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1.  Retroperitoneal lymphadenectomy and resection for testicular cancer: an update on best practice 
Therapeutic Advances in Urology  2012;4(4):187-205.
Clinical stage I testicular nonseminomatous germ cell tumours (NSGCTs) are highly curable. Following orchidectomy a risk-adapted approach using active surveillance (AS), nerve-sparing retroperitoneal lymph node dissection (nsRPLND) and primary chemotherapy is recommended by the current guidelines. Clinical stage I is defined as negative or declining tumour markers to their half-life following orchidectomy and negative imaging studies of the chest, abdomen and retroperitoneum. Active surveillance can be performed in low-risk and in high-risk NSGCTs with an anticipated relapse rate of about 15% and 50%. The majority of patients will relapse with good and intermediate prognosis tumours which have to be treated with three to four cycles chemotherapy. About 25–30% of these patients will have to undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for residual masses. Primary chemotherapy with one or two cycles of cisplatin (Platinol), etoposide and bleomycin (PEB) is a therapeutic option for high-risk clinical stage I NSGCT associated with a recurrence rate of only 2–3% and a minimal acute and long-term toxicity rate. nsRPLND, if performed properly, will cure about 85% of all high-risk patients with clinical stage I NSGCT without the need for chemotherapy. PC-RPLND forms an integral part of the multimodality treatment in patients with advanced testicular germ cell tumours (TGCTs). According to current guidelines and recommendations, PC-RPLND in advanced seminomas with residual tumours is only indicated if a positron emission tomography (PET) scan performed 6–8 weeks after chemotherapy is positive. In nonseminomatous TGCT, PC-RPLND is indicated for all residual radiographic lesions with negative or plateauing markers. Loss of antegrade ejaculation represents the most common long-term complication which can be prevented by a nerve-sparing or modified template resection. The relapse rate after PC-RPLND is around 12%, however it increases significantly to about 45% in cases with redo RPLND and late relapses. Patients with increasing markers should undergo salvage chemotherapy. Only select patients with elevated markers who are thought to be chemorefractory might undergo desperation PC-RPLND if all radiographically visible lesions are completely resectable. PC-RPLND requires a complex surgical approach and should be performed in experienced, tertiary referral centres only.
PMCID: PMC3398597  PMID: 22852029
testicular cancer; germ cell tumour; retroperitoneal lymph node dissection; retroperitoneal lymphadenectomy; postchemotherapy RPLND
2.  Predictors of viable germ cell tumor in postchemotherapeutic residual retroperitoneal masses 
Urology Annals  2014;6(1):27-30.
The aim of this study was to identify predictors of viable germ cell tumor (GCT) in postchemotherapeutic residual retroperitoneal masses.
Materials and Methods:
The pertinent clinical and pathologic data of 16 male patients who underwent postchemotherapeutic retroperitoneal lymph node dissection (PC-RPLND) at King Faisal Specialist Hospital and Research Centre between 1994 and 2005 were reviewed retrospectively. It was found that all patients received cisplatin-based chemotherapy for advanced testicular GCT.
Out of the 16 male patients, 2 (13%), 8 (50%), and 6 (37%) had viable GCT, fibrosis, and teratoma, respectively. Ten (10) of the patients with prechemotherapeutic S1 tumor markers did not have viable GCT, and two of the six patients who had prechemotherapeutic S2 tumor markers have viable GCT. All tumor marker levels normalized after chemotherapy even in patients with viable GCT. Four patients had vascular invasion without viable GCT. Furthermore, four patients had more than 60% embryonal elements in the original pathology, but only 1 had viable GCT at PC-RPLND. Four of the five patients with immature teratoma had teratoma at PC-RPLND but no viable GCT; however, out of the four patients with mature teratoma, one had viable GCT and two had teratoma at PC-RPLND. Of the two patients with viable GCT, one had 100% embryonal cancer in the original pathology, prechemotherapeutic S2 tumor markers, history of orchiopexy, and no vascular invasion; the other patient had yolk sac tumor with 25% embryonal elements and 40% teratoma in the original pathology, and prechemotherapeutic S2 tumor markers.
None of the clinical or pathological parameters showed a strong correlation with the presence of viable GCT in PC-RPLND. However, patients with ≥S2 may be at higher risk to have viable GCT. Further studies are needed to clarify this.
PMCID: PMC3963339  PMID: 24669118
Chemotherapy; germ cell tumor; predictor; retroperitoneal lymph node dissection
3.  Retroperitoneal lymph node dissection for residual masses after chemotherapy in nonseminomatous germ cell testicular tumor 
Retroperitoneal lymph node dissection has been advocated for the management of post-chemotherapy (PC-RPLND) residual masses of non-seminomatous germ cell tumors of the testis (NSGCT). There remains some debate as to the clinical benefit and associated morbidity. Our objective was to report our experience with PC-RPLND in NSGCT.
