Surgical salvage therapy for malignant intrathoracic metastases from nonseminomatous germ cell cancer of testicular origin: analysis of a single-institution experience

BACKGROUND: Cisplatin-based chemotherapy followed by surgical extirpation of residual benign disease represents the usual sequence of curative therapy for metastatic nonseminomatous germ cell cancer of testicular origin. Occasionally, residual disease is malignant in the form of either a persistent nonseminomatous germ cell cancer tumor or degeneration into non-germ cell cancer. We reviewed our institution's experience with patients undergoing salvage operations to remove malignant intrathoracic metastases. METHODS: From 1981 through 2001, 438 patients with nonseminomatous germ cell cancer had operations to remove residual intrathoracic disease after cisplatin-based chemotherapy at Indiana University Hospital. A subset of 134 patients who underwent 186 surgical procedures to remove malignant metastases is the basis of this review. Fifty-nine patients had removal of pulmonary metastases, 49 had removal of mediastinal metastases, and 26 had removal of both pulmonary and mediastinal metastases. Surgical pathology demonstrated 84 patients with persistent nonseminomatous germ cell cancer tumors, 38 with degeneration into non-germ cell cancer, and 12 with both malignant pathologic categories. RESULTS: There were 4 (3.7%) operative deaths. The overall median survival was 5.6 years, with 55 (42.3%) patients alive and well after a mean follow-up of 5.1 years. Seventeen variables were analyzed by using Cox regression. Of these, older age, pulmonary metastases (vs mediastinal metastases), and 4 or more (vs 1) total intrathoracic metastases were significantly (P < or = .01) predictive of inferior long-term survival. CONCLUSIONS: Salvage thoracic surgery to remove malignant metastases from nonseminomatous germ cell cancer tumors of testicular origin can result in long-term survival in select patients. We identified variables that influence survival in this subset.     

Improved prognosis of patients with intermediate- and poor-risk nonseminomatous germ cell tumours by optimizing combined treatment

OBJECTIVE: To assess whether the optimal use of combined treatment with chemotherapy and appropriately timed surgical intervention by a specialized team might improve the outcome for patients with poor- and intermediate-prognosis (International Germ Cell Consensus Classification, IGCCC) nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: Between 1984 and 1998, 47 patients with intermediate (16) and poor prognosis (31) NSGCT were treated; 43 had a testicular and four a retroperitoneal primary. RESULTS: Of the 47 patients only seven (15%) had a complete radiological response after primary chemotherapy; 36 (77%) required surgery after chemotherapy (29 para-aortic lymphadenectomy, 13 resection of pulmonary metastases, two each excision of supraclavicular and retrocrural lymph nodes and one resection of brain metastases; 13 required surgery at more than one site). There was no surgical mortality, with postoperative wound pain the commonest morbidity. On pathology, the resected masses were mature teratoma in 13, necrosis in 12 and malignant disease in 11 patients, the resection being complete in 30. There were microscopically positive margins in the other six patients, all but one having viable residual cancer. Of the 47 patients, 18 needed treatment for relapse, with four having surgery for growing mature teratoma, six chemotherapy plus surgery and eight salvage chemotherapy alone. Of 31 patients, 22 (71%) with a poor and 13 of 16 with an intermediate prognosis were alive at a median (range) follow-up of 94 (41-171) months; of all 47, 34 (72%) remain in complete remission. Ten patients died from disease progression. The presence of residual malignant disease at the resection margin was significantly associated with poorer survival (hazard ratio 7.21, P = 0.0016). Prognostic factors, e.g. number of involved sites, IGCCC group and viable tumour in resected masses, were not significant. The 5-year overall and relapse-free survival (95% confidence interval) was 81 (69-93)% and 57 (43-71)%, respectively. CONCLUSION: The optimal delivery and timing of chemotherapy and surgical resection by a specialist team of oncologists, urological and cardiothoracic surgeons is critical in treating poor-risk NSGCT and might be responsible for improving the outcome of these patients. The detection of residual malignant disease after chemotherapy by positron emission tomography should be investigated to identify those who might benefit from further systemic treatment before complete surgical resection.     

