Long‐term oncological outcome after post‐chemotherapy retroperitoneal lymph node dissection in men with metastatic nonseminomatous germ cell tumour

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To determine whether conformity to standard recommendations of retroperitoneal lymph node dissection (RPLND) after chemotherapy for testicular and primary retroperitoneal nonseminomatous germ cell tumours (NSGCT) and completeness of surgical excision have an effect on oncological outcome.

PATIENTS AND METHODS

This was a retrospective study of patients with testicular and primary retroperitoneal NSGCT, with initial involvement of RPLNs, treated between June 1992 and December 2002 in one institution. We reviewed the clinical, surgical and histological charts of 151 such patients who had a RPLND after first‐line platinum‐based chemotherapy. The recommendations used to define conformity to RPLND standards were: the indication based on initial and residual lymph node size, shrinkage, extension of dissection and completeness of resection.

RESULTS

RPLND conformed to standard recommendations in 70 of the 151 (46%) patients. Conformity was complete for the surgeon who operated on 48 patients and was 26% of the others. Fifteen patients (10%) relapsed in the retroperitoneum, 14 of whom had initial lymph nodes of ≥5 cm. Two patients (3%) relapsed in the group of 70 patients with conformed and complete RPLND, vs 13 (16%) in the 81 with conformed but incomplete resection or with non‐conformed and complete or incomplete RPLND. After a median (range) follow‐up of 77 (1.3–186.5) months 132 patients were alive with no evidence of disease, 18 died and one was alive with progressive disease. The limitations of this study were the relatively few patients and that it was retrospective.

CONCLUSION

There was conformity of RLNPD to the recommendations, and completeness of resection, in half of the patients operated; this might have an effect on oncological outcome. Our data suggest that patients should be treated in tertiary centres.     

Postchemotherapy retroperitoneal lymph node dissection is effective therapy in selected patients with elevated tumor markers after primary chemotherapy alone

Objectives

Elevated tumor markers after primary chemotherapy for metastatic testis cancer are usually an indication of persistent cancer. Subsequent treatment has usually been salvage chemotherapy. This article examines the possibility that selected patients can achieve long-term disease-free survival with surgery alone.

Methods

Using a computerized data base of 627 postinduction chemotherapy retroperitoneal lymph node dissections (PC-RPLND), 23 patients with elevated tumor markers who have undergone PC-RPLND after induction chemotherapy alone were identified. Of the 23 patients, 15 were considered candidates for salvage chemotherapy, but instead underwent salvage surgery. Case histories were reviewed to establish selection criteria for PC-RPLND.

Results

Eight patients originally presented as clinical Stage C, 6 as clinical Stage B-3, and 1 as clinical Stage B-2. All patients initially received cisplatin combination chemotherapy. Twelve patients had an elevated alpha-fetoprotein level and 3 patients had an elevated beta human chorionic gonadotropin level prior to PC-RPLND. Seven patients had rising markers at the time of PC-RPLND. Seven patients had teratoma only in their resected specimen and all have no evidence of disease [NED) at a median of 35 months. Two patients had necrosis only in their RPLND specimen and both are NED at 10 and 42 months. Six patients had cancer in their resected specimen and 2 are NED, 1 is alive with disease, and 3 are dead of disease. Five of the 6 patients with cancer in their resected specimen were the only patients who received postoperative chemotherapy.

Conclusions

Some patients with modest elevations of tumor markers after induction chemotherapy may only have teratoma or necrosis in the postchemotherapy resected specimen. These patients (n = 9) remain continuously NED. Patients who undergo salvage surgery and have cancer in the resected specimen do less well, but selected patients can be cured with this modality and thus avoid the morbidity of salvage chemotherapy.     