We have reviewed the clinical, pathologic and surgical parameters associated with PC-RPLND in a single institution. Between 1994 and 2008, three surgeons operated 73 patients with residual masses after cisplatin-based chemotherapy for a metastatic testicular cancer. Patients needed to have normal postchemotherapy serum tumor markers, no prior surgical attempts to resect retroperitoneal masses and resectable retroperitoneal tumor mass at surgery to be included in this analysis
Mean age was 30.4 years old. Fifty-three percent had mixed germ cell tumors. The mean size of retroperitoneal metastasis was 6.3 and 4.0 cm, before and post-chemotherapy, respectively. In 56% of patients, the surgeon was able to perform a nerve sparing procedure. The overall complication rate was 27.4% and no patient died due to surgical complications. The pathologic review showed presence of fibrosis/necrosis, teratoma and viable tumor (non-teratoma) in 27 (37.0%), 30 (41.1%) and 16 (21.9%) patients, respectively. The subgroups presenting fibrosis and large tumors were more likely to have a surgical complication and had less nerve sparing procedures.
PC-RPLND is a relatively safe procedure. The presence of fibrosis and large residual masses are associated with surgical complications and non-nerve-sparing procedure.
PMCID: PMC2991320  PMID: 21062470
4.  Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study 
Recent studies have demonstrated that pathological analysis of retroperitoneal residual masses of patients with testicular germ cell tumors revealed findings of necrotic debris or fibrosis in up to 50% of patients. We aimed at pursuing a clinical and pathological review of patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in order to identify variables that may help predict necrosis in the retroperitoneum.
We performed a retrospective analysis of all patients who underwent PC-RPLND at the University Hospital of the University of São Paulo and Cancer Institute of Sao Paulo between January 2005 and September 2011. Clinical and pathological data were obtained and consisted basically of: measures of retroperitoneal masses, histology of the orchiectomy specimen, serum tumor marker and retroperitoneal nodal size before and after chemotherapy.
We gathered a total of 32 patients with a mean age of 29.7; pathological analysis in our series demonstrated that 15 (47%) had necrosis in residual retroperitoneal masses, 15 had teratoma (47%) and 2 (6.4%) had viable germ cell tumors (GCT). The mean size of the retroperitoneal mass was 4.94 cm in our sample, without a difference between the groups (P = 0.176). From all studied variables, relative changes in retroperitoneal lymph node size (P = 0.04), the absence of teratoma in the orchiectomy specimen (P = 0.03) and the presence of choriocarcinoma in the testicular analysis after orchiectomy (P = 0.03) were statistically significant predictors of the presence of necrosis. A reduction level of 35% was therefore suggested to be the best cutoff for predicting the absence of tumor in the retroperitoneum with a sensitivity of 73.3% and specificity of 82.4%.
Even though retroperitoneal lymph node dissection remains the gold standard for patients with residual masses, those without teratoma in the primary tumor and a shrinkage of 35% or more in retroperitoneal mass have a considerably smaller chance of having viable GCT or teratoma in the retroperitoneum and a surveillance program could be considered.
PMCID: PMC3502267  PMID: 23021209
Testicular cancer; Retroperitoneal lymph node dissection; Necrosis; Teratoma
5.  Optimal management of testicular cancer: from self-examination to treatment of advanced disease 
Germ-cell cancer is the most common solid tumor in men aged 15 to 35 years and has become the model for curable neoplasm. Over the last 3 decades, the cure rate has increased from 15% to 85%. This improved cure rate has been largely attributed to the introduction of cisplatin-based chemotherapy. In stage I seminoma and nonseminoma, cure rates approach 100% and treatment is governed by patient choice based on the perceived morbidities of each therapy and personal preferences. For seminoma, treatments include surveillance, radiotherapy, and single course carboplatin. For nonseminoma, treatments include surveillance, retroperitoneal lymph node dissection (RPLND), and adjuvant chemotherapy. Low volume (<3 cm) stage II seminoma is typically managed with radiotherapy while higher volume (>3 cm) stage II and stage III disease treated with chemotherapy. Positron emission tomography (PET) imaging can differentiate active cancer versus necrosis for postchemotherapy residual masses. PET-positive masses are managed with either surgery or second-line chemotherapy. Low volume (<5 cm) stage II nonseminoma with normal serum tumor markers may be managed with either RPLND or chemotherapy. Patients with persistently elevated serum tumor markers and larger volume stage II and stage III disease are managed with systemic chemotherapy. As with seminoma, good risk patients are typically treated with 3 courses of bleomycin, etoposide, and cisplatin (BEP) and intermediate and poor risk patients are treated with 4 courses. Residual postchemotherapy masses should be resected due to the uncertainty of the histology with 50% to 60% harboring residual teratoma or active cancer. The majority of patients completing initial therapy who relapse do so within 2 years. A minority of patients (2%–3%) recur after 2 years and this phenomenon is termed late relapse. Excluding chemonaïve patients, late relapse disease is typically managed surgically with 50% being cured of disease. Current therapeutic challenges in testis cancer include the accurate prediction of postchemotherapy histology to avoid surgery in patients harboring fibrosis only, improved therapy in platinum-resistant and platinum-refractory disease, and the understanding of the biology of late relapse.