Predictors of residual mass requiring surgical resection after chemotherapy of stage III testicular cancer. A prospective study.

In a prospective study, 63 patients with histopathologically proved Stage III nonseminomatous testicular cancer (NSTC) were analyzed to predict the need for surgical resection of residual masses after cis-platinum-based chemotherapy. Of these 63 patients, 23 (37%) had residual masses after cis-platinum-based chemotherapy requiring surgical resection. Of the 23 patients undergoing surgical resections for their residual masses, 18 patients (78%) had matured teratoma, 3 (13%) had fibrosis with necrosis, and 2 (9%) had residual tumors. Twenty of the 23 (91%) patients with residual disease had either teratomatous elements in primary tumor or bulky metastatic disease at the time of initial chemotherapy. Two patients had incomplete resection of the metastatic disease containing teratoma and required additional resection of recurrent growing matured teratomas. We conclude that teratomatous elements in primary tumor having also bulky metastatic disease are strong predictors of residual disease after initial chemotherapy requiring surgery (21 of 23 or 91%).     

Prediction of necrosis after chemotherapy of advanced germ cell tumors: results of a prospective multicenter trial of the German Testicular Cancer Study Group

PURPOSE: We evaluated the prognostic parameters of necrotic residual tumors after chemotherapy of advanced germ cell tumors to improve on the current indications for surgery. MATERIALS AND METHODS: Between January 1996 and January 2000, in 8 centers of the German Testicular Cancer Study Group, preoperative parameters were assessed to predict necrosis in the residual tumors of 261 patients with retroperitoneal residual tumor resection after first (92%) and second line (8%) chemotherapy. RESULTS: Of 232 evaluable patients 39 had pure seminoma and 5 had viable cancer (1 with seminoma) in the residual tumor. Of the remaining 193 patients with nonseminoma 35% had necrosis, 34% teratoma and 31% had viable carcinoma in the residual tumor. After multivariate analysis and exclusion of patients with seminoma, the 3 parameters independently predictive of necrosis were alpha-fetoprotein before chemotherapy less than 20 ng/ml, and tumor volume before and after chemotherapy. A mathematical model to predict necrosis yielded a test accuracy of 75%, a sensitivity to predict necrosis of 52% and a specificity of 87%. CONCLUSIONS: Patients with pure seminoma should not undergo residual tumor resection because 97% of patients who received adequate chemotherapy were found to have no residual seminoma. In cases of nonseminoma alpha-fetoprotein values before chemotherapy less than 20 ng/ml and a high percentage of shrinkage during chemotherapy reliably predicted only 19% of cases of necrosis. Therefore, this model is clinically irrelevant and patients with minimal residual disease should undergo surgery. New methods are necessary to improve the preoperative selection of patients after chemotherapy.     

Cytoreductive surgery for advanced nonseminomatous germ cell tumors of testis

Cytoreductive surgery increases the cure rate in selected patients with advanced nonseminomatous germ cell tumor receiving chemotherapy. Complete resection of residual malignancy is a prerequisite for improving long-term disease-free survival after chemotherapy. Complete resection of residual tumor after three to four inductions with an optimal chemotherapy regimen is the current recommendation. Progression of disease on chemotherapy represents a contraindication to cytoreductive surgery. Residual malignant tissue is found in up to one third of patients with clinical evidence of residual disease after chemotherapy and currently constitutes a current indication for further chemotherapy. Incomplete resection of malignant tissue and elevated tumor markers after surgery are poor prognostic signs. Elevated serum tumor marker levels after chemotherapy and prior to surgery represent a relative contra-indication to surgery, and such patients should receive additional chemotherapy.     

