nephrectomy, and developed surveillance guidelines. MATERIALS AND METHODS: Between 1989 and 2000, 495 patients underwent nephrectomy for RCC at 1 of 5 Canadian referral centers. Median followup was 42 months. RESULTS: The rate of relapse, time to relapse and site of relapse were associated with pathological stage. Five-year progression-free probability was 93% for pT1, 81% for pT2, 67% for pT3A and 57% for pT3B (p <0.001). Compared to patients with pT1-2 those with pT3A-B lesions had earlier relapse after nephrectomy (median 12 vs 26 months, p = 0.001) and were at higher risk for relapse at abdominal sites (14% vs 1.8%, p < 0.001). Abdominal relapse was detected in the absence of symptoms, abnormal biochemical profile or thoracic metastases detectable by chest x-ray in 7 patients (1.4%) overall, including 3 (0.9%) with pT1, 3 (4%) with pT3A and 1 (3%) with pT3B. CONCLUSIONS: The risk and the pattern of relapse of RCC after nephrectomy are associated with pathological stage. For the surveillance of recurrent disease after nephrectomy we recommend annual clinical assessment and chest x-ray in pT1-2 cases. Patients with pT3A-B should be followed every 6 months for the first 3 years with clinical assessment and chest x-ray, and annual followup thereafter. The higher risk of abdominal relapse in patients with pT3A-B indicates that they should receive surveillance abdominal imaging. We recommend abdominal computerized tomography 6, 12, 24 and 36 months postoperatively.     

Benign pathological findings in 303 Chinese patients undergoing surgery for presumed localized renal cell carcinoma

Objective: To analyze the incidence of benign lesions in Chinese patients undergoing nephrectomies for renal masses identified as localized renal cell carcinoma (RCC) in preoperative imaging. Methods: Between 1999 and 2007, 303 patients (112 female, 191 male) with presumed localized RCC underwent nephrectomy (234 radical nephrectomies and 69 partial nephrectomies). Preoperative computed tomography images and pathological findings were reviewed and analyzed. Results: Pathological examinations revealed 31 (10.2%) benign lesions in the 303 patients. Among these 31 benign lesions, 15 (5.0%) were angiomyolipomas (AML) and only four (1.3%) were oncocytomas. Significantly, 20 (17.9%) of the 112 female patients had benign lesions compared with 11 (5.8%; P = 0.001) male patients. Benign renal lesions were found in five (25.0%) of the 20 patients with renal masses smaller than 2 cm, 13 (13.0%) of the 100 patients with renal masses 2–4 cm in size and 13 (7.1%) of the 183 patients with renal masses larger than 4 cm. Conclusions: Patients in the present study population show a low incidence of benign renal lesions, approximately half of them being AML. Female patients and patients with renal masses smaller than 4 cm are more likely to have benign renal lesions.     

Guideline of guidelines: follow‐up after nephrectomy for renal cell carcinoma

The purpose of this article was to review and compare the international guidelines and surveillance protocols for post‐nephrectomy renal cell carcinoma (RCC). PubMed database searches were conducted, according to the PRISMA statement for reporting systematic reviews, to identify current international surveillance guidelines and surveillance protocols for surgically treated and clinically localized RCC. A total of 17 articles were reviewed. These included three articles on urological guidelines, three on oncological guidelines and 11 on proposed strategies. Guidelines and strategies varied significantly in relation to follow‐up, specifically with regard to the frequency and timing of radiological imaging. Although there is currently no consensus within the literature regarding surveillance protocols, various guidelines and strategies have been developed using both patient and tumour characteristics.     