Post‐chemotherapy nerve‐sparing laparoscopic retroperitoneal lymph node dissection in stage IIB testicular cancer

We report our experience of extraperitoneal nerve‐sparing laparoscopic retroperitoneal lymph node dissection after chemotherapy. Six patients were diagnosed with non‐seminomatous germ cell tumor after orchiectomy and clinical stage IIB disease. Nerve‐sparing laparoscopic retroperitoneal lymph node dissection was carried out for residual retroperitoneal tumors after cisplatin‐based chemotherapy. The median tumor diameter was 2.95 cm before chemotherapy and 1.95 cm after chemotherapy. A modified left (n = 1), right (n = 1) and bilateral (n = 4) template for the dissection area was used. Surgery was successfully completed in all patients and no conversion to open surgery was necessary. Median operative time was 394 min (range 212–526 min). Median blood loss was 75 mL (range 10–238 mL). The overall complication rate was 33.3% (2/6). Two patients had prolonged lymphatic leakage (grade I), which was managed conservatively. Antegrade ejaculation was preserved in all six patients. The histopathological findings showed that two patients had mature teratoma and four patients had necrotic tissue. After a median follow up of 30 months (range 24–36), no recurrence of disease was observed. We can conclude that extraperitoneal nerve‐sparing laparoscopic retroperitoneal lymph node dissection for residual tumors after chemotherapy is a feasible operation. The oncological outcomes need to be confirmed in a certain number of patients with longer follow up.     

Extraperitoneal laparoscopic retroperitoneal lymph node dissection in supine position after chemotherapy for advanced testicular carcinoma

AIM: To evaluate the feasibility and usefulness of extraperitoneal laparoscopic retroperitoneal lymph node dissection (RPLND) in the supine position after chemotherapy for advanced testicular carcinoma. METHODS: Three patients with advanced testicular cancer underwent chemotherapy. Although serum markers were decreased compared with the normal range, residual masses requiring surgical resection were recognized by computed tomography scanning. We applied extraperitoneal laparoscopic RPLND. The patients were placed in the supine position and the first trocar was inserted two finger widths medial to the anterior iliac spine. The retroperitoneal space was dilated using a preperitoneal distention balloon. Two more ports were inserted into the retroperitoneal space and surgery proceeded thereafter. RESULTS: The residual tumors were completely resected by laparoscopy. The procedure required 250-310 min and the bleeding volume was below 50 mL. Although the histopathological findings consisted only of necrosis in all of the patients, one patient recurred at the same place. CONCLUSIONS: Extraperitoneal laparoscopic RPLND in the supine position for residual tumors after chemotherapy is technically feasible and useful in terms of postoperative recovery. With regard to cancer control, further evaluation should be necessary.     

Sexual dysfunction in testicular cancer patients subjected to post‐chemotherapy retroperitoneal lymph node dissection: a focus beyond ejaculation disorders

Post‐chemotherapy retroperitoneal lymph node dissection (PC‐RPLND) represents an integral part of multidisciplinary treatment of advanced germ cell cancer; however, it is associated with a high complications rate. The present study aimed to describe sexual disorders in 53 patients with testicular cancer who underwent full bilateral, non‐nerve‐sparing PC‐RPLND in our institution, focusing beyond ejaculatory dysfunction. The International Index for Erectile Function (IIEF) questionnaire was used as diagnostic tool of male sexual functioning pre‐operatively and three months after RPLND, while post‐operatively patients were asked to describe and evaluate changes in selected sexual parameters. Study findings demonstrate mixed pattern of changes in sexual functioning, with no difference in erectile functioning before and after operation. However, orgasmic function and intercourse and overall sexual satisfaction were found significantly impaired post‐operatively. Sexual desire and frequency of attempted sexual intercourses were found significantly increased post‐operatively, in comparison with pre‐operative levels. With regard to patients' subjective perception on sexual functioning alterations after PC‐RPLND, a significant number of patients reported higher levels of sexual desire, no difference in erectile function and worse orgasmic function and satisfaction post‐operatively. Thus, patients subjected to PC‐RPLND should be closely and routinely evaluated due to close relationship of sexual dissatisfaction with secondary psychological disorders.     