PMCID: PMC3818885  PMID: 24198622
testicular cancer; self-examination; advanced disease
Cancer  2010;116(22):5243-5250.
Lymph node counts are a measure of quality assurance and are associated with prognosis for numerous malignancies. To date, investigations of lymph node counts in testis cancer are lacking.
Using the Memorial Sloan-Kettering Testis Cancer Database, we identified 255 patients treated with primary retroperitoneal lymph node dissection (RPLND) for nonseminomatous germ cell tumors (NSGCT) between 1999 and 2008. Features associated with node counts, positive nodes, number of positive nodes, and risk of positive contralateral nodes were evaluated with regression models.
Median (IQR) total node count was 38 (27–53) and was 48 (34 – 61) during the most recent 5 years. Features associated with higher node count on multivariate analysis included high volume surgeon (p=0.034), clinical stage (p=0.036), and more recent year of surgery (p<0.001) while pathologist was not significantly associated with node count (p=0.3). Clinical stage (p<0.001) and total node count (p=0.045) were significantly associated with finding positive nodes on multivariate analysis. The probability of finding positive nodes were 23%, 23%, 31%, and 48% if the total node count was <21, 21 – 40, 41 – 60, and >60, respectively. With a median follow-up of 3.0 years all patients were still alive and 16 patients relapsed while no patient relapsed in the paracaval, interaortocaval, paraaortic, or iliac regions.
Our results suggest that >40 lymph nodes removed at RPLND improves the diagnostic efficacy of the operation. These results will be useful for future trials comparing RPLND, especially when assessing the adequacy of lymph node dissection.
PMCID: PMC4174298  PMID: 20665486
Testicular neoplasms; Lymph nodes; Lymph node excision; Neoplasm staging
Urology  2010;77(2):368-372.
Recent observations suggest that surgeon volume is associated with lymph node counts during retroperitoneal lymph node dissection (RPLND). We report our contemporary single-surgeon experience with lymph node counts during primary RPLND for nonseminomatous germ cell tumors (NSGCT).
Using the Memorial Sloan-Kettering Testis Cancer Database, we identified 124 consecutive patients treated with primary RPLND by a single experienced surgeon for NSGCT between 2004 and 2008. Predictors of positive nodes and number of positive nodes were evaluated with logistic and linear regression models adjusting for year of surgery and clinical stage.
Positive lymph nodes were observed in 37 (30%) while 87 (70%) patients were pN0. Mean total node count was 51 (SD= 23) during the 5 year study period. Mean node counts for the paracaval, interaortocaval, and paraaortic regions were 8 (SD= 6), 17 (SD= 9), and 26 (SD= 15), respectively. In a multivariate analysis, higher total node count was significantly associated with finding positive nodes (odds ratio 1.02 for each additional node counted; p=0.037) and finding multiple positive nodes (coefficient 0.04 for each additional node counted; p=0.004). Year of surgery (p<0.001) was associated with higher total node counts, while clinical stage and pathologist were not (p>0.5 for each).
The average total node count for a primary RPLND by an experienced surgeon is approximately 50 nodes with nearly half of the nodes originating in the paraaortic region. These results will be useful when assessing the adequacy of lymph node dissections for testis, renal, and upper tract urothelial malignancies.
PMCID: PMC4012337  PMID: 21109294
Testicular neoplasms; Lymph node excision; Neoplasm staging; Retroperitoneal space; Lymph nodes
8.  A meta-analysis of patient outcomes with subcentimeter disease after chemotherapy for metastatic non-seminomatous germ cell tumor 
Annals of Oncology  2013;25(2):331-338.
Approximately a quarter of men with metastatic non-seminomatous germ cell tumor (NSGCT) have a residual mass, typically in the retroperitoneum, after chemotherapy. The management of small residual masses (≤1 cm) is controversial, with good outcomes seen with either post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) or surveillance. We sought to review our experience of surveillance and synthesize the cumulative findings with the current literature in the form of a meta-analysis.
Patients and methods
We searched PubMed, EMBASE and abstracts from ASCO and AUA to identify relevant, English-language studies for the meta-analysis. The DFCI (Dana Farber Cancer Institute) database was constructed from a database of men undergoing cisplatin-based chemotherapy for metastatic NSGCT. The outcomes of interest were the proportion with necrosis, teratoma or active cancer on histology at PC-RPLND (literature) and the total number of relapses, RP-only relapses and overall survival in men undergoing surveillance (literature and DFCI cohort).
Three of 47 men undergoing post-chemotherapy surveillance at our institution relapsed over a median follow-up of 5.4 years. All three were alive at a median of 4.2 years after relapse. On meta-analysis, the pooled estimates of necrosis, teratoma and active cancer in the 588 men who underwent PC-RPLND were 71, 24 and 4%, respectively. Of the combined 455 men who underwent surveillance, the pooled estimate of the relapse rate was 5%, with an RP-only relapse rate of 3%. Of the 15 men who suffered an RP-only relapse on surveillance, two died of disease.
