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Clinical stage I nonseminoma: surgery versus surveillance.

The presentation of nonseminomatous germ cell tumor confined clinically to the testicle (clinical stage I) is associated with a 30% incidence of occult retroperitoneal metastases. For decades, the standard of care in these patients has been a retroperitoneal lymph node dissection (RPLND), both for staging purposes, and, in the pre-modern chemotherapy era, it was performed with curative intent. The improvements in combination chemotherapy during the past 20 years have resulted in the cure of most individuals with small volume recurrent disease, calling into question the continued need for RPLND. The strategy of surveillance and chemotherapy for the 30% who relapse has gained acceptance, and, with meticulous follow-up, can result in the same excellent cure rates seen in patients treated with the surgical option. Although primary chemotherapy has also been suggested as a treatment option, the majority of patients will receive that chemotherapy unnecessarily, and cure rates with this strategy will not surpass those for surveillance or RPLND. Prognostic factors have been developed that can successfully identify a group of patients who are at an extremely low risk of relapse, thus potentially sparing these individuals any additional therapy. However, attempts to define a very high risk population have been unsuccessful to date, and we await the development of newer biologic markers able to predict which patients are most likely to have occult retroperitoneal disease and therefore most likely to benefit from additional "adjuvant" therapy post-orchiectomy.

Germinoma↗

One-stage approach for retroperitoneal and mediastinal metastatic testicular tumor resection.

BACKGROUND: Eight percent of nonseminomatous germ cell tumors of the testis are associated with postchemotherapy residual masses in both the retroperitoneum and the posterior mediastinum. We describe a transabdominal transdiaphragmatic approach that allows simultaneous resection of these masses. METHODS: After standard retroperitoneal lymph node dissection through a midline laparotomy, an incision parallel to the right crus of the diaphragm was made and extended anteriorly through the muscular portion. Excellent exposure of the lower posterior mediastinum was obtained. Masses located higher than vertebra T8 were resected by extending this incision anteriorly and performing a partial sternal division. A complete median sternotomy can be done to allow subcarinal dissection, as well as pulmonary or anterior mediastinal mass resection. RESULTS: Between 1993 and 1999, 18 patients had simultaneous resection of retroperitoneal and posterior mediastinal masses with this approach. There were no perioperative deaths; 3 patients had minor postoperative complications. After a median follow-up of 3.2 years, the overall 5-year survival rate was 92%, and the 5-year disease-free survival rate was 87%. CONCLUSIONS: The transdiaphragmatic approach to the posterior mediastinum is less aggressive than the thoracoabdominal approach. It is safe and effective for simultaneous resection of postchemotherapy testicular nonseminomatous germ cell tumors located in the retroperitoneum and posterior mediastinum.

Adolescent↗

Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Value of pre- and post-orchiectomy serum tumor marker information in prediction of retroperitoneal lymph node metastases. Swedish-Norwegian Testicular Cancer Project (SWENOTECA).

During a 5-year period (1981-86) 588 consecutive patients with nonseminatous germ cell tumors of the testis were included into a prospective Swedish-Norwegian multicenter study (SWENOTECA) and clinically staged according to the Royal Marsden system. A total of 370 patients (63%) had early clinical stages (CS) of disease; 295 (50%) had CS1, 32 (5%) had CS1Mk+ (CS1 with pathological serum tumor marker patterns after orchiectomy) and 43 (7%) had CS2A disease. Pathological staging with retroperitoneal lymph node dissection (RPLND) of the retroperitoneum was performed in 345 (93%) of the early CS patients and 128 (37%) had pathological stage 2 (PS2) disease; 27% of the CS1, 100% of the CS1Mk+ and 66% of the CS2A patients. The overall clinical staging accuracy was 75%. All the 40 patients with pathological serum AFP and/or HCG patterns before RPLND had PS2 disease, compared to 81/282 (29%) of patients with normal marker patterns. The PS2 patients with pathological marker patterns had significantly more and larger retroperitoneal metastases than those with normal AFP and HCG values. Elevated pre-orchiectomy AFP level indicated significantly reduced risk of PS2 disease in CS1 patients, but this effect became non-significant if the CS1Mk+ and CS2A cases were included into univariate or multivariate analyses. We suggest that the 'good risk' effect of pre-orchiectomy AFP elevation for CS1 cases may be caused by a selection mechanism during the clinical staging process.

Biomarkers, Tumor↗

Paternity in men with stage I testis tumors on surveillance.