Beneficial impact of a clinical care pathway in patients with testicular cancer undergoing retroperitoneal lymph node dissection

PURPOSE: Since 1997, we have used a clinical collaborative care pathway for patients undergoing retroperitoneal lymph node dissection. We examined its impact on perioperative care and outcome. MATERIALS AND METHODS: We examined the records of all patients with germ cell carcinoma who underwent retroperitoneal lymph node dissection from July 1990 to July 2001. Variables examined included clinical/pathological stage, hospital stay, postoperative care and the complication rate. RESULTS: A total of 118 patients underwent retroperitoneal lymph node dissection for germ cell carcinoma during this period, including 46 (39%) before pathway implementation in 1997 and 72 patients (61%) after pathway implementation. Of the 118 patients 40 (34%) underwent the procedure after chemotherapy. This rate remained fairly constant in the period before and after pathway initiation (31% and 36%, respectively). After pathway implementation fewer patients received a nasogastric tube (94% versus 5%, p <0.001) and had complications (26% versus 16%, p = 0.036). Mean hospital stay decreased after pathway implementation in all primary and post-chemotherapy retroperitoneal lymph node dissection cases (4.2 versus 6.4 days, p <0.005). Although patients who underwent the procedure after chemotherapy were more likely to have complications than those who underwent a primary procedure, the difference was not statistically significant (p = 0.09). CONCLUSIONS: Our collaborative clinical care pathway safely and efficiently outlines routine postoperative care and significantly decreased hospital stay.     

Retroperitoneal lymph node dissection after chemotherapy in patients with elevated tumour markers: indications, histopathology and outcome

OBJECTIVE

To evaluate the factors affecting outcome and the pathological findings in patients who had retroperitoneal lymph node dissection (pcRPLND) after chemotherapy with elevated tumour markers, as such patients have an unfavourable prognosis, with further salvage chemotherapy being the usual treatment of choice.

PATIENTS AND METHODS

Information on the preoperative treatment, tumour markers, histopathology and outcome data of the patients who had pcRPLND were extracted from the hospital databases. Survival was analysed using the Kaplan‐Meier method and multivariate analysis with Cox regression model.

RESULTS

In all, 358 patients had pcRPLND between September 1992 and April 2006, by one surgeon. In 48 patients the tumour markers were elevated at the time of surgery, they were on a ‘rising trend’ in 26 (54%) and ‘downward or stable’ trend in 22 (46%). The overall incidence of active germ cell tumour, differentiated teratoma and necrosis in the resected specimens was 58%, 25% and 17%, respectively. The median follow‐up was 51.5 months and the overall 5‐year survival was 69%. The favourable prognostic factors assessed by univariate analysis were elevation of α‐fetoprotein alone, complete resection of residual disease, histological finding of differentiated teratoma in the resected tissues and normalization of tumour markers after pcRPLND. By multivariate analysis the only statistically significant independent survival factor was the normalization of the tumour markers after pcRPLND.

CONCLUSION

For selected patients with elevated tumour markers after chemotherapy, RPLND can offer a significant chance of cure with no need for further chemotherapy. The patients most likely to benefit are those with elevations of α‐fetoprotein alone. In this group, pcRPLND can offer the prospect of long‐term survival and should be considered in the management of selected patients.     

Gasoline exhaust damages spermatogenesis through downregulating α6‐integrin and β1‐integrin in the rat model

The health influence of air pollution has been an international public health concern. Increasing evidence has suggested that air pollution has been associated with decreased sperm quality. However, the underlying molecular mechanisms are still not fully elucidated. We aimed to verify whether gasoline exhaust leads to reproductive impairment by injuring spermatogonial stem cells and explore its underlying molecular mechanism. Twenty male Sprague‐Dawley rats were randomly divided into two groups: the exposure group (n = 10) and the control group (n = 10). After 6‐month exposure, the sperm count and morphology were determined. The histological changes in the seminiferous tubules were examined by HE staining. The expression of α6‐integrin and β1 ‐ integrin was assessed with Quantitative RT‐PCR, Western blot and Immunohistochemical staining. Compared with control group, male rats exposed to gasoline exhaust showed significantly reduced sperm count, increased sperm abnormality rate and the total number of spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids were decreased. (all p < .01). The expression levels of α6‐integrin and β1 ‐ integrin in the exposure group were significantly lower than those in the control group (all p < .01). Our study showed that exposure to gasoline exhaust caused impairment to spermatogonial stem cells through downregulating α6‐integrin and β1 ‐ integrin.     