Surveillance is a reasonable strategy for men with minimal residual RP disease after chemotherapy and avoids an RPLND in ∼97% of men who are cured with chemotherapy alone.
PMCID: PMC4566003  PMID: 24276027
complete remission; retroperitoneal lymph node dissection; testicular cancer
9.  Management of the residual post-chemotherapy retroperitoneal mass in germ cell tumors 
Therapeutic Advances in Urology  2009;1(4):199-207.
The management of the residual mass in the retroperitoneum following induction chemotherapy for metastatic testicular cancer has evolved over the past three decades. A multidisciplinary approach involving cisplatin-based chemotherapy and postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) has increased long-term survival rates above 80%. Advances into the appropriate patient selection and timing of surgery have lowered morbidity while improving oncologic outcomes. However, areas of controversy still exist within the field. Management of the small residual mass, predictors of the histology of the residual mass, the extent of PC-RPLND, the role of PC-RPLND in the setting of elevated serum tumor markers, and the role of positron-emission tomography are all topics of ongoing research and debate. We will discuss these issues and review the current guidelines for the management of the residual postchemotherapy retroperitoneal mass in this review.
PMCID: PMC3126061  PMID: 21789067
testes; neoplasm; residual; seminoma; neoplasm; germ cell; retroperitoneal lymph node dissection; post-chemotherapy
10.  Sequential bilateral testicular tumours presenting with intervals of 20 years and more 
BMC Urology  2013;13:71.
About 3 – 5% of all patients with testicular germ cell tumour (GCT) develop a contralateral cancer, the majority of which arise within 10–15 years. Little is known about the risk of second GCTs after more than two decades. Here we present 3 cases with very late presenting contralateral GCT and provide a summary of similar cases reported previously.
Case presentations
(1) This white Caucasian man underwent right-sided orchiectomy for a nonseminomatous GCT at the age of 22 years. Additional treatment consisted of retroperitoneal lymph node dissection (RPLND) and chemotherapy with 4 cycles of vinblastin / bleomycin. 36 years later, contralateral seminoma clinical stage 1 developed. Cure was achieved by orchiectomy. Histologically, testicular intraepithelial neoplasia (TIN; intratubular germ cell neoplasia) was detected in the tumour-surrounding tissue.
(2) This white Caucasian male had right-sided orchiectomy for nonseminomatous GCT at the age of 29 years. Pathological stage 1 was confirmed by RPLND. 25 years later, he received left sided orchiectomy for seminoma stage 1. Histologically, TIN was found in the tissue adjacent to seminoma. Two brothers had testicular GCT, too, one with bilateral GCT. (3) This 21 year old white Caucasian man underwent left-sided orchiectomy for nonseminomatous GCT. Pathological stage 1 was confirmed by RPLND. 21 years later, he received organ-preserving excision of a right-sided seminoma, followed by BEP chemotherapy for stage 3 disease. Histologically, TIN was found in the surrounding testicular tissue.
22 cases of bilateral GCT with intervals of 20 or more years have previously been reported, thereof three with intervals of more than 30 years, the longest interval being 40 years.
Apart from increased risks of cardiovascular diseases and non-testicular malignancies, patients with GCT face the specific probability of a second GCT in the long run. This risk persists life-long and is not eliminated by chemotherapy. Contralateral testicular biopsy can identify patients at risk by revealing precursor cells of GCT though false-negative biopsies may occur sporadically. However, in view of the multi-facetted late hazards of GCT patients, this minor surgical procedure might somewhat simplify the long-time care of these patients.
PMCID: PMC4028980  PMID: 24321309
Testicular germ cell neoplasms; Bilateral tumours; Testicular biopsy; Seminoma; Familial germ cell tumours
11.  Clinical outcomes in patients with stage I non-seminomatous germ cell cancer 
Asian Journal of Andrology  2013;15(4):558-563.
This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer (CSI NSGCT) treated with surveillance, retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months (range: 6–149 months). Thirteen of the 89 patients (14.6%) had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China.
PMCID: PMC3739228  PMID: 23685909
chemotherapy; clinical stage I non-seminomatous germ cell testicular cancer (CSI NSGCT); outcome; retroperitoneal lymph node dissection (RPLND); surveillance; treatment protocols
12.  Preservation of Ejaculation in Patients Undergoing Nerve-Sparing Post-Chemotherapy Retroperitoneal Lymph Node Dissection for Metastatic Testicular Cancer 
Urology  2008;73(2):328-332.
We evaluated clinical parameters associated with recovery of ejaculation following nerve-sparing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for non-seminomatous germ cell tumor.
We queried our institutional database for all patients who underwent nerve-sparing PC-RPLND between 1995 and 2005 using a bilateral template. Nerve-sparing was carried out whenever technically feasible and oncologically prudent. Antegrade ejaculation was defined as any seminal fluid expulsion and was determined by patient report. We evaluated recovery of antegrade ejaculation based on clinical and pathologic parameters and fit a logistic regression model to determine which pre-operative variables are associated with antegrade ejaculation.