Primary mediastinal nonseminomatous germ cell tumors. Results of a multimodality approach

Before cisplatin-based chemotherapy, long-term survival after resection of primary mediastinal nonseminomatous germ cell tumors was unusual. We reviewed the case histories of 48 patients who underwent multimodality treatment for mediastinal nonseminomatous germ cell tumor between 1976 and 1988. Twenty-eight patients received initial therapy at Indiana University and 20 were referred after having had unsuccessful initial therapy elsewhere. In 44 patients (92%) the levels of either one or both serum tumor markers were elevated at the time of diagnosis. Five patients had choriocarcinoma, three embryonal carcinoma, 12 yolk sac carcinoma, four teratocarcinoma, 22 mixed cell type, and two had an unclassified type. Twenty-two of the 28 patients in our initial therapy group had a complete response to treatment, as defined by normal serum tumor markers and absence of residual tumor. In this group, 16 patients had resection of residual disease after chemotherapy, four had total or near total resection before chemotherapy, and only two had chemotherapy alone. Seventeen patients are surviving after this treatment with a median survival of 64 months and a 57% 5-year Kaplan-Meier survival rate. Only two of the 20 patients who were referred for salvage chemotherapy had a complete response. Both required resection of residual disease after salvage chemotherapy. Only one patient survived after this treatment. There was no significant treatment morbidity or mortality. A multimodality approach to primary mediastinal nonseminomatous germ cell tumor with intensive cisplatin-based chemotherapy, emphasis on normalizing serum tumor markers, and aggressive resection of residual disease now offers survival to a significant number of patients.     

Late Relapse of Testis Cancer

Most relapses of germ-cell tumors occur within 2 years of initial treatment. In 2 % to 4 % of patients, relapse may occur later. The retroperitoneum is the primary site of late relapses, and alpha-fetoprotein is the predominant marker. These tumors are highly resistant to chemotherapy. Surgical resection is the preferred treatment. If the recurrent disease is inoperable, salvage chemotherapy may be instituted, followed by resection of the residual disease.     

THE FATE OF PATIENTS WITH LOCALLY ADVANCED BLADDER CANCER TREATED CONSERVATIVELY WITH NEOADJUVANT CHEMOTHERAPY, EXTENSIVE TRANSURETHRAL RESECTION AND RADIOTHERAPY: 10-YEAR EXPERIENCE

Purpose

We asses the results of bladder preservation for infiltrating cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma.

Materials and Methods

From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease.

Results

Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases.

Conclusions

Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Management of post-chemotherapy residual masses in advanced seminoma

PURPOSE: We studied the resection of post-chemotherapy residual masses (20% to 80%) of advanced seminoma complicated by extensive fibrosis, in which active disease appears in 10% to 20% of cases. MATERIALS AND METHODS: We retrospectively analyzed (1986 to 2000) residual mass evolution according to size in 79 platinum treated patients. RESULTS: There was an evaluable response in 78 patients, including toxic death in 1 after 1 chemotherapy cycle, a complete response in 34 (after chemotherapy in 15 and after complete residual mass resection in 19), a marker negative partial response in 42 (incomplete residual mass resection in 8), stable and progressive disease in 1 each. In 15 of 31 patients the resected residual mass was 3 cm. or greater, whereas in 12 of 29 it was less than 3 cm. No surgery was performed for 3 residual masses of unknown size. Of the 42 residual masses 21 disappeared at a median of 12.5 months. Progression occurred at the initial tumor site in 11 of 13 patients after a median of 3.5 months, including 3 with a complete response, 8 with a marker negative partial response (residual mass 3 cm. or greater in 3, less than 3 cm. in 4 and unknown size in 1) and treatment failure in 2 (residual mass 3 cm. or greater). At a median followup of 36.4 months 67 patients survived (no disease progression in 56 and nonevolving residual masses in 11), while 12 had died including 9 of progressive disease 1 of toxicity and 2 of other causes. CONCLUSIONS: In our study there was incomplete surgical resection in 30% of cases. Relapse in 16.6% of cases occurred rapidly after the end of chemotherapy. Viable cells were only noted in residual masses 3 cm. or greater (13%) and 50% of residual masses disappeared during surveillance. We intend to perform a prospective cohort study with close followup of patients with residual masses less than 3 cm. using an indication for surgery tailored to positron emission tomography findings in those with residual masses 3 cm. or greater.     

