World J Urol DOI 10.1007/s00345-014-1390-6
Original Article
The blind spots in follow-up after nephrectomy or nephron-sparing surgery for localized renal cell carcinoma Tim J. van Oostenbrugge · Stephanie G. C. Kroeze · J. L. H. Ruud Bosch · Harm H. E. van Melick
Received: 23 May 2014 / Accepted: 22 August 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose This study was conducted to identify time to and type of recurrence in relation to scheduled follow-up (FU) imaging after nephrectomy or nephron-sparing surgery for localized renal cell carcinoma (RCC). Using this information, future guidelines could improve the early detection of metastases. Methods Measured from moment of treatment, all recurrences after (partial) nephrectomy performed between 2000 and 2010 were categorized as being detected early (5 year for T1/T2 and >10 year for T3/T4), or intermediate (time within those two) based on European Association of Urology (EAU) guidelines. Also symptomatic presentation was screened. Results Recurrent disease developed in 80 of 396 patients after (partial) tumor nephrectomy. Mean time to recurrence in months was 56 (n = 21) for T1, 24 (n = 18) for T2, 21 (n = 38) for T3, and 11 (n = 2) for T4 tumors. Detection of Preliminary data presented on AUA annual meeting 2013, San Diego. T. J. van Oostenbrugge (*) Department of Urology, Radboud University Medical Center, P.O. box 9101, 6525 GA Nijmegen, The Netherlands e-mail: [email protected] S. G. C. Kroeze Department of Urology, Jeroen Bosch Hospital, ’s Hertogenbosch, The Netherlands J. L. H. R. Bosch Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands H. H. E. van Melick Department of Urology, St Antonius Hospital, Utrecht/Nieuwegein, The Netherlands
early recurrence occurred in 22 patients (28 %), of which 20 (91 %) were T2–T4 tumors. In 10 (48 %) of T1 tumors, late recurrence was found. Of the patients with symptoms due to recurrence, 65 % (17/26) were detected outside the FU surveillance protocol (P = 0.01). Conclusion A more intensive FU the first 6 months after nephrectomy for T2–T4 and FU imaging ≥5 years after surgery for T1 tumors might improve early and asymptomatic detection of recurrent disease after nephrectomy for RCC. Keywords Renal cell carcinoma · Follow-up · Surveillance · Recurrence · Metastasis
Introduction About 2–3 % of newly diagnosed cancer is renal cell carcinoma (RCC) [1]. During the past two decades, the mortality rate due to RCC has stabilized or declined in most European countries and in the USA [2, 3]. With the increase of cross-sectional imaging, the number of incidentally diagnosed RCCs that are smaller and of lower stage has been growing [4, 5]. These tumors tend to metastasize less often compared with higher-stage tumors, and metastasis are more frequently found after longer follow-up (FU) [6]. This changing face of RCC has led to discussions about the FU after treatment of RCC. The rationale behind the FU after nephrectomy is early detection of local recurrence and distant metastasis based on the presumption that early diagnosis improves the outcomes of additional therapeutic options due to less extended tumor growth [7, 8]. The surveillance after partial or radical nephrectomy for RCC currently depends on anatomical, clinical, and histologic characteristics of the resected tumor [9]. However,
13
what the preferred surveillance algorithm should be remains unclear. Therefore, only proposed algorithms for surveillance after nephrectomy for RCC based on prognostic nomograms that have been developed in the European and American guidelines are available, leaving much to the discretion of the treating urologist [7, 8]. The objective of this study was to compare two types of metastases: first, metastases that were detected by imaging performed on scheduled FU imaging (guideline scheme), and second, metastases detected at other moments than defined by this scheme. We thereby aimed to identify patients prone to earlier and asymptomatic detection.
Methods Patient selection All patients aged older than 18 who underwent a (partial) nephrectomy of a nontransplanted kidney for RCC from January 2000 until December 2010 in two separate clinics in the Netherlands (St. Antonius Hospital Utrecht–Nieuwegein and University Medical Center Utrecht) were reviewed. Exclusion criteria were positive lymph nodes reported in pathological report following surgery, death during operation or before discharge from the hospital, or when patient files were lost.