PURPOSE: We report long-term paternity in men with stage I testis tumors who were managed initially by surveillance. PATIENTS AND METHODS: One hundred five patients with clinical stage I nonseminomatous germ cell tumors of the testis were entered on a surveillance protocol and followed up for more than 10 years. Actual fertility potential was assessed by pregnancy. RESULTS: Of the 105 patients, 41 (39%) have fathered children, which includes 36 of 78 (46%) patients while on active surveillance and five of 27 (19%) patients after treatment for relapse. Of 63 couples who attempted a pregnancy on surveillance or were presumed capable of impregnation (whether they tried or not), 41 (65%) were successful. CONCLUSION: These results show that the majority of men with stage I testis tumor who are on surveillance after orchiectomy, have a suitable partner, and attempt impregnation achieve a successful pregnancy. Pregnancy rates appear to be less than reported in men who have a nerve-sparing retroperitoneal lymph node dissection (RPLND) because more patients on surveillance require treatment for relapse, which reduces their chances for pregnancy.

Adolescent↗

Distribution of retroperitoneal lymph node metastases in patients with non-seminomatous testicular cancer in clinical stage I.

118 Patients with non-seminomatous testicular cancer (NSTC) in clinical stage I (CSI = no metastases by clinical, radiological and biochemical evaluation) underwent retroperitoneal lymph node dissection (RLND). The operation was done unilaterally (95 patients) in peroperatively tumor-free patients or in those with limited metastatic growth. In 23 patients with more extensive metastases, bilateral RLND was performed. Metastatic lymph nodes were found in 36 patients, and these patients received 3-4 cycles of a cisplatin-based combination chemotherapy. If no metastases were detected the patients had no further treatment. The 5-year disease-free survival rate was 100%. 8 of 82 patients without detected metastases in the operation specimen relapsed (all outside the retroperitoneal space), but were cured by salvage chemotherapy. Solitary metastases were found in 11 patients, whereas 25 patients had more than 1 metastatic lymph node. The size of the largest metastasis ranged from 0.3 to 40 mm. Metastases from right-sided tumors were detected at all levels of the lumbar region, predominantly to the right of the inferior vena cava and/or within the interaortocaval space. Left-sided tumors metastasized to the upper two thirds of the lumbar space, only rarely crossing the midline. This anatomical distribution of metastatic lymph nodes indicates that the presacral sympathetic nerve plexus and the sympathetic nerve fibers around the aortic bifurcation can be spared from extensive resection in the majority of patients with NSTC in CSI. Unilateral RLND or other nerve-sparing techniques are thus possible, preserving antegrade ejaculation in greater than 80% of the patients. This RLND represents a reasonable alternative to the 'surveillance' policy in NSTC.

Adult↗

[A case of extragonadal germ cell tumor with inferior vena caval tumor thrombus].

We report a case of retroperitoneal extragonadal germ cell tumor with tumor thrombus in the inferior vena cava. The patient referred to our hospital with lumbago. Computed tomography (CT) showed a bulky mass in the retroperitoneum. The levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-HCG) in the serum were elevated. Histological examinations indicated embryonal cell carcinoma. Bilateral testicles did not contain any palpable mass upon careful palpation. No tumor mass was detected in the bilateral testicles on ultrasonography. Clinically, the diagnosis was a retroperitoneal extragonadal germ cell tumor associated with para-aortic lymph-node involvement. After the combination chemotherapy (BEP 1 course and EP 3 courses), the tumor mass was reduced in size and the tumor marker was normalized. Retroperitoneal lymph node dissection (RPLND) was performed and tumor thrombus in the inferior vena cava was resected. There was no involvement of the viable cells in the resected tumor. The patient has been in good condition with no evidence of disease.

Adult↗

Excision of residual masses of metastatic germ cell tumours after chemotherapy: the role of extraperitoneal surgical approaches.

OBJECTIVE: To evaluate the efficacy and safety of extraperitoneal surgical approaches for the removal of residual masses of metastatic germ cell tumours in men after chemotherapy. PATIENTS AND METHODS: A series of 75 men (median age 32 years) with metastatic germ cell tumours of testicular (n = 63) or extragonadal (n = 12) origin, who had been treated with an intensive course of platinum-based chemotherapy, were found to have residual tumour masses. Extraperitoneal surgical approaches were used on 80 occasions to excise these masses. A thoraco-abdominal extraperitoneal approach (n = 71) was used for large masses and those with intrathoracic metastases while smaller retroperitoneal masses were removed through 12th rib (n = 5) or Rutherford-Morrison (n = 4) extraperitoneal approaches. RESULTS: Complete macroscopic clearance of residual masses within the thorax and retroperitoneum was achieved in all cases. The median blood loss was 0.8 L and the median in-patient stay was 7 days. Complications included chest infection in four cases. Two patients died about 4 weeks after surgery, one from septic pericarditis and another after an epileptic fit secondary to brain metastases. Eleven patients have developed tumour recurrence, five of whom have died from disseminated disease. Hence the survival rate and disease-free survival rate are 91% and 83%, respectively, with a median follow-up of 22 months. CONCLUSIONS: The thoraco-abdominal extraperitoneal surgical approach for retroperitoneal lymph node dissection after chemotherapy for testicular cancer is safe and has some advantages over anterior approaches, allowing synchronous removal of intrathoracic disease, improved access to nodes above and behind the renal vessels and more rapid post-operative recovery.