A total of 341 patients had PC-RPLND during the study period, 136 (40%) with nerve sparing techniques. Post-operative antegrade ejaculation was reported by 107/136 (79%) of patients with information available. On the multivariable analysis, a right-sided primary testicular tumor (OR 0.4, 95% CI: 0.1, 1.0, p=0.044) and residual masses ≥5 cm (OR 0.1, 95% CI: 0.0, 0.7, p=0.020) were associated with retrograde ejaculation. However, 40/54 (74%) with right-sided primary tumors and 4/9 (44%) with mass ≥5 cm reported antegrade ejaculation. The 5-year relapse free survival was 98% with a median follow up of 39 months (IQR 19, 66).
Nerve-sparing PC-RPLND is associated with excellent functional return of antegrade ejaculation, is feasible in select patients with bulky disease, and has excellent oncologic outcomes.
PMCID: PMC3665266  PMID: 19022490
Testicular Cancer; Chemotherapy; Surgery; Ejaculation; Retroperitoneal Lymph Node Dissection
13.  Retroperitoneal lymph node dissection (RPLND) for malignant phenotype Leydig cell tumours of the testis: a 10-year experience 
SpringerPlus  2015;4:20.
Retroperitoneal lymph node dissection (RPLND) is a prognostic, palliative, and potentially therapeutic procedure for patients with malignant phenotype Leydig cell tumours of the testis. We reviewed the records of patients diagnosed with malignant phenotype Leydig cell tumours of the testis treated by RPLND. Modified template dissection was performed in all cases with extra-template excision of tumour mass in Stage II disease. Routine clinico-radiological follow-up was performed. Six open RPLNDs (1 re-do procedure) were performed on 5 patients diagnosed with Stage I (n = 3) and Stage II (n = 2) malignant phenotype Leydig cell tumour of the testis. Median age = 63 years (range = 55-72). Median peri-operative blood loss = 1500 ml (range = 500-1500 ml). Median operating time = 6 h (range = 4.5-6.5). Two patients with Stage II disease developed post-operative complications of acute kidney injury (n = 1) and pneumonia (n = 1). Median length of stay was 8 days (range = 6-11). RPLND specimens from patients with Stage I were tumour-free, whilst patients with Stage II disease had evidence of metastatic tumour. At latest follow-up (median = 13 months, range = 7-22), no patient with Stage I disease had radiological evidence of recurrence, however the two patients with Stage II disease had died due to tumour recurrence at 13 months and 36 months. RPLND for malignant phenotype Leydig cell testicular tumours appears to be well tolerated. Despite surgery, overall outcomes for Stage II appear to be poor due to the disease phenotype. Larger prospective multi-centre studies are required to determine the definitive criteria for surgery in Stage I disease.
PMCID: PMC4300307  PMID: 25625040
Testicular cancer; Leydig cell tumour; Retroperitoneal lymph node dissection (RPLND)
14.  The Total Number of Retroperitoneal Lymph Nodes Resected Impacts Clinical Outcome Following Chemotherapy for Metastatic Testicular Cancer 
Urology  2010;75(6):1431-1435.
Following the multidisciplinary management of metastatic germ cell tumor, approximately 10 to 15% of patients with the histologic finding of fibrosis or teratoma will suffer disease recurrence. We evaluated the prognostic significance of the total number of lymph nodes obtained at post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND).
Materials and Methods
From 1989 to 2006, a total of 628 patients underwent PC-RPLND and were found to have either fibrosis or teratoma. Following Institutional Review Board approval, complete clinical and pathologic data were obtained from our prospective testis cancer surgical database. A Cox proportional hazards regression model was constructed to evaluate the association of the total number of lymph nodes obtained at PC-RPLND on disease recurrence.
On pathologic evaluation, 248 (57%) patients had fibrosis and 184 (43%) patients had teratoma. The median number of lymph nodes resected was 25 (IQ range 15, 37). On multivariable analysis, increasing post-chemotherapy nodal size and decreasing lymph node counts were significant predictors of disease recurrence (p=0.01, 0.04, respectively). For patients with 10 nodes removed, the predicted 2 year relapse free probability was 90%, compared to 97% when 50 nodes were removed.
Our data suggests that the total number of lymph nodes removed and analyzed is an independent predictor of disease recurrence following PC-RPLND. This has implications both for the urologist to assure completeness of resection and for the pathologist to meticulously assess the pathologic specimens.
PMCID: PMC3654386  PMID: 20299079
testis cancer; surgery; chemotherapy; lymph node count
15.  Role of chemotherapy prior to orchiectomy in metastatic testicular cancer—is testis really a sanctuary site? 
ecancermedicalscience  2014;8:407.