World J Urol
good condition at the time of reviewing the patient’s file. Causes of death could be cancer-related or unrelated to the disease. Recurrent disease was defined as diagnosis of local recurrence or distant metastasis. Local recurrence was defined as new tumor formation in a partially resected kidney or local recurrence in the renal sinus after radical nephrectomy. In accordance with the European Association of Urology (EAU) and American Urological Association (AUA) guidelines on proposed FU imaging algorithms, the first FU imaging was performed within 6 months after (partial) nephrectomy [7, 8]. Thereafter, FU imaging of the abdomen and thorax was performed at least 2 times a year. FU imaging was at least performed up to 5 years after surgery for T1 and T2, and up to 10 years for T3 and T4 tumors. Therefore, based on guidelines, recurrences were classified as follows: ≤6 months from initial treatment early, within 6–60 months for T1/T2, 6–120 months for T3/T4 intermediate, >60 months for T1/T2, and >120 months for T3/T4 as late. The imaging modality used was left to the discretion of the treating urologist. Whether recurrent disease was diagnosed by scheduled FU imaging or by evaluation of symptoms (asymptomatic vs. symptomatic presentation) was determined. Statistical analysis
Data extraction Data on demographics, initial nephrectomy, tumor characteristics, tumor staging, and FU were recorded. In case of recurrent disease, whether routine FU imaging or evaluation of the patient’s symptoms had resulted in the diagnosis of recurrence was determined.
For statistical analysis, SPSS 19.0 software (SPSS/IBM Corp, Armonk, NY) was used. Group comparison was done using a χ2 test. Survival analysis was done using Kaplan– Meier analysis. A P value of ≤0.05 was considered to indicate a statistically significant difference.
Initial staging and treatment
Results
Staging at presentation was done using at least a contrastenhanced computed tomography (CT) scan of the abdomen (magnetic resonance imaging was performed if CT was contraindicated) and a chest X-ray. In case of suspicion of at least a T3 tumor, a contrast-enhanced CT scan of the thorax was performed. If feasible, an open partial nephrectomy was performed in case of T1 tumors. If not feasible and in case of larger tumors, open or laparoscopic radical nephrectomy was performed. From 2005, a progressive number of radical nephrectomies were performed laparoscopically.
Patient flow
FU analysis
Demographics
Duration of FU was calculated from the date of nephrectomy to the date of death or the last medical check-up with
Data on demographics, initial nephrectomy, tumor characteristics, and staging are listed in Table 1.
13
A total of 461 nephrectomies were reviewed, and 15 patients were excluded. Two patients had positive lymph nodes, 11 patients died before discharge from the hospital, and files of two patients were lost. Of the 446 included nephrectomies, 22 patients were eventually lost to FU, and synchronous metastasis occurred in 50. Metastasis developed in 80 (20 %) of the 396 patients remaining for analysis during a mean ± standard deviation FU of 66 ± 39 months.
World J Urol Table 1 Patient and tumor characteristics Total cohort (n = 396)
Patient with recurrent disease (n = 80)
No. (%) or Mean ± SD
No. (%) or Mean ± SD
Unclassified
54 (68) 64 ± 10 34 (43) 21 (27) 18 (23) 38 (48) 2 (3) 1 (1)
T stage I II III IV
Initial staging (n = 396)
Recurrence (n = 80)
Months from nephrectomy to recurrence
No. (% total cohort)
No. (% per T stage)
Mean ± SD
231 (58) 70 (18) 90 (23) 3 (0.5)
21 (9) 18 (26) 38 (42) 2 (67)
56 ± 39 24 ± 25 21 ± 22 11 ± 8
2 (0.5)
1 (50)
Unknown
SD Standard deviation
4.90 ± 1.35 10.40 ± 3.50 9.03 ± 2.20 11.00 ± 2.12
1.0
P 10 years from nephrectomy ‡
1 case missing data about T stage and therefore was not evaluated
Symptomatic versus asymptomatic patients Data on the diagnosis of the metastasis were not available for two patients, in the other 78 patients, 26 (33 %) recurrences were symptomatic at time of diagnosis, and 52 (67 %) were detected by routine FU imaging. Of the 26 symptomatic patients, 17 (65 %) were detected outside the recommended FU surveillance protocol (P = 0.01). Of the 22 early detected patients (≤6 months from nephrectomy), 8 (36 %) were symptomatic at presentation (P = 0.74). Of the 13 metastases detected after the proposed FU duration, 9 (69 %) caused symptoms at presentation (P