Adolescent↗

Management of patients with low-stage nonseminomatous germ cell testicular cancer.

Management options for patients with clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT) include surveillance, retroperitoneal lymph node dissection (RPLND), or two cycles of bleomycin-etoposide-cisplatin (BEP x 2) chemotherapy. The optimal management of these patients is controversial, as cure rates of 97% or greater are reported with each of these treatment modalities. Patients without evidence of lymphovascular invasion, a predominant component of embryonal carcinoma, or advanced pathologic (p) T stage (pT 2 or greater) are at low risk for occult metastases and are optimal candidates for surveillance. Compliance with diagnostic testing and imaging is essential for a successful surveillance strategy to detect and treat metastases at an early stage. For patients who are not candidates for surveillance, RPLND offers several advantages over chemotherapy. RPLND alone is curative in 50% to 80% of CS I patients with pathologic stage (PS) II, and an estimated 75% of CS I patients avoid chemotherapy (as adjuvant therapy or for treatment of relapse). Virtually all patients are cured following two cycles of adjuvant chemotherapy for PS II disease, which is reserved for patients with high-volume (PN2-3) retroperitoneal disease. The poor outcome of patients with late retroperitoneal recurrence from unresected, chemorefractory germ cell testicular cancer indicates that RPLND is a vital component to the long-term cure of patients with NSGCT. Approximately 20% to 30% of patients with PS II disease have retroperitoneal teratoma (which is chemoresistant), and an estimated 5% of PS II patients have chemoresistant viable cancer following BEP x 2 as primary therapy. When RPLND is omitted, these patients are at risk for late recurrence with potentially lethal consequences. Patients who relapse after RPLND are "chemotherapy-naïve" and cured in virtually all cases with good-risk chemotherapy regimens. When nerve-sparing techniques are employed to preserve ejaculation, RPLND is also associated with a more favorable long-term toxicity profile compared with chemotherapy. In the absence of conclusive evidence from a randomized trial, we believe RPLND is the treatment of choice for patients with CS I NSGCT who are not candidates for surveillance, as it offers the greatest likelihood of long-term cure with considerably less morbidity than primary chemotherapy.

Humans↗

[Extragonadal germ cell tumor coexisted with renal cell carcinoma--a case report].

A patient was 31-year-old man with the chief complaint of 38 degrees C fever. He was pointed out left renal tumor by abdominal ultrasonography and computerized tomography (CT). CT revealed left infraclavicular, mediastinal and retroperitoneal lymph nodes swelling and left renal tumor. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG-beta) level were elevated. The diagnosis of extragonadal germ cell tumor and left renal cell carcinoma was confirmed pathologically by infraclavicular lymph node and renal biopsy. He was treated with 4 courses of BEP regimen and interferon-alpha, cimetidine therapy for 2 weeks preoperatively. After serum tumor markers were normal level, he underwent left radical nephrectomy and left infraclavicular, mediastinal and retroperitoneal lymph node dissection. The histology of all lymph nodes was necrotic tissue, but operation was incomplete. Therefore VIP therapy was performed postoperatively. This is the first case of extragonadal germ cell tumor coexisted with renal cell carcinoma in the world.

Adult↗

Staging and surgery in testicular cancer.

Both staging and surgery in testicular cancer are thoroughly analysed. Extensive experiences from various authors are reported and compared. The essentials for staging are suggested and a new detailed stage grouping is proposed. The role of surgery in diagnosis, staging and therapy is examined. It is stressed that in non-seminomas, retroperitoneal lymph node dissection is not only a staging procedure, but it may be also a curative operation in several cases of patients with lymph node metastases and a prospective randomized clinical trial is advocated in order to clarify the usefulness of adjunctive chemotherapy in these cases. Surgery is also useful as adjuvant to chemotherapy in several patients with advanced non-seminomas and it is underlined that it should be undertaken early, after only 2 or 3 cycles of chemotherapy, in order to avoid the strong fibrosis that often occurs after long-term chemotherapy and which makes surgical dissection very difficult or even impossible. Lastly, even if extensive, surgery seems to be a safe procedure in these young patients.