An evaluation of surgical treatment and chemotherapy of advanced neuroblastoma (stage III & IV) with special reference to proliferation kinetics of residual tumors

Twenty two children with advanced retroperitoneal neuroblastoma and one child with advanced posterior mediastinal neuroblastoma admitted to our clinic were treated as follows. Seven patients (group A) underwent primary resection of tumor immediately after diagnosis. In two patients of this group, the levels of VMA and HVA in urine after surgery decreased to nearly normal (group A-I), while they did not change appreciably in the other 5 patients (group A-II). Seven patients (group B) underwent resection of tumor following complete or partial response to preoperative chemotherapy. Nine patients (group C) did not undergo resection of the tumor except for exploratory laparotomy. Two group A-I patients have survived, free of disease, for 6 months and 12 months after diagnosis. All patients of group A-II died within a year. Residual tumors of 4 patients of this group began to grow explosively just after surgery, although they received persistent postoperative chemotherapy. Four patients of group B survived for more than two years and the two patients of this group who received continuous intra-arterial PGE1 therapy had no postoperative explosive growth of residual tumors. Two patients in group C survived for 20 months and the others died within a year. Primary tumors and metastatic foci responded well to therapy as compared with group A-II, which suggests that presence of primary tumors may inhibit rapid growth of metastatic foci. Resection of primary tumors, therefore, was not always conducive to survival unless residual tumor responded to postoperative chemotherapy.     

En Bloc Aortic Resection for Bulky Metastatic Germ Cell Tumors

Between 1989 and 1993, 97 patients with stages B3 and/or C nonseminomatous germ cell tumors of the testes underwent induction chemotherapy followed by retroperitoneal lymph node dissection. Of these patients 6 (ages 22 to 41 years) had gross extension of tumor into the aortic adventitia at operation, which necessitated en bloc aortic and, on 3 occasions, iliac artery resection for complete tumor removal. Aortic continuity was restored by a woven Dacron tube or bifurcated graft. All grafts were covered with omentum. There were no postoperative vascular complications. Pathological study of the residual retroperitoneal disease demonstrated that 2 patients had mature teratoma only, 2 had mature teratoma with occasional nests of immature teratoma and 2 had residual yolk sac, embryonal or choriocarcinoma elements. The latter 3 patients underwent postoperative salvage chemotherapy with varying combinations of bleomycin, etoposide, ifosfamide and cisplatin. At 4 to 55 months 4 patients were disease-free, while 2 died of metastatic disease. No problems related to the aortic reconstruction have occurred. This small experience demonstrates that, if necessary, complete surgical en bloc extirpation of bulky metastatic germ cell tumors and the aorta/iliac artery can be performed safely with a satisfactory long-term outcome.     

Results of Surgical Salvage after Failed Chemoradiation Therapy for Epidermoid Carcinoma of the Anal Canal

Background The standard treatment for epidermoid carcinoma of the anal canal consists of combined radiation and chemotherapy. For patients who present with persistent or locally recurrent disease, salvage abdominoperineal resection is the treatment of choice. The purpose of this study is to review our experience with salvage surgery in this group of patients. Methods From 1990–2002, 31 patients underwent radical salvage surgery with curative intent after failure of initial sphincter-conserving therapy, and the medical records of these patients were retrospectively reviewed. Clinicopathologic variables were determined and comparisons performed with the Cox proportional hazards model. Survival was calculated by the Kaplan–Meier method. Results Eleven patients underwent radical salvage surgery for persistent disease and 20 patients for recurrent disease. The median follow-up time was 29 months. The actuarial 5-year overall survival was 64%. Twelve patients developed recurrent disease after radical salvage surgery. Patients who received an initial radiation dose of less than 55 Gy had a significantly worse survival than those who received at least 55 Gy as part of their initial treatment (5-year overall survival 37.5% vs. 75%; age-adjusted hazard ratio 8.2 [95% CI: 1.1–59.8], P = .037). The presence of positive lymph nodes at presentation also adversely affected survival (P < .05). Factors that were not found to have an impact on survival included the presence of persistent versus recurrent disease, tumor (T) stage, and margin status of resection. Conclusions Long-term survival following salvage surgery for persistent or locally recurrent epidermoid carcinoma of the anal canal can be achieved in the majority of patients. However, patients who initially present with node-positive disease and patients who receive a radiation dose of less than 55 Gy as part of their initial chemoradiation therapy regimen have a worse prognosis after radical salvage surgery.     