Original Article
The blind spots in follow-up after nephrectomy or nephron-sparing surgery for localized renal cell carcinoma Tim J. van Oostenbrugge · Stephanie G. C. Kroeze · J. L. H. Ruud Bosch · Harm H. E. van Melick
Received: 23 May 2014 / Accepted: 22 August 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose This study was conducted to identify time to and type of recurrence in relation to scheduled follow-up (FU) imaging after nephrectomy or nephron-sparing surgery for localized renal cell carcinoma (RCC). Using this information, future guidelines could improve the early detection of metastases. Methods Measured from moment of treatment, all recurrences after (partial) nephrectomy performed between 2000 and 2010 were categorized as being detected early (5 year for T1/T2 and >10 year for T3/T4), or intermediate (time within those two) based on European Association of Urology (EAU) guidelines. Also symptomatic presentation was screened. Results Recurrent disease developed in 80 of 396 patients after (partial) tumor nephrectomy. Mean time to recurrence in months was 56 (n = 21) for T1, 24 (n = 18) for T2, 21 (n = 38) for T3, and 11 (n = 2) for T4 tumors. Detection of Preliminary data presented on AUA annual meeting 2013, San Diego. T. J. van Oostenbrugge (*) Department of Urology, Radboud University Medical Center, P.O. box 9101, 6525 GA Nijmegen, The Netherlands e-mail: [email protected] S. G. C. Kroeze Department of Urology, Jeroen Bosch Hospital, ’s Hertogenbosch, The Netherlands J. L. H. R. Bosch Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands H. H. E. van Melick Department of Urology, St Antonius Hospital, Utrecht/Nieuwegein, The Netherlands
early recurrence occurred in 22 patients (28 %), of which 20 (91 %) were T2–T4 tumors. In 10 (48 %) of T1 tumors, late recurrence was found. Of the patients with symptoms due to recurrence, 65 % (17/26) were detected outside the FU surveillance protocol (P = 0.01). Conclusion A more intensive FU the first 6 months after nephrectomy for T2–T4 and FU imaging ≥5 years after surgery for T1 tumors might improve early and asymptomatic detection of recurrent disease after nephrectomy for RCC. Keywords Renal cell carcinoma · Follow-up · Surveillance · Recurrence · Metastasis
Introduction About 2–3 % of newly diagnosed cancer is renal cell carcinoma (RCC) [1]. During the past two decades, the mortality rate due to RCC has stabilized or declined in most European countries and in the USA [2, 3]. With the increase of cross-sectional imaging, the number of incidentally diagnosed RCCs that are smaller and of lower stage has been growing [4, 5]. These tumors tend to metastasize less often compared with higher-stage tumors, and metastasis are more frequently found after longer follow-up (FU) [6]. This changing face of RCC has led to discussions about the FU after treatment of RCC. The rationale behind the FU after nephrectomy is early detection of local recurrence and distant metastasis based on the presumption that early diagnosis improves the outcomes of additional therapeutic options due to less extended tumor growth [7, 8]. The surveillance after partial or radical nephrectomy for RCC currently depends on anatomical, clinical, and histologic characteristics of the resected tumor [9]. However,
13
what the preferred surveillance algorithm should be remains unclear. Therefore, only proposed algorithms for surveillance after nephrectomy for RCC based on prognostic nomograms that have been developed in the European and American guidelines are available, leaving much to the discretion of the treating urologist [7, 8]. The objective of this study was to compare two types of metastases: first, metastases that were detected by imaging performed on scheduled FU imaging (guideline scheme), and second, metastases detected at other moments than defined by this scheme. We thereby aimed to identify patients prone to earlier and asymptomatic detection.
Methods Patient selection All patients aged older than 18 who underwent a (partial) nephrectomy of a nontransplanted kidney for RCC from January 2000 until December 2010 in two separate clinics in the Netherlands (St. Antonius Hospital Utrecht–Nieuwegein and University Medical Center Utrecht) were reviewed. Exclusion criteria were positive lymph nodes reported in pathological report following surgery, death during operation or before discharge from the hospital, or when patient files were lost.
