Laparoscopic Retroperitoneal Lymph Node Dissection with Therapeutic Intent in Men with Clinical Stage I Nonseminomatous Germ Cell Tumors

Introduction

T esticular cancer is the most common solid organ neoplasm in men aged 15 to 34. ¹ Because of imprecise clinical staging modalities, approximately 25% to 35% of men with clinical stage I, nonseminomatous germ-cell tumors (NSGCTs) will harbor occult metastasis in the retroperitoneum. ² The risk of relapse can be even higher in men with high-risk features, such as lymphovascular invasion or a high percentage of embryonal carcinoma, at the time of orchiectomy. ^{3 –5} Given the significant chance of relapse and rigorous surveillance protocols, many men choose either surgery or chemotherapy as upfront treatment after orchiectomy. Both retroperitoneal lymph node dissection (RPLND) and chemotherapy have proven to be an effective means of controlling the retroperitoneum and lead to high cure rates. ^{6 –9} In addition to its therapeutic role, RPLND offers the added benefit of accurately staging the retroperitoneum, limiting chemotherapy to only those who need it, and eliminating retroperitoneal relapses that may be insensitive to chemotherapy.

The last decade has witnessed an increase in the use of minimally invasive approaches for the management of urologic diseases. Initially popularized as a less morbid alternative to radical nephrectomy, laparoscopic and robot-assisted surgery have permeated all aspects of urologic oncology, including kidney, prostate, bladder, and testicular cancer. ^{10 –13} Nowhere has the merits of minimally invasive surgery been more questioned and controversial than in its role in the management of testicular cancer. Critics of laparoscopic RPLND point to initial reports of the procedure used for staging, without attempts to replicate the open approach. Further clouding the exact role of laparoscopic RPLND in the management of stage I NSGTs is the fact that most patients in published reports received adjuvant chemotherapy for low-volume disease, making it impossible to compare its true oncologic efficacy to that of open RPLND. ^{14 –16}

As laparoscopic surgeons have gained more experience, many have moved away from using laparoscopic RPLND as a staging procedure and toward replicating the open technique. In doing so, patients with stage I NSGCTs can benefit from the decreased morbidity of minimally invasive surgery without compromising the therapeutic intent or oncologic efficacy of the procedure. In doing so, surgeons are now performing extended template and full bilateral laparoscopic RPLND. This move toward replication of the open approach is in part evidenced by the fact that, increasingly, patients with low-volume disease are now being observed, rather than given adjuvant chemotherapy. ^13,17,18 The decision to administer chemotherapy in this setting, however, is not automatic after open RPLND and is ultimately dependent on patient and physician preferences.

At our center, over the past 3 years, laparoscopic RPLND has been offered to patients with clinical stage I NSGTs with the intent to replicate the open procedure. The purpose of this study is to report the perioperative outcomes and early oncologic efficacy of laparoscopic RPLND with therapeutic intent for patients with clinical stage I NSGTs.

Patients and Methods

With Institutional Review Board approval, we reviewed the clinical and pathologic outcomes of 26 patients with clinical stage I NSGTs who underwent laparoscopic RPLND with therapeutic intent from July 2006 to March 2009. All procedures were performed by one of two surgeons (MEA or MLG). All patient outcomes were recorded in an institutional approved database.

Both clinical and pathologic staging were assigned according to the American Joint Committee on Cancer staging system. If the radical orchiectomy was performed by a referring urologist, the pathology was reviewed by an expert genitourinary pathologist at our institution. Clinical staging for all patients included preorchiectomy and postorchiectomy serum markers (beta-human chorionic gonadotropin, α-fetoprotein, and lactic dehydrogenase) and a CT scan of the chest, abdomen, and pelvis. All patients included in this cohort were found to have clinical stage I disease (negative postorchiectomy markers and preoperative cross-sectional imaging).

All procedures were performed with the patient supine, with four evenly spaced midline 10-mm trocars. We prefer this configuration because it is the most amenable setup to perform extended and bilateral dissections. Extended template dissections included the following areas:

If macroscopically enlarged lymph nodes were detected intraoperatively, the dissection was extended to the contralateral ureter and included dissection posterior to the contralateral great vessel to complete a full bilateral dissection.