A germ-cell tumour (GCT) of the testis is a chemosensitive tumour with high cure rates even in advanced disease. Radical inguinal orchiectomy is the initial procedure used to diagnose it which helps to risk-stratify these patients. However, in patients with life-threatening metastases, primary chemotherapy was attempted in a few studies, followed by delayed orchiectomy. The aim of this review is to study the histopathological findings of delayed orchiectomy and the retroperitoneal lymph node dissection (RPLND) specimens, to assess difference and concordance in response rates in histological types of GCTs in pathological specimens. Overall, 352 patients received initial chemotherapy followed by orchiectomy, and 235 of them had undergone RPLND. Delayed orchiectomy specimens had viable tumour in 74 (21%) patients, scarring/necrosis in 171 patients (48.5%), and teratoma in 107 (30.3%) patients. RPLND specimens had residual disease in 36 (15.3%) patients, scarring/necrosis in 100 patients (42.5%), and teratoma in 99 patients (42.3%). Patients with seminoma who underwent delayed orchiectomy had complete disappearance of tumour in 81.3% of cases, and in non-seminomatous GCT, it was 43.4%. These results raise the question of the existence of a blood–testis barrier in patients with advanced GCT and argue against the testis as a sanctuary site.
PMCID: PMC3936913  PMID: 24624227
primary chemotherapy; delayed orchiectomy; advanced germ-cell tumours; germ-cell tumours
16.  Postchemotherapy Surgery for Germ Cell Tumors—What Have We Learned in 35 Years? 
The Oncologist  2014;19(5):498-506.
Some patients with advanced testicular cancer will have a residual mass after chemotherapy. This review article focuses on the evaluation and role of surgery in treatment of these complex patients. It underscores the selection of patients, vital role of surgery, and its timing and complexity, as well as the appropriate use of surveillance as opposed to surgical extirpation. The authors’ intent is to update the oncologist regarding the role of surgery after chemotherapy for advanced germ cell tumors.
Postchemotherapy surgery for advanced testicular cancer has evolved over the last couple of decades. Patients with nonseminomatous germ cell tumors and residual retroperitoneal mass ≥1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (RPLND). For seminoma, RPLND is considered in those patients with masses ≥3 cm that are also positron emission tomography positive. Masses that occur outside of the retroperitoneum should be completely resected with the possible exception of bilateral lung masses when resection of the first mass shows necrosis. The role of surgery in patients with extragonadal germ cell tumors is most vital in those with primary mediastinal nonseminomatous germ cell tumors. Importantly, patient selection, surgical planning, and consideration of referral to centers with this expertise are important to optimize success.
PMCID: PMC4012964  PMID: 24718515
Retroperitoneal lymph node dissection; Testicular cancer; Postchemotherapy retroperitoneal lymph node dissection; Seminoma; Nonseminoma; Germ cell tumor
Urology  2011;79(2):361-364.
Lymph node counts are a proposed measure of quality assurance for numerous malignancies. Investigation of patient factors associated with lymph node counts are lacking. We sought to determine if body mass index (BMI) is associated with lymph node counts in patients treated with a primary retroperitoneal lymph node dissection (RPLND).
Using the Memorial Sloan-Kettering Testis Cancer Database, we identified 255 patients treated with a primary RPLND for nonseminomatous germ cell tumors (NSGCT) from 1999–2008. The associations between BMI and node counts were evaluated using linear regression models in univariate and multivariable models adjusting for features reported to predict higher node counts (year of surgery, stage, and surgeon volume).
Median BMI (IQR) was 26.1 (23.4 – 28.7) and median (IQR) total node count was 38 (27–53). Median total node count for patients with a BMI <25, 25–<30, and >30 was 35, 42, and 44 nodes, respectively. In a univariate analysis, higher BMI was significantly associated with higher total node counts (coefficient 0.7 nodes for each 1 unit increase in BMI; p=0.026). Features associated with higher node count on multivariate analysis included high volume surgeon (p=0.047), pathologic stage (p=0.017), more recent year of surgery (p<0.001), and higher BMI (p=0.009).
Our results suggest for the first time that BMI is independently associated with higher lymph node counts during a lymph node dissection. If confirmed by others, these results may be important when using lymph node counts as a surrogate for adequacy of a lymph node dissection.
PMCID: PMC4170790  PMID: 22173172
Testicular neoplasms; Lymph nodes; Lymph node excision; Neoplasm staging; Body mass index
18.  Current Update of Management of Clinical Stage I Non Seminomatous Germ Cell Tumors of Testis 
The management of patients with testicular germ cell tumors (GCT) has evolved significantly over the past 30 years with cure rates approaching nearly 100% for low-stage disease and more than 80% for advanced disease. Controversy surrounds about ideal management of clinical stage I non seminomatous germ cell tumors (CS I NSGCT) of the testis due to multiple treatment options available with more or less equal efficacy. Nerve-sparing retroperitoneal lymph node dissection (RPLND), adjuvant chemotherapy with two cycles of bleomycin, etoposide, and cisplatin , or surveillance have all achieved long-term survival in nearly 100% of patients with clinical stage I NSGCT. Retroperitoneal lymph node dissection is still favoured as the therapy of choice for clinical stage I non-seminomatous germ cell tumors in many centres, but as risk factors for the primary tumor have become better understood, surveillance and risk-adapted therapy, including surveillance for low-risk patients and adjuvant chemotherapy for the high-risk group, is now being considered a therapeutic option. The objective of this study is to review current developments in the management of CS I NSGCT testis with emphasis on risk stratification and treatment recommendations.