Evaluation of the intact specimen after laparoscopic radical nephrectomy for clinically localized renal cell carcinoma identifies a subset of patients at increased risk for recurrence

PURPOSE: Laparoscopic radical nephrectomy (LRN) is emerging as a standard approach for low stage renal cell carcinoma (RCC). Some suggest that specimen morcellation for extraction results in less morbidity and a faster recovery. However, morcellation may preclude accurate pathological staging and may hinder precise pathological grading. With pathological evaluation of an intact specimen we identified patients harboring high risk disease that was not anticipated preoperatively, defined as pT2 high grade (G3-4) or lesions greater than pT2. MATERIALS AND METHODS: We retrospectively reviewed the records of 192 patients who underwent LRN for renal lesions at The University of Texas M. D. Anderson Cancer Center between April 2002 and April 2004. RESULTS: A total of 192 patients underwent LRN for presumed RCC. In all cases specimens were removed intact. Of these cases 137 were cT1/T2 N0 M0 and had a final pathological diagnosis of RCC. All surgical margins were negative. Of the 137 patients 40 (29.2%) were at increased risk for recurrence based on high risk features. Specifically up staging from cT1-2 to pT3 disease occurred in 30 patients (21.9%) while 12 patients (8.8%) were found to have pT2 G3-4 disease. All 40 patients with high risk disease underwent more intensive surveillance and 17 (43%) participated in adjuvant systemic therapy trials. CONCLUSIONS: In our study 21.9% of patients with clinical T1-2 disease were pathologically up staged and 29.2% were identified as being at high risk for recurrence after intact specimen extraction for localized RCC. These patients are candidates for more intensive followup treatment and may benefit from enrollment in adjuvant therapy protocols.     

Unclassified renal cell carcinoma: clinical features and prognostic impact of a new histological subtype

PURPOSE: We characterized the histopathological features and clinical behavior of unclassified renal cell carcinoma and compared the prognostic outcome in patients with unclassified and conventional (clear cell) renal cell carcinoma. MATERIALS AND METHODS: A total of 31 patients with unclassified renal cell carcinoma are included in the kidney cancer database at our institution. Another 317 matched patients with clear cell carcinoma were used for comparing demographic, clinical, pathological and survival data. RESULTS: The incidence of unclassified renal cell carcinoma was 2.9%. At initial diagnosis 29 patients (94%) with unclassified and 264 (83%) with clear cell renal cell carcinoma had metastatic disease (p = 0.143). Compared with the clear cell variety unclassified disease was associated with larger tumors (p = 0.005), increased risk of adrenal gland involvement (25% of cases, p = 0.0001), direct invasion to adjacent organs (42%, p = 0.00001), bone (52%, p = 0.022), regional (52%, p = 0.0042) and nonregional lymph node (41%, p = 0.03) metastases. Nephrectomy was less likely to be attempted or completed in unclassified renal cell carcinoma cases (61%, p = 0.00007). Unclassified histology was a significant indicator for poor prognosis on multivariate analysis (p <0.0001). Median survival in patients with unclassified renal cell carcinoma was 4.3 months. Nephrectomy alone did not confer any survival advantage in these cases (p = 0.1086), while immunotherapy did (p = 0.008). The combination of nephrectomy and immunotherapy yielded improved survival over immunotherapy alone (p = 0.0356) but patients with unclassified renal cell carcinoma were significantly less likely than those with clear cell disease to be eligible for immunotherapy regimens (p = 0.05). CONCLUSIONS: Unclassified renal cell carcinoma is associated with distinct and highly aggressive biological behavior, and poor clinical outcome. Whenever feasible, immunotherapy with nephrectomy is warranted.     

