Laparoscopic and open postchemotherapy retroperitoneal lymph node dissection in patients with advanced testicular cancer – a single center analysis

PCLND plays an important role in the management of patients with advanced seminomatous and NSGCT [1–5]. The technical advances in radiographic staging and the increased use of tumor markers have improved the correct identification of candidates for PCLND [6]. However, even with the introduction of FDG-PET for staging of postchemotherapy seminoma patients we cannot reliably rule out viable disease in residual GCT [7]. Postchemotherapy residual masses in patients suffering from non-seminoma should be resected according to large retrospective series and the most recent urological guidelines [6, 8]. Traditionally, this resection is performed by an open surgical approach (O-PCLND) - a technically demanding procedure which should be limited to experienced tertiary referral centers [9, 10]. The extension of the dissection varies from a radical bilateral approach to a more limited lumpectomy. Full bilateral resection is the standard of care for extensive residual masses. A recent analysis of 152 patients by Heidenreich et al. revealed that in well-defined masses a modified template resection does not worsen oncological outcome, but considerably decreases treatment morbidity [11].

O-PCLND is associated with a significant intra- and postoperative morbidity resulting in prolonged hospital stays frequently. Subramanian and colleagues analyzed 96 O-PCLND patients and reported intraoperative, postoperative and late complications in 12%, 32% and 7% of cases, respectively of which 8% were classified as Clavien Grade III/IV complications [12, 13].

The complication rate of primary laparoscopic retroperitoneal lymph node dissection in stage I GCTs varies widely in the literature with incidences of 2.2-20%, the majority of with are vascular injuries [14]. For L-PCLND complication rates of up to 43.8% have been reported, necessitating a high level of laparoscopic training for its prevention [14, 15]. At the time of L-PCNLD implementation, smaller series with high conversion rates to open surgery have been reported [16]. However, more recent data restricted to small tumors proved that L-PCLND is feasible and has morbidity rates comparable to O-PCLND [17, 18]. So far no study has directly compared intra and postoperative data of L-PCLND patients to a contemporary O-PCLND cohort. Consequently, L-PCLND has not been recommended as a standard surgical approach for patients with residual masses following chemotherapy for advanced testicular cancer [1, 4, 6].

The results obtained for our L-PCLND patients are comparable to those published previously [17–20]. In 2009 Calestroupat and colleagues reported their experience with 26 L-PCLND patients. Median residual tumor diameter was 3.4 cm, while the conversion rate and the transfusion rate were 11.5% and 3.8%, respectively. Median operative time (183 min) was relatively short with a median hospital stay of 5 days. Grade 3/4 complications occurred in 7.6% of cases. The authors concluded that a high level of surgical expertise is needed to successfully perform a L-PCLND. Although L-PCLND has been restricted to patients with small residual tumors in the study of Calestroupat et al., their conversion rate, transfusion rate and the number of Grade3/4 complication were higher compared to our observations [18].

In a series of 49 L-PCLND patients with residual tumor sizes between 2-5 cm Janetschek and co-workers reported a mean operative time of 226 min and a mean postoperative hospital stay of 3.5 days. Overall, complication rate was low. All bleeding complications were managed laparoscopically and no blood transfusion was necessary. Interestingly, L-PCLND was only applied to patients with clinical stage IIb disease, thereby partly explaining these favourable intra- and postoperative results [17].

The largest L-PCLND series of 59 patients was published by Albqami from Linz, Austria. A mean operative time of 234 min, a conversion rate of 0%, a mean estimated blood loss of 165 ml and a mean hospital stay of 3.8 days were reported. During a 5 year follow-up two patients relapsed [19].

In 2008 Steiner et al. demonstrated the feasibility of a bilateral L-PCLND with the preservation of sympathetic nerves in 42 patients (stage IIB n = 19). No conversion to O-PCLND was necessary; mean operative time was 323 min, no intraoperative complications were reported. Antegrade ejaculation was reported for 85.7% of patients. After a mean follow up of 17.2 months no disease recurrence was observed. Unfortunately, there were no exact tumor diameters and locations reported in this study [20]. Comparison to our data is therefore challenging.

Overall, none of the above mentioned studies directly compared L-PCLND patients with a contemporary O-PCLND cohort.

For O-PCLND patients with initial tumor masses larger than 5 cm local relapse rates of 10% are reported in the literature [21]. However, for extended retroperitoneal teratoma the local disease recurrence rates following surgery might be up to 25% [22]. In a recent series of 73 patients with small residual tumors (mean diameter 4 cm) Luz et al. reported an overall complication rate of 27% and found viable tumor in 22% of patients [23]. In 2007, Carver et al. demonstrated that O-PCLND patients with a residual teratoma had a 10-year recurrence-free survival of 80%. The residual tumor size and the IGCCCG risk classification were independent predictors of disease recurrence [24]. These findings are in contrast to our findings: We did not identify surgical technique, IGCCCG risk score, clinical stage or residual tumor diameter as predictors of disease recurrence or OS. This observation could reflect the significant differences of patient characteristics in Carvers cohort compared to our study, especially with respect to the fraction of L-PCLND patients with good prognosis and small residual tumors.