PMCID: PMC3392487  PMID: 23730098
Testis cancer; NSGCT stage 1; Surveillance; Chemotherapy; RPLND
19.  Quality of Surveillance for Stage I Testis Cancer in the Community 
Journal of Clinical Oncology  2009;27(26):4327-4332.
Patients with clinical stage I testicular germ cell tumors have been managed with adjuvant radiotherapy, chemotherapy, or retroperitoneal lymph node dissection (RPLND). The use of surveillance-only strategies at referral centers has yielded survival outcomes comparable to those achieved with adjuvant therapy. We evaluated compliance with follow-up protocols developed at referral centers within the community.
We identified patients with stage I testis cancer within a large private insurance claims database and calculated compliance of follow-up test use with guidelines from the National Comprehensive Cancer Network.
Surveillance was widely used in the community. Compliance with surveillance and postadjuvant therapy follow-up testing was poor and degraded with increasing time from diagnosis. Nearly 30% of all surveillance patients received no abdominal imaging, chest imaging, or tumor marker tests within the first year of diagnosis. Patients who elected RPLND were most compliant with recommended follow-up testing within the first year. Recurrence rates were consistent with previously reported literature, despite poor compliance.
Surveillance is a widely accepted strategy in clinical stage I testicular cancer treatment in the community. However, follow-up care recommendations developed at referral centers are not being adhered to in the community. Although recurrence rates are similar to those of reported literature, the clinical impact of noncompliance on recurrence severity and mortality are not known. Further prospective work needs to be done to evaluate this apparent quality of care problem in the community.
PMCID: PMC2744273  PMID: 19652075
20.  Treatment of a Population Based Sample of Men Diagnosed with Testicular Cancer in the United States 
Urologic oncology  2008;27(6):604-610.
Testicular cancer is the most common cancer in men age 25 to 35 years. We examined therapy, compliance with guidelines, and survival in a population based sample of men newly diagnosed with testicular cancer.
Materials and Methods
We analyzed the National Cancer Institute's (NCI) patterns of care data on 702 men diagnosed with testicular cancer in 1999. These studies supplement routine data collection by verifying therapy with the patients' treating physician. Follow-up for vital status was available through December 31, 2004.
The majority of the men with localized seminoma were diagnosed while their cancer was localized and more than 80% of received orchiectomy with radiation. For men with seminoma and nonseminoma (NSGCT) tumors the percent receiving chemotherapy increased markedly as stage increased. More than 90% of men with regional and distant NSGCT received chemotherapy. Less than 25% of men with localized NSGCT received orchiectomy and retroperitoneal lymph node dissection (RPLND), about 40% had surveillance following an orchiectomy alone and the other third received orchiectomy and chemotherapy.
The majority of these patients received therapy consistent with guidelines. While there was no significant difference in the use of RPLND in men with localized NSGCT by geographic region, chemotherapy use varied widely. Over 90% of men with localized or regional disease diagnosed in 1999 were alive at the end of 2004. The excellent survival rates point to the need to monitor for late effects of therapy.
PMCID: PMC2782764  PMID: 18799329
Testicular cancer; treatment; surgery; radiotherapy; guideline adherence
21.  Robot assisted laparoscopic retroperitoneal lymph node dissection in testicular tumor 
Urology Annals  2013;5(4):223-226.
The treatment options in clinical stage I nonseminomatous germ cell tumor (NSGCT) of testis are either surveillance, chemotherapy or retroperitoneal lymph node dissection (RPLND). While open RPLND still serves as the gold standard, laparoscopic and robot assisted laparoscopic approaches are gaining popularity. In this report, we share our experience and technique of robot assisted laparoscopic RPLND in a patient with clinical stage Ib NSGCT of testis.
PMCID: PMC3835975  PMID: 24311897
Retroperitoneal lymph node dissection; robotic; testicular tumor
22.  Malignant transformation of testicular teratoma: A chemoresistant phenotype 
Urologic oncology  2008;26(6):595-599.
To review our experience in the management of malignant transformation of teratoma (MTT).
Materials and methods
Nine patients with MTT were identified from January 1980 to August 2005, with all pathological specimens re-reviewed by a single genitourinary pathologist.
Two patients presented with clinical stage I disease in which malignant transformation occurred within the primary testis tumor (rhabdomyosarcoma in 1 and adenocarcinoma in 1). These patients underwent a primary retroperitoneal lymph node dissection (RPLND). No viable tumor was identified in the specimen, and both patients were alive without disease at 16 months follow-up. Of the remaining 7 patients, the clinical stages were IIA (N = 1), IIB (N = 3), and III (N = 3), and all were treated with chemotherapy followed by RPLND. The MTT histology of these RPLND specimens consisted of adenocarcinoma (N = 3), rhabdomyosarcoma (N = 2), angiosarcoma (N = 1), and astrocytoma (N = 1). Following preoperative chemotherapy, a significant radiologic response (defined as more than a 25% reduction in maximum tumor circumferential diameter) was demonstrated in 1 patient, and normalization of serum tumor markers was demonstrated in 6. At a mean follow-up of 5 years, 3 of these 7 patients were alive with no evidence of disease, 1 had persistent disease, and 3 had died of disease, and their median disease-specific survival duration was 4.6 years.