非转移性肾细胞癌的术前危险分层

目的 探讨建立一种非转移性肾细胞癌(RCC)术前危险因素的评价模型. 方法 回顾性分析了3个中心实施手术治疗的363例非转移性RCC患者资料,Cox比例风险模型进行单因素和多因素分析,评价影响患者生存期的临床以及病理变量,并建立再现风险公式(RRF). 结果 363例平均随访46个月,2年及5年总体生存率为90%(326/363)及54%(196/363),术后复发71例.Cox单因素分析中4个变量对预后有影响,即临床表现(RR=50.583,P=0.000)、肿瘤大小(RR=104.018,P-0.000)、肿瘤分期(RR-135.145,P=0.000)、分级(RR=86.397,P=0.000).Cox多因素分析中,临床表现(RR=6.946,P=0.008)、肿瘤大小(RR=9.353,P=0.002)、分期(RR=69.580,P=0.000)、分级(RR=15.363,P=0.000)仍然对预后具有明显影响.通过Cox多因素分析结果建立了RRF(0.530×临床表现+0.749×肿瘤大小).等式分组后,RRF≤1.3组的2年及5年生存率为100.0%(147例)及71.3%(105例),RRF＞1.3组的2年及5年生存率为82.8%(179例)、38.1%(82例),2组预后差异有统计学意义(P＜0.01). 结论 建立了一个独立于分期、分级,仅使用术前变量对非转移性RCC危险分层的公式.RRF有助于术前判断患者预后以及实施个体化随访和辅助治疗方案.     

Associations with contralateral recurrence following nephrectomy for renal cell carcinoma using a cohort of 2,352 patients

PURPOSE: We determined the incidence of and factors associated with the development of renal cell carcinoma (RCC) in the contralateral kidney after nephrectomy for localized RCC. MATERIALS AND METHODS: Between 1970 and 2000, 2,352 patients with sporadic, localized unilateral RCC and a normal contralateral kidney underwent nephrectomy for RCC. Cancer specific survival rates were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were used to determine associations with outcome. RESULTS: Of the 2,352 patients studied 28 (1.2%) had RCC in the contralateral kidney, including 20 with clear cell and 8 with papillary RCC. Mean time from primary surgery to contralateral recurrence was 5.2 years (median 4.8, range 0 to 18) for clear cell RCC compared with 5.6 years (median 1.3, range 0 to 21) for papillary cell RCC. Positive surgical margins (risk ratio 14.23, p = 0.010) and multifocality (risk ratio 5.74, p = 0.019) were significantly associated with contralateral recurrence following nephrectomy for clear cell RCC, while nuclear grade (risk ratio for grades 3/4 vs 1/2, 4.78, p = 0.040) was significantly associated with contralateral recurrence following nephrectomy for papillary RCC. In patients with clear cell RCC estimated cancer specific survival rates 1, 3, and 5 years following contralateral recurrence were 93.8%, 80.2% and 72.9%, respectively. CONCLUSIONS: In patients with localized RCC and a normal contralateral kidney who underwent nephrectomy for RCC positive surgical margins and multifocality were significant predictors of contralateral recurrence for clear cell RCC, while nuclear grade was a significant predictor of contralateral recurrence for papillary RCC.     

Nephrectomy improves the survival of patients with locally advanced renal cell carcinoma

OBJECTIVES

To examine the cancer‐specific survival of patients treated with nephrectomy and compared it to that of patients managed without surgery.

PATIENTS AND METHODS

Of 43 143 patients with renal cell carcinoma (RCC) identified in the 1988–2004 Surveillance, Epidemiology and End Results database, 7068 had locally advanced RCC and with no distant metastasis. These patients had a nephrectomy (6786, 96.0%) or no surgical therapy (282, 4.0%). Multivariable Cox regression models, and matched and unmatched Kaplan‐Meier survival analyses, were used to compare the effect of nephrectomy vs non‐surgical therapy on cancer‐specific survival. Also, competing‐risks regression models adjusted for the effect of other‐cause mortality. Covariates and matching variables consisted of age, gender, tumour size and year of diagnosis.