Significance of salvage lymphadenectomy in the therapeutical concept of advanced nonseminomatous germ cell tumors

A retrospective study reports 65 patients with metastatic disease from nonseminomatous germ cell testicular tumors who underwent a salvage lymphadenectomy either to remove a residual mass or to confirm a complete clinical response after polychemotherapy. Scarring was found in 23 patients (35%), differentiated teratoma in 25 patients (39%) and residual cancer in 17 patients (26%). Of the 12 patients staged as complete responders 2 were found to have cancer, 4 teratoma and 6 fibrosis. Neither tumor markers nor CT scan could accurately predict which patients with residual masses would have cancer, mature teratoma or necrosis. Thus needle biopsy or limited resection is inadequate in its ability to detect persistent vital tumor. After a follow-up of 10-106 months 49 patients (75%) are living with no evidence of disease. 12 patients (19%) died of tumor progress. The most critical prognostic determinant was the nature of the tissue resected. 21 (91%) of 23 patients with only fibrous or necrotic elements are living with no evidence of disease. However, of 17 patients with persistent cancer in the resected tissue only 8 patients (47%) fared well. Our experience confirms the original concept which called for postchemotherapeutic tumor surgery in all patients who demonstrated either a partial or complete clinical response.     

Results of treatment for germ cell tumor--dose intensity of chemotherapy and residual masses after chemotherapy

We reviewed the treatment results in 44 patients with germ cell tumor and the significance of % dose intensity of Cisplatin and tumor marker half-life of induction chemotherapy and discussed the necessity of surgical resection of the postchemotherapy residual tumor. The 5-year survival rate calculated by the Kaplan-Meier method was 83.6% in total, and 95.2, 75.8 and 47.6% for good, intermediate and poor prognosis, respectively. Of the 29 metastatic cases treated by chemotherapy, 5 (17.2%) achieved complete response (CR) and 15 (51.7%) partial response, and % dose intensity of Cisplatin were 75.4% in total and 86.4 +/- 8.6, 71.6 +/- 11.1, 84.3 +/- 8.3 and 62.2 +/- 11.0% in CR, PR, NC and PD. Dose intensity was correlated with the clinical response and the prognosis. Of the 12 PR cases without teratoma elements, two had salvage surgery, five had additional chemotherapy and five were followed by surveillance. One case followed by surveillance died of the disease, another one with additional chemotherapy was alive with the disease and the others were alive with no evidence of disease. Surgical resection is an effective treatment to remove residual masses, but observation may also be considered in the cases without teratoma elements.     

Should aggressive surgery ever be part of the management of small cell lung cancer?

CMT with surgery and chemotherapy is feasible, the toxicity is manageable, and postoperative morbidity and mortality rates are acceptable. Patient selection is important, and the results of the LCSG trial indicate that surgical resection will not benefit most patients who have limited SCLC. The chances of long-term survival and cure are strongly correlated with pathologic TNM stage. Consideration of surgery for patients who have SCLC should be limited to those with stage I disease and perhaps some patients with stage II tumors. Therefore, before surgery is undertaken, patients should undergo extensive radiologic staging with CT, MRI, and perhaps even positron emission tomographic scanning and mediastinoscopy, even if the radiologic assessment of the mediastinum is negative. Surgery may be considered for patients with T1-T2 NO SCLC tumors, and whether it is offered as the initial treatment or after induction chemotherapy remains controversial [40,43]. If SCLC is identified unexpectedly at the time of thoracotomy, complete resection and mediastinal lymph node resection should be undertaken, if possible. Chemotherapy is recommended postoperatively for all patients, even those with pathologic stage I tumors. Surgery likely has very little role to play for most patients with stage II disease and virtually no role for patients with stage III tumors. Even though chemotherapy can result in dramatic shrinkage of bulky mediastinal tumors, the addition of surgical resection does not contribute significantly to long-term survival for most patients, as shown conclusively by the LCSG trial. The final group of patients who may benefit from surgical resection are those with combined small cell and non-small cell tumors. If a mixed-histology cancer is identified at diagnosis, the initial treatment should be chemotherapy to control the small cell component of the disease, and surgery should be considered for the non-small cell component. For patients who demonstrate an unexpectedly poor response to chemotherapy, and for patients who experience localized late relapse after treatment for pure small cell tumors, a repeat biopsy should be performed. Surgery may be considered if residual NSCLC is confirmed.     