In our experience, MTT is significantly resistant to current chemotherapeutic regimens, as demonstrated by its poor radiologic response to treatment. Alternative therapeutic strategies targeted to MTT are thus needed.
PMCID: PMC4121060  PMID: 18367105
Malignant transformation; Teratoma; Postchemotherapy Retroperitoneal lymph node dissection; Testis cancer
23.  Hospital Surgical Volume, Utilization, Costs and Outcomes of Retroperitoneal Lymph Node Dissection for Testis Cancer 
Advances in Urology  2012;2012:189823.
Objectives. Retroperitoneal lymph node dissection (RPLND) outcomes for testis cancer originate mostly from single-center series. We characterized population-based utilization, costs, and outcomes and assessed whether higher volume affects outcomes. Methods and Materials. Using the US Nationwide Inpatient Sample from 2001–2008, we identified 993 RPLND and used propensity score methods to assess utilization, costs, and inpatient outcomes based on hospital surgical volume. Results. 51.6% of RPLND were performed at hospitals where there were two or fewer cases per year. RPLND was more commonly performed at large urban teaching hospitals, where men were younger, more likely to be white and earning incomes exceeding the 50th percentile (all P ≤ .05). Higher hospital volumes were associated with fewer complications and more routine home discharges (all P ≤ .047). However, higher volume hospitals had more transfusions (P = .004) and incurred $1,435 more in median costs (P < .001). Limitations include inability to adjust for tumor characteristics and absence of outpatient outcomes. Conclusions. Sociodemographic differences exist between high versus low volume RPLND hospitals. Although higher volume hospitals had more transfusions and higher costs, perhaps due to more complex cases, they experienced fewer complications. However, most RPLND are performed at hospitals where there were two or fewer cases per year.
PMCID: PMC3328891  PMID: 22550481
24.  Long-term follow-up of pulmonary function in patients cured from testicular cancer with combination chemotherapy including bleomycin. 
British Journal of Cancer  1993;68(3):555-558.
A follow-up study of pulmonary function in two groups of patients with testicular cancer was performed 6-12 years after treatment. Both groups, 47 patients in each, had undergone retroperitoneal lymph node dissection (RPLND). Patients with pathological stage (ps) II had also received bleomycin (median 270 mg) and cisplatin (median 540 mg) in three or four courses which included vinblastine or etoposide. Patients in ps I and II were similar with respect to age, general health, observation period, inspired oxygen fraction (FiO2) and maximal arterial oxygen pressure (pO2) at RPLND, but four (8.2%) with psII disease developed densities on chest X-ray during chemotherapy. At the long-term follow-up the groups were similar with respect to physical exercise, smoking pattern, present drug treatment and history of cardiopulmonary disease. In both groups forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and single breath transfer factor for carbon monoxide (TLCO) were within normal limits, and no difference was found between the groups. The combined data for both groups showed that smoking was highly associated with impairment in TLCO (P = 0.005), and smoking frequency was negatively correlated to TLCO (P = 0.002). We conclude that 3-4 courses with bleomycin, cisplatin and etoposide/vinblastine in testicular cancer patients do not lead to long-term impairment of pulmonary function.
PMCID: PMC1968399  PMID: 7688978
25.  Sequential resection of residual abdominal and thoracic masses after chemotherapy for metastatic non-seminomatous germ cell tumours. 
British Journal of Cancer  1994;70(5):960-965.
Thirty-eight patients with advanced non-seminomatous germ cell tumours (NSGCTs) underwent multiple surgical interventions (two in 33 patients, three in four patients, four in one patient) after cisplatin-based chemotherapy. All patients had normal serum tumour markers but persistent radiographic masses. The larger mass was routinely resected first. Fifteen patients (39%) had dissimilar histological findings at sequential surgical procedures, 12 of whom demonstrated less favourable pathological features during the first operation and three at the second. Patients who underwent both retroperitoneal lymph node dissection (RPLND) and lung resection showed less favourable histological features in the retroperitoneum in nine cases and in the lung in three cases. Eight of 16 patients (50%) without mature teratoma in their primary tumours showed complete necrosis/fibrosis at all surgical interventions, whereas all patients whose primary tumour was classified as malignant teratoma intermediate demonstrated mature teratoma at least at one anatomical site. As histology of post-chemotherapy residual masses cannot be extrapolated from one anatomical site to another, patients usually are properly managed by excision of all residual masses. In particular, in patients with necrosis/fibrosis at lung resection omission of RPLND is not advised.
PMCID: PMC2033563  PMID: 7524606

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