Subramanian et al. published a detailed analysis of 98 O-PCLND patients. Median blood loss was 1000 ml with a consecutive transfusion rate of 42%. Median operating time was 305 min and the median hospital stay 6 days. Overall, intraoperative complication rate was 12%, grade III complications were reported in 6% of cases, 1% each for grade IV and V. Antegrade ejaculation was preserved in 41% of patients. Unfortunately, similarly to other publications no data on tumor diameters were reported which limits comparability to our data [13].

Reviewing O-PCLND series Heidenreich and co-workers concluded that in advanced NSGCTs, a complete resection should be performed for all residual masses irrespective of tumor size, location or histology, thereby providing an excellent long-term disease-free survival of 95% [9]. For smaller tumors, a modified template resection was recommended [11].

Despite the advances in laparoscopic surgery at highly specialized urological centers, L-PCLND still represents an evolving technique. Patient counselling and decision making on surgical technique used largely depends on the surgeon’s experience, tumor characteristics and the patient’s condition.

One of the major drawbacks in obtaining evidence on this important issue is the fact that comparison of the data published in the literature is challenging due to a number of reasons: firstly different eras, in which interventions were performed [25] and secondly different reporting systems of complications. To overcome these issues partly, we incorporated the recently introduced Clavien classification into our study [12]. Unfortunately, most of the previous studies did not use this evidence based classification, thereby precluding a sufficient comparison.

To our knowledge this is the largest study directly comparing L-PCLND with O-PCLND patients. In concordance with previous studies we demonstrated that L-PCLND to represents a safe and reasonable alternative option to O-PCLND for well selected patients with small residual tumors. Both approaches are technically demanding and require a high degree of surgical expertise.

Larger multicenter studies are urgently needed adjust for confounders and better define factors qualifying patients for L-PCLND.

All patients underwent either L-PCLND (n = 46) or O-PCLND (n = 21) at the Charité University Medicine Berlin between October 1999 and March 2010. The Charité department of urology is performing surgery in two different locations. On one campus all residual tumor resections were performed laparoscopically on the other campus all by the open approach. Therefore open and laparoscopic cases were performed concurrently and consecutively.

Data collection was accomplished under an internal review board-approved protocol via retrospective chart review by means of a standardized protocol of the GTCSG. Follow-up was obtained by phone interview with the patients and their local urologists.

Variables of interest were preoperative data on primary histology at the time of orchiectomy, the IGCCCG prognostic risk score at initial chemotherapy as well as tumor marker levels prior to and after chemotherapy [6]. Additionally, patient characteristics and operative details (operative technique, operative time, duration of surgical drainage, intra- and postoperative complications according to Clavien [26], categorized blood loss, concomitant nephrectomy or injury of major vessels) were analyzed.

L-PCLND and O-PCLND technique is described elsewhere [18, 27]. In both surgical approaches a modified template resection was defined by the anatomic boundaries described by Heidenreich and Lattouf et al. [11, 27]. Briefly, the right-sided modified template resection consisted of the precaval, paracaval, retrocaval, and interaortocaval regions as well as the area lateral to the common iliac vessels with the crossing of the ureter as a caudal boundary. The ureter served as the lateral and the renal vein as the cranial boundary. Similarly the left-sided modified template resection included the preaortic area down to the inferior mesenteric artery, the para-aortic and retroaortic regions with the ureteral crossing of the iliac artery as the caudal and the ureter as the lateral boundaries of dissection. A radical template resection was performed in case of contralateral spread, interaortocaval tumor location, or larger residual tumors. For a radical bilateral approach, the dissection fields of the right- and left-modified resections were combined. In defined cases, a nerve-sparing technique as described by Steiner et al. was performed and considered a modified approach [20]. Lumpectomy was defined as a simple resection of the residual tumor.

Blood loss category I was defined as insignificant if <100 ml without transfusion, category II if between 100 ml and 500 ml without transfusion and category III if blood loss was >500 ml with or without the need for intraoperative blood transfusions. The rationale for using surgical drains in the L-PCLND cohort largely depended on the surgeon’s intraoperative assessment of wound secretion.

Differences in categorical variables were analyzed by the Fisher’s exact test, while continuous variables were analysed using the Mann–Whitney U test for non-normally distributed data. Differences in mean estimated OS were calculated by the log-rank test. Predictors of disease-free survival and OS were analyzed in a univariate cox regression model. All tests were two-tailed, differences were considered significant with a p value <0.05. The statistical analysis was conducted with SPSS version 18.0 (SPSS Inc., Chicago, IL, USA).