World J Urol
good condition at the time of reviewing the patient’s file. Causes of death could be cancer-related or unrelated to the disease. Recurrent disease was defined as diagnosis of local recurrence or distant metastasis. Local recurrence was defined as new tumor formation in a partially resected kidney or local recurrence in the renal sinus after radical nephrectomy. In accordance with the European Association of Urology (EAU) and American Urological Association (AUA) guidelines on proposed FU imaging algorithms, the first FU imaging was performed within 6 months after (partial) nephrectomy [7, 8]. Thereafter, FU imaging of the abdomen and thorax was performed at least 2 times a year. FU imaging was at least performed up to 5 years after surgery for T1 and T2, and up to 10 years for T3 and T4 tumors. Therefore, based on guidelines, recurrences were classified as follows: ≤6 months from initial treatment early, within 6–60 months for T1/T2, 6–120 months for T3/T4 intermediate, >60 months for T1/T2, and >120 months for T3/T4 as late. The imaging modality used was left to the discretion of the treating urologist. Whether recurrent disease was diagnosed by scheduled FU imaging or by evaluation of symptoms (asymptomatic vs. symptomatic presentation) was determined. Statistical analysis
Data extraction Data on demographics, initial nephrectomy, tumor characteristics, tumor staging, and FU were recorded. In case of recurrent disease, whether routine FU imaging or evaluation of the patient’s symptoms had resulted in the diagnosis of recurrence was determined.
For statistical analysis, SPSS 19.0 software (SPSS/IBM Corp, Armonk, NY) was used. Group comparison was done using a χ2 test. Survival analysis was done using Kaplan– Meier analysis. A P value of ≤0.05 was considered to indicate a statistically significant difference.
Initial staging and treatment
Results
Staging at presentation was done using at least a contrastenhanced computed tomography (CT) scan of the abdomen (magnetic resonance imaging was performed if CT was contraindicated) and a chest X-ray. In case of suspicion of at least a T3 tumor, a contrast-enhanced CT scan of the thorax was performed. If feasible, an open partial nephrectomy was performed in case of T1 tumors. If not feasible and in case of larger tumors, open or laparoscopic radical nephrectomy was performed. From 2005, a progressive number of radical nephrectomies were performed laparoscopically.
Patient flow
FU analysis
Demographics
Duration of FU was calculated from the date of nephrectomy to the date of death or the last medical check-up with
Data on demographics, initial nephrectomy, tumor characteristics, and staging are listed in Table 1.
13
A total of 461 nephrectomies were reviewed, and 15 patients were excluded. Two patients had positive lymph nodes, 11 patients died before discharge from the hospital, and files of two patients were lost. Of the 446 included nephrectomies, 22 patients were eventually lost to FU, and synchronous metastasis occurred in 50. Metastasis developed in 80 (20 %) of the 396 patients remaining for analysis during a mean ± standard deviation FU of 66 ± 39 months.
World J Urol Table 1 Patient and tumor characteristics Total cohort (n = 396)
Patient with recurrent disease (n = 80)
No. (%) or Mean ± SD
No. (%) or Mean ± SD
Unclassified
54 (68) 64 ± 10 34 (43) 21 (27) 18 (23) 38 (48) 2 (3) 1 (1)
T stage I II III IV
Initial staging (n = 396)
Recurrence (n = 80)
Months from nephrectomy to recurrence
No. (% total cohort)
No. (% per T stage)
Mean ± SD
231 (58) 70 (18) 90 (23) 3 (0.5)
21 (9) 18 (26) 38 (42) 2 (67)
56 ± 39 24 ± 25 21 ± 22 11 ± 8
2 (0.5)
1 (50)
Unknown
SD Standard deviation
4.90 ± 1.35 10.40 ± 3.50 9.03 ± 2.20 11.00 ± 2.12
1.0
P 10 years from nephrectomy ‡
1 case missing data about T stage and therefore was not evaluated
Symptomatic versus asymptomatic patients Data on the diagnosis of the metastasis were not available for two patients, in the other 78 patients, 26 (33 %) recurrences were symptomatic at time of diagnosis, and 52 (67 %) were detected by routine FU imaging. Of the 26 symptomatic patients, 17 (65 %) were detected outside the recommended FU surveillance protocol (P = 0.01). Of the 22 early detected patients (≤6 months from nephrectomy), 8 (36 %) were symptomatic at presentation (P = 0.74). Of the 13 metastases detected after the proposed FU duration, 9 (69 %) caused symptoms at presentation (P