Antineoplastic Agents↗

The management of paratesticular rhabdomyosarcoma: a single institutional experience with 44 consecutive children.

PURPOSE: We report a single institutional experience with 44 consecutive children treated from 1976 to 1996 for paratesticular rhabdomyosarcoma. MATERIALS AND METHODS: After primary surgical excision, 27 cases were classified as Intergroup Rhabdomyosarcoma Study (IRS) group I, 1 as group II, 8 as group III and 8 as group IV. Except for the first 5 patients, retroperitoneal node dissection was not a required staging procedure and was performed only for radiologically suspicious node metastases. Adjuvant chemotherapy was administered to all patients. Additional radiotherapy was given when nodal involvement or residual disease was documented. RESULTS: The 5-year event-free survival rate was 77% for the entire series of patients, 93% for those in groups I and II, 62.5% in group III and 37.5% in group IV with a median followup of 11 years (range 2 to 20). CONCLUSIONS: Our report confirms the excellent prognosis of localized paratesticular rhabdomyosarcoma. Due to the accuracy of computerized tomography potential morbidity of lymphadenectomy, low rate of retroperitoneal recurrence and presumed efficacy of chemotherapy for controlling microscopic disease, retroperitoneal lymph node dissection seems unnecessary for localized disease.

Adolescent↗

Stage I nonseminomatous germ cell testicular tumor: prediction of metastatic potential by primary histopathology.

A study of 60 patients with clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) was conducted to identify prognostic factors that may predict the likelihood of metastasis. Clinical features and histopathologic features of the primary testicular tumor were examined and analyzed for correlations with the presence of retroperitoneal nodal metastasis documented by surgery (N+) and with development of relapse (R+). Pathologic tumor stage greater than or equal to 2, with tumor extension into the tunica albuginea, rete testis, epididymis, or spermatic cord, was correlated with an increased rate of N+ compared with pathologic tumor stage I (P = .001). Vascular invasion was correlated with a higher rate of N+ (P = .05) and had a similar association with R+ (P = .08). Tumors containing less than 50% teratoma were found to have a higher rate of N+ than tumors with greater than or equal to 50% teratoma (P = .02). Based on the identified prognostic factors, a model for predicting the probability of retroperitoneal nodal metastasis in clinical stage I patients is proposed. The risk factors for nodal metastasis are: pathologic tumor stage greater than or equal to 2, vascular invasion, and less than 50% teratoma. Patients with none of the risk factors are considered at low risk and may be offered orchiectomy alone with surveillance for initial treatment. Patients with all three risk factors are at high risk and should be treated with a retroperitoneal lymph node dissection (RPLND) or possibly chemotherapy. Patients with one or two risk factors are at intermediate risk; it is recommended that they undergo RPLND. This risk model facilitates a rational approach to the management of clinical stage I NSGCT.

Adult↗

Prognostic factors in patients with pathological stage I non-seminomatous testicular germ cell tumors and tumor recurrence during follow-up.

Clinical staging in patients with stage I non-seminomatous germ cell tumors (NSGCTs) of the testis fails in 30% to correctly assess pathological stage since microscopic and small-volume retroperitoneal disease is not detectable on computed tomography of the abdomen. Patients staged by retroperitoneal lymph node dissection as pathological stage I incur a distant (chest or serological) tumor relapse rate of 7-15% during follow-up. Recently, we reported on new risk factors as predictors of pathological stage by flow cytometric DNA analysis in clinical stage I patients. These same methods were applied to a group of 14 pathological stage I patients who subsequently had either chest or serological recurrence. The findings in this group of patients were compared with those in a group of 47 pathological stage I patients who did not experience recurrence. In pathological stage I NSGCT patients with distant (chest or serological) tumor relapse, we found by histological evaluation and DNA analysis of the original orchiectomy specimen proliferative tumor activity to be significantly predictive of relapse. Much as proliferative activity of the primary tumor is predictive of retroperitoneal metastasis, it may be a predictor of recurrence in pathological stage I patients.

DNA, Neoplasm↗

Can retroperitoneal lymphadenectomy be omitted in some patients after chemotherapy?

The advances in the therapy of high-volume stage II and stage III testicular cancer have been largely due to the development and success of cisplatin-based chemotherapy. Though patients with low- to moderate-volume stage II disease historically were curable with radical retroperitoneal lymph node dissection, patients with higher volumes of metastatic disease were not curable with surgery alone. The advent of cisplatin-based chemotherapy in the 1970s has allowed many of these patients with higher-volume metastatic disease to be cured. Though chemotherapy clearly plays the major role in the therapy of these patients, surgery after chemotherapy has been complimentary in the overall chance for cure of these patients.

