Study Type – Therapy (prospective cohort)
Level of Evidence 2b
Study Type – Therapy (prospective cohort)
To review differences between primary retroperitoneal lymph node dissection (P-RPLND) and RPLND after chemotherapy (PC-RPLND) in a contemporary series of patients with testicular cancer, to validate the proposed low morbidity.
PATIENTS AND METHODS
Patients who had undergone RPLND at our institution in 2001–2008 were identified and their clinical charts reviewed; in all, 190 were identified and perioperative data obtained.
Of the 190 patients who had RPLND, 98 (52%) and 92 (48%) had P- and PC-RPLND, respectively. Histology of the orchidectomy specimen consisted of embryonal carcinoma in 146 (76%) patients, also including lymphovascular invasion in 83 (44%). The mean (range) operative duration was 206 (110–475) min and the mean blood loss was 294 (50–7000) mL. The median hospital stay was 4 days. Mean blood loss, operative duration and hospital stay were significantly less for the P-RPLND than for PC-RPLND groups (P < 0.05). There were 18 (9%) perioperative complications in all. There were no deaths in either group.
The short-term morbidity of open RPLND is acceptable, and open RPLND is safe and effective at select tertiary centres. When compared with historical data, the present contemporary series shows that the operative duration, blood loss and hospital stay have improved, with few complications. These contemporary data should be considered when comparing laparoscopic with open RPLND.
(open) (primary) (laparoscopic) (post-chemotherapy) retroperitoneal lymph node dissection
nonseminomatous germ cell tumour.
Carcinoma of the testis remains the most common malignancy in men aged 15–35 years; with the development of effective multimodal therapy, the cure rate has improved significantly from ≈60% in the 1970s to 98% in 2000 for most patients. Physician and patient preference often dictate the course of treatment options or surveillance, depending on risk factors and clinical stage. Retroperitoneal lymph node dissection (RPLND) remains an integral component in the treatment and cure of testicular cancer. With the introduction of both the modified-template RPLND and nerve-sparing approaches, the morbidity associated with this procedure is minimal. Emerging treatments have now included single-course chemotherapy and laparoscopic RPLND (L-RPLND) with a reported similar efficacy and decreased morbidity than open RPLND (O-RPLND) [1,2]. In addition to selecting low-risk patients for L-RPLND, these studies refer to historical O-RPLND series, and contemporary data are needed. Beck et al. reported the short-term morbidity in a contemporary series of patients treated with primary RPLND (P-RPLND). We sought to further expand these data in our series of contemporary patients who had P-RPLND and RPLND after chemotherapy (PC-RPLND).
PATIENTS AND METHODS
All patients undergoing RPLND through Brigham and Women’s Hospital and Dana Farber Cancer Center from 2001 to 2008 were candidates for inclusion in this study. All patients were identified and perioperative data were obtained. Follow-up was conducted by chart review. Only complete medical records were used in the study to ensure that all necessary information was available and accurate. Complete medical records were defined as those containing information from a preoperative clinic visit to the last documented follow-up visit. These data were extracted from the Brigham and Women’s Hospital RPLND computerized database and analysed accordingly. This project was approved by the Institutional Review Board at Brigham and Women’s Hospital.
At our institution, all patients are evaluated in a multidisciplinary clinic and are counselled about the options of active surveillance, surgery and/or chemotherapy. All cases were preoperatively staged with tumour markers (α-fetoprotein, hCG and lactate dehydrogenase), CT of the abdomen/pelvis and CT of the chest or a chest X-ray. All orchidectomy and RPLND specimens were reviewed and reports confirmed by pathologists at Brigham and Women’s Hospital.
All patients who had P-RPLND had a modified-template, nerve-sparing procedure; all those having PC-RPLND had a bilateral-template and nerve-sparing procedure when deemed appropriate without compromising oncological efficacy.
Differences in operative data between P-RPLND and PC-RPLND patients based on continuous variables were compared using Student’s t-test; all factors were considered simultaneously. No model selection algorithm was used.
In all, 190 patients who had RPLND at Brigham and Women’s Hospital and Dana Farber Cancer Center between 2001 and 2008 were identified. Of these, 146 (76%) patients had embryonal carcinoma, 83 (44%) had lymphovascular invasion (LVI), and there were no perioperative deaths.
Ninety eight (52%) patients had P-RPLND and 92 (48%) had PC-RPLND, with most receiving three cycles of bleomycin, etoposide and cisplatin. The comparison between these groups is summarized in Table 1.
|No. of patients||98||92|
|Mean age, years||28||31|
|Embryonal carcinoma, %||50.8||43.2|
|CS, n (%)|
|I||61 (62)||23 (25)|
|II||37 (37)||65 (71)|
|Pathological stage, n (%)|
|I||54 (55)||35 (38)|
|II||44 (45)||57 (62)|
|Operative duration, min||188||226||<0.001|
|Estimated blood loss, mL||184||413||0.02|
|Length of stay, days||4.1||4.8||0.04|
|Complications, n (%)||7 (7)||11 (12)|
Operative data were analysed and compared between the P-RPLND and PC-RPLND groups; the former had less blood loss (Table 1, P < 0.02) and less operating room time (P < 0.001) than the PC-RPLND group. The hospital stay was significantly less for P-RPLND than PC-RPLND (P < 0.04). There were seven (7%) perioperative complications in the P-RPLND group (three ileus, two postoperative pain and two chylous ascites/pain) and 11 in the PC-RPLND group (six ileus, two postoperative pain, two chylous ascites/pain and one injury to the aorta). All patients responded to conservative management except the last; the laceration was repaired and the patient received a total of 10 units of blood. His histopathology was negative and he otherwise had an uneventful hospital course. There were no deaths in either group.