Patients were followed postoperatively every three months for the first 2 years with a history and physical examination, evaluation of serum tumor markers, and chest radiography. A postoperative CT of the abdomen and pelvis was obtained 6 months postoperatively and then yearly thereafter. Patients were asked regarding retrograde ejaculation at every visit. Patients with low-volume (pN₁) disease at the time of laparoscopic RPLND were offered observation as an alternative to adjuvant chemotherapy after discussion with a multidisciplinary team consisting of a urologist and medical oncologist.

Results

The demographics and indications for RPLND are shown in Table 1. The median age of our cohort was 27 (range 18–55 y), and the median follow-up was 22.9 months (range 11–43 mos). A high percentage of embryonal carcinoma (>40%), presence of lymphovascular invasion, or teratoma was present in the primary orchiectomy specimen in 65%, 58%, and 54% of patients, respectively. All patients had primary tumors with at least one of these features. Twelve (46%) of the patients had at least one tumor marker that was elevated preorchiectomy, with all returning to baseline before RPLND.

Perioperative outcomes for the 26 patients who underwent laparoscopic RPLND are shown in Table 2. Eleven (42%), 10 (38%), and 5 (19%) underwent a right, left, or bilateral dissection, respectively. The median operative time was 185 minutes (range 120–345 min), and the median estimated blood loss was 100 mL (range 50–250 mL). No patient needed a blood transfusion intraoperatively or postoperatively. One case was electively converted to an open procedure because of bleeding from a lumbar vein at the renal hilum. Hemostasis was achieved after opening, and the dissection was then completed without further complication. Two patients experienced minor complications (Table 2): One experienced urinary retention and needed Foley catheter reinsertion, and the other complained of abdominal pain and was readmitted for a night of observation without sequelae.

Of the 26 patients, 35% had nodal metastasis at the time of laparoscopic RPLND with 6 and 3 patients having pN₁ and pN₂ disease, respectively (Table 3). The mean number of lymph nodes removed at the time of laparoscopic RPLND was 28 (range 6–82). Of the six patients with pN₁ disease, two (33%) received adjuvant chemotherapy and four (67%) were observed without further treatment. At a mean follow-up of 21.9 months, no patient with pN₁ disease has experienced a recurrence. All four patients with pN₁ disease who did not receive adjuvant chemotherapy are without evidence of disease at a mean follow-up of 24 months. Three patients who had pN₂ disease at the time of laparoscopic RPLND received adjuvant chemotherapy and are without evidence of disease at a mean follow-up of 25 months.

Seventeen (65%) patients were found to have pathologic stage I disease after laparoscopic RPLND. At a mean follow-up of 25.5 months, two (12%) have experienced a recurrence, both of which were not in the retroperitonium. The first patient had a 2.5 cm mediastinal recurrence 8 months after surgery and was treated with three cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy. Because of incomplete resolution, the mass was resected, revealing teratoma. He is currently with no evidence of disease 19 months after mediastinal resection. The second patient presented with a palpable proximal penile mass 6 months after RPLND. Biopsy of the mass was positive for metastatic embryonal carcinoma, and he underwent three cycles of BEP chemotherapy with complete resolution of the mass. He is without evidence of disease 14 months after chemotherapy. One patient (3.8%) reported intermittent retrograde ejaculation, with the remainder of the patients confirming antegrade emission.

Discussion

After radical orchiectomy, patients with clinical stage I NSGTs have several options for further management of their disease, including intensive surveillance, chemotherapy, or RPLND. Regardless of which approach a patient chooses, long-term survival rates are excellent. ² When excellent outcomes are achievable with different therapies, morbidity and quality of life related to such therapies take on even greater importance. The rationale for surgical intervention in patients with clinical stage I NSGTs is driven by the fact that 25% to 35% will be understaged and will harbor occult retroperitoneal metastasis. RPLND effectively treats the retroperitoneum in this group of patients, and can spare many the need for additional chemotherapy and its complications.