A simple model for predicting nodal metastasis in patients with clinical stage I nonseminomatous germ cell testicular tumors undergoing retroperitoneal lymph node dissection only

PURPOSE: In patients with clinical stage I nonseminomatous germ cell testicular tumor the identification of risk categories for nodal metastases and/or distant metastases could permit selective management. We built 2 models for distinguishing these risk categories. MATERIALS AND METHODS: Data on 322 consecutive patients with clinical stage I nonseminomatous germ cell testicular tumor patients treated with retroperitoneal lymphadenectomy (RPLND) alone between 1985 and 1995 were analyzed. The interval between orchiectomy and RPLND, vascular invasion (VI), pT stage, percent embryonal carcinoma (ECa) and teratoma in the primary tumor were considered clinically relevant for their association with nodal or distant metastases. Two logistic models were constructed. Model 1 was meant to discriminate 2 patient categories, namely those with and without nodal metastases at RPLND. Model 2 was meant to discriminate 3 patient categories, namely those without any metastases, with nodal metastases only and with distant metastases independent of retroperitoneal metastases. The models were based on these above variables, which were inserted as categorical and then processed through a backward selection procedure. RESULTS: At RPLND nodal metastases were found in 60 patients (18.6%). During followup distant metastases were observed in 43 patients (13.4%) and retroperitoneal recurrences were noted in 6 (1.9%). Of all recurrences 93.8% were within 2 years since RPLND. RPLND had a high curative rate since 73% of all pN+ cases were cured by surgery alone. The final logistic model 1, including percent ECa and VI, was reassessed in 202 patients with available data. Absent VI and ECa 90% or greater identified a category of 110 patients at low risk for nodal metastasis (14%), while VI and/or ECa greater than 90% identified a category of 92 at higher risk (35%). The identified categories were also related to distant metastases, which occurred in 9.3% of low risk and in 23.1% of high risk cases. Model 2 was not clinically suitable because it did not allow us to distinguish patients at risk for nodal metastases only from those at risk for distant metastases. CONCLUSIONS: Simplicity is the main advantage of model 1 since only 2 well-known prognostic parameters are involved. Although the model must be validated in an independent case series, the identification of a low risk category with few expected nodal metastases could permit us to replace traditional RPLND with a less invasive staging procedure.     

Outcomes in patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection

OBJECTIVES: To evaluate the rates of local and systemic progression (LP and SP), recurrence-free survival and overall survival for patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection (PLND) in 1987-2000. PATIENTS AND METHODS: A consecutive series was analysed of 385 patients (median age 61.9 years, range 30.7-83.8) treated by limited bilateral PLND and radical cystectomy (RC) between 1987 and 2000, with negative surgical margins on final pathology. All patients were staged N0M0 before RC, and none received neoadjuvant radiotherapy or chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and bifurcation of iliac vessels to the circumflex iliac vein. LP was defined as a radiographic soft-tissue density of > or = 2 cm below the bifurcation of the aorta. Pathological characteristics, based on the 1997 Tumour-Nodes-Metastasis system, recurrence patterns, and recurrence-free and overall survival, were determined. RESULTS The median (range) overall follow-up was 45.1 (1.1-165.6) months; the number of lymph nodes (LNs) reported per patient was 12 (2-32). Of the 385 patients, 130 (33.8%) had evidence of LP and 60 (15.6%) of SP. The 5-year recurrence-free and overall survival rates were both 71% for patients with organ-confined, N0 tumours, and 23% and 26% for unconfined, N0 tumours. Positive LNs were found in 45 (12%) patients, who had a recurrence-free and overall survival rate of 9% at 5 years. CONCLUSION: Compared with published reports of similar cohorts of patients managed with RC and extended PLND, the present study suggests that limited PLND is associated with suboptimal staging, greater rates of LP, and lower rates of recurrence-free survival, particularly for patients with unconfined or LN-positive disease.     