RPLND remains an important component of therapy in the management of testis cancer. The safety of the procedure has been well described; furthermore, nerve-sparing techniques have substantially decreased morbidity by allowing preservation of antegrade ejaculation [4–6]. In a continued effort to reduce the morbidity of this procedure, advances in minimally invasive surgical techniques have been applied to the surgical management of testis cancer . In series that examined the perioperative outcomes of L-RPLND, the benefits cited include decreased blood loss, shorter hospitalization, and smaller incisions, that can decrease perioperative pain and the need for narcotic pain medication while providing comparable oncological outcomes [7,8].
A recent review that provided a meta-analysis of some larger series of L-RPLND for CS I nonseminomatous germ cell tumour (NSGCT) published after 2000 concluded that in the >800 cases cited in 34 articles, the mean (range) complication rate was 15.6 (9.4–25.7)% and average operative duration was 204 min . These complication rates and operative times are similar to contemporary O-RPLND series, including ours, which had an overall 9% complication rate and mean operative duration of 206 min, inclusive of both P-RPLND and PC-RPLND. When taken separately, our P-RPLND group had a 7% complication rate and mean operative duration of 188 min.
Although L-RPLND is able to approximate the same templates and ability to remove nodes as O-RPLND, the oncological efficacy of L-RPLND in patients who are found to have positive lymph nodes has not been confirmed. Therefore, O-RPLND remains the standard of care. Our series included 190 patients, with 146 (76%) having embryonal carcinoma and 83 (44%) with LVI. Of these, there were 92 (48%) who had PC-RPLND. In a contemporary analysis of O- vs L-RPLND, Nicolai et al. reported that more patients who had O-RPLND had high-risk features then those who had L-RPLND (65% vs 9%), while having fewer complications (6% vs 17%), respectively. O-RPLND had a significantly shorter operative time (140 vs 210 min, P < 0.001) while L-RPLND had a significantly shorter hospital stay (6 vs 4 days, P < 0.001). The authors concluded that patients with high-risk features should be managed with O-RPLND, but there were too few patients to completely disregard L-RPLND as an alternative.
L-RPLND has become established as an effective alternative therapy for the diagnostic and therapeutic management of CS I NSGCT, but in high-risk and post-chemotherapy patients L-RPLND is less firmly established as an effective treatment with minimal morbidity. In the present cohort, 76% of patients had an embryonal component in their orchidectomy specimen and 44% had LVI. These pathological variables were previously associated with a high risk of retroperitoneal disease. In addition, since 2000 we have used PC-RPLND in 92 patients, almost half of the total. There was a significantly greater operative time, blood loss and length of stay between the groups, but there was no difference in complication rate. To date, experience with L-RPLND after chemotherapy is limited to a few small series and case reports assessing the technical feasibility. One of the largest and most recent series consisted of 26 patients who had L-RPLND for residual retroperitoneal tissue after induction chemotherapy . In that series, three patients (12%) required open conversion and there were nine (35%) complications (eight lymphovascular and one intestinal). In another L-RPLND series after chemotherapy, two of seven patients required open conversion and three of seven had major complications . Finally, a recent case of port-site metastasis after post-chemotherapy L-RPLND was reported, adding a laparoscopic-specific complication . Laparoscopy for testis cancer should be performed at dedicated medical centres with expertise in laparoscopy, especially for high-risk patients.
The fibrosis and desmoplastic reaction associated with the effect of platinum chemotherapy on RPLNs accounts for the difficulty of PC-RPLND. The meticulous dissection required in PC-RPLND, which probably accounts for the increase in operative time and other perioperative variables in the present group, did not translate into significantly more perioperative complications. The high complication and open conversion rates in the few published post-chemotherapy L-RPLND series reflect the difficulty of dissection, which is made even more difficult with laparoscopy. In patients after chemotherapy, the benefits of a minimally invasive approach might not outweigh the risks of an untested operation.
Several studies have supported primary chemotherapy for NSGCT with embryonal carcinoma and LVI [14,15]. Bohlen et al. reported that two cycles of cisplatin, vinblastine and bleomycin, or bleomycin, etoposide and cisplatin, were effective definitive treatment in 97% of men with high-risk CS I NSGCT. Grade 4 toxicities were noted in 8% of patients and one patient was only able to tolerate one cycle of cisplatin, vinblastine and bleomycin due to paralytic ileus, and another had cardiac toxicity from bleomycin, which ended his chemotherapy prematurely. In patients with CS II NSGCT, RPLND cannot be safely omitted after induction chemotherapy, as the incidence of viable retroperitoneal disease in the form of teratoma or viable malignancy is ≈20%. Surgical management with RPLND avoids the more rigorous follow-up regimen with CT used for surveillance in primary chemotherapy, a factor becoming especially important as a risk of secondary malignancy [17–19]. Brenner and Hall  noted that 1.5–2.0% of all cancers in the USA might be attributable to ionizing radiation from CT. Patients have an increased attributable lifetime risk of cancer with even one CT scan of the abdomen. This magnitude of risk is inversely proportional to patient age.
In conclusion, the short-term morbidity of O-RPLND is acceptable and it is safe and effective at selected tertiary centres. When comparing L-RPLND and/or chemotherapy to O-RPLND, contemporary rather than historical data should be considered. In considering surgical management, patients with high-risk features should be managed with an open approach until further laparoscopic studies prove otherwise.
CONFLICT OF INTEREST