RESULTS

The 1‐, 2‐, 5‐ and 10‐year cancer‐specific survival of patients who had nephrectomy was 88.9%, 88.1%, 68.6% and 57.5%, vs 44.8%, 30.6%, 14.5% and 10.6% for non‐surgical therapy. In multivariable analyses, relative to nephrectomy, non‐surgical therapy was associated with a 5.8‐fold higher rate of cancer‐specific mortality (P < 0.001). Non‐surgical therapy was also associated with a 5.1‐fold higher rate of cancer‐specific mortality in matched analyses (P < 0.001). Finally, competing‐risks regression confirmed the statistical significance of the variable defining treatment type (nephrectomy vs non‐surgical therapy) in multivariable and matched analyses (P < 0.001).

CONCLUSION

Relative to non‐surgical treatment, nephrectomy improves the cancer‐specific survival of patients with locally advanced RCC; our findings await prospective confirmation.     

Oncological outcome of 100 laparoscopic radical nephrectomies for clinically localized renal cell carcinoma

BACKGROUND: Laparoscopic renal surgery is now accepted within the urological community and its indication is extended to oncological operation. The oncological outcome and survival of patients undergoing laparoscopic radical nephrectomy for clinically localized renal cell carcinoma were evaluated. METHODS: From October 1998 to July 2003, 100 patients underwent laparoscopic radical nephrectomy for clinically localized renal cell carcinoma. All operations were performed by transperitoneal approach with early vascular control. Perioperative events and pathological data were recorded prospectively. Patients were followed up by clinical examination, chest radiograph, ultrasonography and/or computed tomography where appropriate. RESULTS: The median age of patients was 61 years. Median operating time was 120 min and blood loss was 100 mL. There were five open conversions. There was no perioperative mortality but 11 patients had complications. Resection margins were clear in all but one patient. The median tumour size was 4.6 cm. The median follow-up time was 30 months. All patients survived up to the date of review. No patient developed port-site recurrence but two patients had recurrence at the renal bed 1 year after the operation. Five patients developed distant metastases involving liver, lung and bone. CONCLUSION: Laparoscopic radical nephrectomy is a safe and efficacious treatment option for clinically localized renal cell carcinoma. The intermediate-term oncological outcome appears favourable.     

基于肾单位精细解剖的后腹腔镜肾部分切除术方法改进与应用

目的：探索基于肾单位精细解剖的后腹腔镜保留肾单位肾部分切除的手术方法和技巧,借助解剖方法减少出血和尿瘘的可能性。方法：我院2012年1～12月期间住院的肾脏肿瘤患者31例,男19例,女12例,年龄28468岁,平均（56．1±13．8）岁。肿瘤直径1．2～6．0cm,平均（3．4±0．7）cm。术中阻断肾动脉后,距肿瘤边缘3～5mm剪开肾包膜及肾皮质,在肾实质的切口内,沿肾锥体髓放线钝性加锐性向深处和基底分离,使包裹一层肾髓质的瘤体与保留的肾脏髓质分开,显露出的基底部的血管应用双极电凝后剪断。仔细剥离肾小盏,以可吸收线两层缝合,关闭肾脏创面。记录动脉阻断时间、手术时间、术中出血量、术后引流量、病理结果和手术并发症。结果：本组31例患者采用切开包膜实质剥离髓质方法均获成功。其中19例可见基底部1支血管,8例可见2支血管,19例可见肾盏。平均手术时间（95．5±27．1）min;平均术中动脉阻断时间（21．2±7．2）min;平均术中出血量（55．7±18．9）ml;平均术后引流量（92．3±28．9）ml,平均术后住院时间（6．1±0．6）d;术后无继发出血、漏尿等并发症发生。所有标本呈完整楔形块状,切缘均为阴性。术后病理证实：肾透明细胞癌27例、嗜酸细胞腺瘤1例、肾小球旁细胞瘤1例、嫌色细胞癌2例。TNM分期：T1a期28例,T1b期3例。结论：采用切开包膜和实质剥离肾髓质改良的后腹腔镜保留肾单位肾部分切除术,切除瘤体部所附着肾组织确切完整,有利于切缘阴性。基底部止血确实,处理累及的肾盏确切,可以减少术后继发出血及漏尿的发生。