Adhesion molecules α, β and γ‐catenin as prognostic factors of tumour progression in upper urinary tract urothelial tumours: the role of AKT‐P/GSK‐3β/β‐catenin pathway

OBJECTIVES

To evaluate α, β and γ‐catenin expression in upper urinary tract urothelial tumours (UUTC) and determine their value as prognostic factors; to investigate the correlation between the catenin complex and the AKT pathway.

PATIENTS AND METHODS

We retrospectively analysed 114 consecutive patients treated at our institution from 1990 to 2004; the mean follow‐up was 54 months. Tumour samples were available from 70 patients, and included in tissue microarrays for immunohistochemical analysis. The antibodies used were anti‐α, ‐β and γ‐catenin, and antiphospho‐AKT. The prognostic value of the expression of these molecules was analysed using tumour progression and cancer‐specific survival as end‐points.

RESULTS

Of the 114 patients, 27% developed tumour progression; the cancer‐specific and overall survival were 77% and 60.6%, respectively. Abnormal α, β and γ‐catenin expression was found in 44 (63%), 22 (31%) and 28 (41%) patients, respectively; the abnormal catenin expression patterns correlated with each other. Positive cytoplasm phospho‐AKT expression was found in 27 (39%) patients. Three of them were found to have cytoplasmic β‐catenin accumulation and none of them nuclear expression. β‐catenin expression was the only one that was an independent marker of tumour progression, with a hazard ratio (95% confidence interval) of 3.1(1.2–8.6), together with grade (7.1, 1.2–55.8) and stage (4.6, 2.1–10). In the cancer‐specific survival analysis, again β‐catenin was an independent prognostic factor (3.4, 1–11.5) together with stage (4.6, 2.2–9.8).

CONCLUSIONS

The loss of the normal membrane β‐catenin expression constitutes an independent factor of tumour progression and cancer‐specific survival. Our data suggest that the AKT/GSK3β/β‐catenin signalling pathway is not activated in the UUTC carcinogenesis.     

Laparoscopic retroperitoneal lymph node dissection combined with adjuvant chemotherapy for pathological stage II disease in nonseminomatous germ cell tumours: a 15-year experience

OBJECTIVE

To present our 15‐year experience of laparoscopic retroperitoneal lymph node dissection (LRPLND) combined with adjuvant chemotherapy (after RPLND) for patients with nonseminomatous germ cell tumour and positive nodes (pN+), evaluating the morbidity and long‐term oncological outcome.

PATIENTS AND METHODS

Data for 87 patients with clinical stage I GCT were collected prospectively from 1992 to 2007. Primary diagnostic LRPLND was performed for pathological staging using a modified‐template dissection. Patients with lymph node involvement had adjuvant chemotherapy, with two cycles of bleomycin, etoposide and cisplatin.

RESULTS

The mean (range) operative duration was 177 (68–360) min, and the hospital stay 6 (4–18) days. Positive nodes were identified in 24% of patients, who subsequently had adjuvant chemotherapy. After a mean (range) follow‐up of 84 (1–186) months, distant relapse occurred in 9% of patients with pathological stage I (no adjuvant chemotherapy), including three patients with pulmonary metastases, two with retroperitoneal recurrence (outside the template field), two biochemical recurrences (α‐fetoprotein elevated) and one port‐site metastasis. No patients with pN+ disease relapsed. There were complications after surgery in 9% of patients, i.e. one pulmonary embolus, one lymphocoele, temporary ureteric stenting in two, ureteric stenosis requiring surgical repair in three and retrograde ejaculation in one patient. All patients remain disease‐free.

CONCLUSIONS

After gaining experience, LRPLND has comparable operative times to contemporary open series, and low morbidity. The two retroperitoneal recurrences (2.5%) were outside the template field. No patients with pN+ had a recurrence, showing the efficacy of adjuvant chemotherapy. Our approach provides excellent oncological outcomes, avoiding intensive surveillance.