While open RPLND remains the standard of care in the United States for patients with high-risk clinical stage I NSGTs, laparoscopic RPLND has gained popularity as a minimally invasive alternative to the open approach. Despite the benefits afforded by a minimally invasive approach, laparoscopic RPLND has been criticized (and often justifiably so) in the literature. Critics point to the fact that nearly all patients who are discovered to have node-positive disease undergoing laparoscopic RPLND in early series received chemotherapy regardless of pathologic stage, making it impossible to delineate the true therapeutic merits of this procedure. Critics have also appropriately cited the lack of retroaortic and retrocaval dissection, inadequate boundaries of dissection, and the use of laparoscopic RPLND as a staging procedure rather than as a therapeutic modality as limitations to this approach. ¹⁹

As laparoscopic skills have advanced, many surgeons have moved toward replication of the open technique. Recently, Nielsen and associates ¹³ reported the multicenter results for 120 patients who underwent a laparoscopic RPLND for clinical stage I NSGCTs. The authors reported a relapse rate of 9% at a mean follow-up of 36 months for patients with pathologic stage I disease, with no recurrence occurring within the boundaries of surgical resection, highlighting the adequacy of retroperitoneal dissection in this cohort. In addition, 10 patients with pathologic N₁ disease were followed without adjuvant chemotherapy, with two patients with recurrence outside of the retroperitoneum who had successful salvage chemotherapy. Steiner et al have also reported their experience with 23 patients with clinical stage I or marker negative stage II disease who underwent a full bilateral laparoscopic RPLND. Of the five patients who were found to be pathologic stage N1, none was treated with chemotherapy and none has had a recurrence at a mean follow-up of 18.6 months.

Our study further supports the adequacy and therapeutic efficacy of a properly performed laparoscopic RPLND with only two (12%) patients who were pathologically stage I experiencing a recurrence, both outside of the retroperitoneum. In addition, four (67%) patients with pathologic N₁ disease after laparoscopic RPLND were observed without chemotherapy and are without recurrence at a mean follow-up of 24 months. Although the overall numbers in our series and others are small, they compare favorably with that of open RPLND series for stage I NSGCTs.

Although open RPLND has been shown to provide excellent control of the retroperitoneum and long-term survival rates, it is not without morbidity. A recent study of open primary RPLND reported a 6% transfusion rate with a mean length of stay of 6 days. ²⁰ Similar to reported laparoscopic series, vascular injury was the most common intraoperative complication (4.5% of cases) while chylous ascites developed in two (1.8%) patients and 14 (12.5%) had an ileus. The antegrade ejaculation rate in this group of patients was 80%, and seven (6.3%) patients needed reoperation for small bowel obstruction in two, incisional hernia repair in four, and ureteral reconstruction in one patient. Interestingly, two patients needed nephrectomy—one for a dysplastic kidney and the other for oncologic reasons.

In another series of open RPLND, Beck and coworkers ²¹ reported more favorable short-term morbidity, noting a mean length of stay (LOS) of 2.8 days and no major complications. In this latter series, however, no oncologic outcomes are presented, and no information regarding nodal yields or antegrade ejaculation is provided.

In our contemporary series of patients, the overall complication rate was low, with no patient experiencing a major complication. In addition, no patient needed a blood transfusion, and the median LOS was 2 days, with 10 (38%) patients discharged on postoperative day 1. Similarly, Poulakis and colleagues ²² found shorter LOS, improved quality of life scores, and a faster return to normal activities in patients undergoing laparoscopic RPLND compared with that of open RPLND. These favorable data may potentially translate into economic advantages both in the form of early hospital discharge and return to work after surgery. Additional advantages are the potential to administer chemotherapy earlier for those who need it and the favorable cosmetic result in a young cohort of men who may be image conscious.

Our study does have several limitations that merit discussion. It is a single-institution, retrospective analysis and therefore is subject to potential bias. The overall follow-up is short, and longer-term follow-up in larger number of patients will be necessary to validate our results; however, most relapses in this patient population occur within the first 2 years after surgery, and therefore our median follow-up of 22.9 months represents reasonable initial follow-up. Despite these limitations, our study adds to the growing body of literature that laparoscopic RPLND can be performed safely and effectively with therapeutic intent for patients with clinical stage I NSGCTs.

Conclusion

Laparoscopic RPLND with therapeutic intent can be performed with acceptable oncologic efficacy and low morbidity. Our data suggest that patients with N₁ disease who have undergone laparoscopic RPLND with therapeutic intent may be safely observed without chemotherapy. Longer follow-up and larger studies are necessary to validate these observations.