Chemotherapy of disseminated germ cell tumors

The fact that germ cell tumors can be successfully managed puts an extraordinary burden on the physician and health care system to ensure that the promise of cure is achieved in all patients except the small proportion that present with advanced refractory disease. Good risk disseminated disease should be treated with three cycles of bleomycin, etoposide and cisplatin (BEP) whereas those with more advanced disease should receive four cycles. Postchemotherapy resection of residual disease is commonly required. In patients in whom disease recurs after primary chemotherapy, salvage treatments can result in cure in 30–40% of patients. Physicians managing these patients should be aware of some of the pitfalls encountered when determining relapse and should be versed in the indications for salvage conventional dose chemotherapy, high dose chemotherapy, and the role of aggressive desperation surgery.     

Salvage surgery following downstaging of unresectable hepatocellular carcinoma

OBJECTIVE: We reported here a series of 49 patients with unresectable hepatocellular carcinoma (HCC) who underwent nonsurgical treatment to downstage the disease followed by salvage surgery, their long-term outcome, and pattern of recurrence. SUMMARY BACKGROUND DATA: Most HCC patients present with unresectable disease and are treated with chemotherapy or intra-arterial therapy with a palliative intent. Occasionally, there are good responses to treatment so that salvage surgery becomes feasible afterward. However, long-term outcomes of these patients are seldom reported. METHODS: Patients with unresectable hepatocellular carcinoma, from September 1993 to June 2002, who received salvage surgery after downstaging by systemic chemotherapy, intra-arterial yttrium-90 microspheres, or sequential treatment were included in this study. Systemic chemotherapy consisted of combination doxorubicin, cisplatin, interferon-alpha and 5-fluorouracil (5-FU), or single-agent doxorubicin. The choice of treatment was according to stage of disease and contemporary clinical trial protocol. Survival, recurrence pattern, and surgical outcome were studied. RESULTS: There were 49 patients in this study with 40 males and 9 females, age ranged from 12 to 69 years. Forty patients (81.6%) were hepatitis B positive. Thirty-two patients had combination chemotherapy alone (65.3%), 8 patients had single agent chemotherapy alone (16.3%), 4 patients received intra-arterial yttrium-90 microspheres alone (8.2%), and 5 patients received sequential therapy (10.2%). Twenty-eight (57.1%) patients received major hepatic resection. Thirteen patients (26.5%) had complete necrosis of the tumor after treatment. Twenty-one patients (42.9%) had recurrence after surgery, and 14 of them were intrahepatic recurrence. The median survival was 85.9 months. The 1-year, 3-year, and 5-year survival rates were 98%, 64%, and 57%, respectively. CONCLUSIONS: Salvage surgery after successful downstaging can provide long-term control of disease in a small proportion of patients with unresectable hepatocellular carcinoma.     