Antineoplastic Agents↗

[Case of testicular cancer with malignant transformation in the residual retroperitoneal mature teratoma 8 years after the initial chemotherapy].

We here report a case of the gradual maturation of teratoma during 8 years after the initial chemotherapy. A 21-year-old man was diagnosed as having a left testicular tumor with retroperitoneal lymph node metastasis around the left renal artery in 1988 and high inguinal orchiectomy was carried out. Histological examination revealed a mixed germ cell tumor composed of immature teratoma, embryonal carcinoma, and seminoma. He received four courses of PVB chemotherapy for his bulky lymph node metastasis. After normalization of the alpha-fetoprotein level, retroperitoneal lymph node dissection (RPLND) was performed. However, the nodes could not be dissected completely because of severe adhesions to the aorta. Histological examination revealed massive necrosis and immature teratoma. One cause of combination chemotherapy with cisplatin and etoposide was given following the surgery. In 1991, enlargement of the residual lymph nodes around the left renal artery was detected by CT scanning. Since both PVB chemotherapy and the combination of cisplatin with etoposide did not achieve remission, RPLND was performed again. Histological examination revealed a mature teratoma which was far more differentiated than that resected in 1988. In 1996, several enlarged para-aortic lymph nodes were found without the elevation of tumor makers, and en-bloc RPLND was performed. Microscopically, mature teratoma was observed in almost all specimens and, unexpectedly, adenocarcinoma was also observed in enteric elements of the mature teratoma. We concluded that we could not evaluate the malignant biological characteristics of teratoma from its maturation level and residual retroperitoneal teratomas should be as completely resected as possible.

Adult↗

Validation of a prediction model and its predictors for the histology of residual masses in nonseminomatous testicular cancer.

PURPOSE: We validated a prediction model for histology of residual retroperitoneal masses, either benign or tumor, in patients treated with chemotherapy for metastatic nonseminomatous testicular cancer. MATERIALS AND METHODS: We studied 276 patients treated with chemotherapy before retroperitoneal lymph node dissection at Indiana University Medical Center between 1985 and 1999. A previously developed prediction model was modified to provide predictions for the Indiana population based on 5 predictors. For these predictors, including teratomatous elements in the primary tumor, pre-chemotherapy tumor markers (alpha-fetoprotein and human chorionic gonadotropin), size of the residual mass and reduction in mass size, univariate and multivariate odds ratios were determined. The modified model was evaluated by calculating the concordance statistic and studying model reliability. RESULTS: All odds ratios from univariate and multivariate analyses were in the expected directions. The modified model had good discriminative ability (concordance statistic 0.79). However, the predicted probabilities for benign tissue were generally too high due to the low prevalence of benign tissue (76 of 276 cases or 28%). CONCLUSIONS: This study confirms the predictive ability of formerly identified predictors for the histology of residual retroperitoneal masses in testicular cancer. However, the previously developed prognostic model must be adjusted for the local overall ratio of benign versus tumor histology to provide reliable predictions in the Indiana population.

Antineoplastic Agents↗

[Clinico-pathologic evaluation of retroperitoneal lymph node metastasis in ovarian carcinoma].

Retroperitoneal lymph node dissection was performed in 18 cases of ovarian carcinoma. Of 18 patients, 8 (44.4%) patients had lymph node metastasis. It was found that 50.0% of patients with stage III and 100% of patients with stage IV had lymph node metastasis. Serous cystadenocarcinoma and poorly differentiated carcinoma were demonstrated to be the risk factors in lymph node metastasis. Lymph node metastasis was found to be significantly correlated with the volume of ascites, peritoneal cytology, or peritoneal dissemination. Patients without peritoneal dissemination or positive peritoneal cytology had no lymph node metastasis. Patients with bilateral ovarian tumors tended to have a higher incidence of lymph node metastasis than those with a unilateral ovarian tumor. The incidence of para-aortic lymph node metastasis was found to be higher than that of pelvic or inguinal lymph node metastasis. We concluded that in the clinical stage, serous cystadenocarcinoma, poorly differentiated epithelial carcinoma, ascites, peritoneal cytology, peritoneal dissemination and bilateral ovarian tumors were assumed to affect the incidence of retroperitoneal lymph node metastasis of ovarian carcinoma. It was suspected that the lymphatic spread of ovarian carcinoma had two routes: via ascites and peritoneal dissemination.

Ascitic Fluid↗