Persistent cancer in postchemotherapy retroperitoneal lymph-node dissection: outcome analysis

Summary Surgery following chemotherapy for treatment of metastatic testis cancer is reserved for partial remissions with localized tumors considered resectable. After primary chemotherapy, about 90% will have teratoma or necrosis and only 10% will have cancer. The concept of two cycles of post operative chemotherapy in this small group with cancer is supported by a 70% long term cure rate. A more difficult group of patients are those who have had not only primary but also salvage chemotherapy for refractory tumor. About 55% of these patients undergoing post (salvage) chemotherapy RPLND surgery have persistent cancer in the resected specimen. There is no data to support the routine use of repeat salvage chemotherapy post operatively. Of 91 patients presenting for surgery post salvage chemotherapy, 53 were considered completely resected and 36 incompletely resected. Of the 53 realistic candidates for cure with complete resections, 25 were given post operative repeat salvage chemotherapy and 28 received none. 9 (36%) receiving more chemotherapy remained NED and 12 (43%) receiving none remained NED. 12 in each group died of disease. Therefore, there is no data to support routine repeat salvage chemotherapy in patients considered completely resected who had already received salvage chemotherapy pre-operatively. Rather the outcome in this cohort depends more on the completeness of its resectability.     

Primary mediastinal nonseminomatous germ cell tumors: the influence of postchemotherapy pathology on long-term survival after surgery.

OBJECTIVES: The treatment of nonseminomatous germ cell tumors with cisplatin-based chemotherapy followed by aggressive surgical resection of residual disease is one of the most successful models for multimodality cancer therapy. We reviewed the case histories of 91 patients treated at our institution from 1981 to 1998 with primary mediastinal nonseminomatous germ cell tumors to evaluate variables that may influence survival after surgery. METHODS: Twelve of the 91 patients did not undergo postchemotherapy resection because of progressive disease. Seventy-nine of them underwent 82 thoracic surgical procedures and are the basis of this review. The majority (71/75) had elevated serum tumor markers, 75% (n = 50) of which returned to normal levels after first- or second-line chemotherapy. RESULTS: There were 3 operative deaths and 1 late death, attributed to pulmonary complications. Twenty-four patients died of recurrent disease and 3 of leukemia, for an overall survival of 61% after an average follow-up of 48 months. The pathologic findings of complete tumor necrosis (n = 19) and benign teratoma (n = 28) in the surgical specimen predicted excellent and good long-term survival, respectively, which was statistically better than that of patients having persistent nonseminomatous germ cell tumors (n = 24) or carcinomatous/sarcomatous degeneration (n = 8). CONCLUSIONS: Primary nonseminomatous germ cell tumors of the mediastinum can be cured with a multimodality therapy, particularly in the subset of patients with postchemotherapy pathologic findings of tumor necrosis and teratoma. Survival is poor but possible in patients with unfavorable pathologic findings after chemotherapy, currently justifying an aggressive surgical approach in patients with otherwise operable disease.     

The significance of resections for residual masses after chemotherapy in metastatic testicular tumors

BACKGROUND: After chemotherapy for metastatic testicular tumors, masses may remain, often in the metastatic sites. This study analyses the role of resections for the residual masses. METHODS: Seventy-seven patients with advanced (stage II, III) testicular tumors were treated. Of these, 38 patients, including eight with seminoma and 30 patients with non-seminomatous germ cell tumors, underwent resection of residual masses after chemotherapy and have been followed for a median of 41.5 months (range 2-138) after the resection. RESULTS: Residual masses were necrosis/fibrosis in 19 patients, mature teratoma in 11 and cancer in eight. The ratio of cancer in stage III (41.2%) was significantly higher than that in stage II (4.8%). Ten of 38 (26.3%) patients experienced recurrences in sites other than the resected sites, and five of 10 patients have died of cancer. Most recurrences (80%) occurred within two years. Recurrences after resection were detected in 4.8% of stage II patients, 52.9% of stage III, 16.7% of necrosis/fibrosis and mature teratoma, and 62.5% of cancer. The survival rate of patients with cancer was significantly lower in spite of adjuvant chemotherapy after surgery. CONCLUSIONS: Resection for residual masses after chemotherapy in metastatic testicular tumors was useful in confirming the tissue and in controlling the metastatic sites. Recurrences were often found in patients with cancer in the residual mass and the prognosis of patients with cancer was poor, therefore the development of more effective therapy for patients with cancer is required to improve the prognosis.