Testis cancer is the most common solid malignancy in young males. The purpose of this guideline is to provide a useful reference on the effective evidence-based treatment of early stage testicular ...cancer.
The systematic review utilized to inform this guideline was conducted by a methodology team at the Johns Hopkins University Evidence-based Practice Center. The methodology team searched using PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The evidence review team also reviewed relevant systematic reviews and references provided by the panel to identify articles that may have been missed by the database searches.
When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions.
This guideline attempts to improve a clinician's ability to evaluate and treat patients with testicular cancer, but higher quality evidence in future trials will be essential to improve level of care for these patients.
Abstract Objective To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with noncastrate metastatic prostate ...cancers that are incurable with single modality therapy. Patients and Methods Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease and/or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary endpoint was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease. Results Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval 3-38%) achieved the primary endpoint, which persisted for 5, 6, 27+, and 46+ months. All patients meeting the primary endpoint had been classified with M1b disease at presentation. Conclusion A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The endpoint of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and shifts the paradigm from palliation to cure.
We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel T plus ifosfamide I followed by high-dose carboplatin C plus etoposide E with stem-cell support) in germ cell ...tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.
Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response IR to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.
Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.
TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
The efficacy of paclitaxel was evaluated in combination with ifosfamide and cisplatin as second-line chemotherapy for patients with relapsed testicular germ cell tumors (GCTs).
Forty-six patients ...with progressive metastatic GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. Eligibility required that patients have both a testis primary tumor site and a prior complete response (CR) to a first-line chemotherapy program, which had been identified previously as favorable prognostic factors to conventional-dose salvage chemotherapy.
Thirty-two (70%) of 46 patients achieved a CR to treatment. Three patients (7%) who achieved a CR relapsed after TIP chemotherapy. Twenty-nine patients are continuously disease free at a median follow-up time of 69 months, resulting in a 63% durable CR rate and a 2-year progression-free survival rate of 65% (95% CI, 51% to 79%).
Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.
To evaluate the safety and efficacy of percutaneous peritoneovenous shunt (PPVS) placement in treating intractable chylous ascites (CA) in patients with cancer.
Data from 28 patients with refractory ...CA treated with PPVS from April 2001 to June 2015 were reviewed. Demographic characteristics, technical success, efficacy, laboratory values, and complications were recorded. Univariate and multivariate logistic regression analysis was performed.
Technical success was 100%, and ascites resolved or symptoms were relieved in 92.3% (26 of 28) of patients. In 13 (46%) patients with urologic malignancies, whose ascites had resulted from retroperitoneal lymph node dissection, the ascites resolved, resulting in shunt removal within 128 days ± 84. The shunt provided palliation of symptoms in 13 of the remaining 15 patients (87%) for a mean duration of 198 days ± 214. Serum albumin levels increased significantly (21.4%) after PPVS placement from a mean of 2.98 g/dL ± 0.64 before the procedure to 3.62 g/dL ± 0.83 (P < .001). The complication rate was 37%, including shunt malfunction/occlusion (22%), venous thrombosis (7%), and subclinical disseminated intravascular coagulopathy (DIC) (7%). Smaller venous limb size (11.5 F) and the presence of peritoneal tumor were associated with a higher rate of shunt malfunction (P < .05). No patient developed overt DIC.
PPVS can safely and effectively treat CA in patients with cancer, resulting in significant improvement in serum albumin in addition to palliation of symptoms.
The aim of this phase II study was to determine the efficacy of gemcitabine administered as an intravesical agent in patients with bacille Calmette-Guérin (BCG) -refractory transitional cell ...carcinoma of the bladder.
Patients with superficial bladder cancer refractory or intolerant to intravesical BCG therapy and refusing a cystectomy were considered eligible for the trial. Eligible patients received two courses of intravesical gemcitabine twice weekly at a dose of 2,000 mg/100 mL for 3 consecutive weeks, with each course separated by 1 week of rest. Patients were evaluated for response at 8 weeks, then every 3 months to 1 year.
Thirty eligible patients were included on study. The median follow-up for all the patients was 19 months (range, 0 to 35 months). Of the 30 patients, 15 (50%; 95% CI, 32% to 68%) achieved a complete response (CR). Twelve patients had tumor recurrence with a median recurrence-free survival time of 3.6 months (95% CI, 2.9 to 11.0 months). Two patients maintained a CR at 23 and 29 months, respectively. The 1-year recurrence-free survival rate for patients with a CR was 21% (95% CI, 0% to 43%). Two patients progressed to a higher stage while receiving gemcitabine treatment. The median follow-up for patients who did not have a progression or a cystectomy was 19 months (range, 2 to 35 months). Eleven patients (37%) underwent a cystectomy subsequent to gemcitabine therapy.
Gemcitabine has activity in a high-risk patient population and remains a viable option for some patients who refuse cystectomy.
Purpose We evaluated pathological variables of testicular sex cord-stromal tumors, management options and clinical outcomes. Materials and Methods We retrospectively reviewed the records of 48 ...patients with testicular sex cord-stromal tumors treated at Memorial Sloan-Kettering Cancer Center between 1997 and 2012. Clinical outcomes were compared based on treatment and previously described pathological factors associated with metastatic potential. Results Of the 48 patients 37 underwent surveillance without retroperitoneal lymph node dissection, including 34 with no high risk feature and 3 with 1. Median followup was 14.5 months (IQR 6.9–32.5). No patient experienced recurrence. Retroperitoneal lymph node dissection was performed in 11 patients, including 6 with clinical stage I disease and 2 or more high risk features who underwent early dissection, 2 with clinical stage IIa disease at diagnosis who underwent early dissection and 3 with clinical stage I disease and 2 or more high risk features who were observed elsewhere but referred to our institution due to retroperitoneal disease. Six patients with clinical stage I disease underwent early dissection, 4 had no evidence of disease at a median followup of 6.6 years and 2 experienced recurrence and died of disease. Neither of the 2 patients with IIa disease at diagnosis experienced relapse. All 3 patients with delayed dissection experienced relapse and 1 died of disease. Conclusions Patients with testicular sex cord-stromal tumors and 1 or no high risk feature can be safely observed without retroperitoneal lymph node dissection but longer followup is needed. Given the lack of effective alternative treatments, early retroperitoneal lymph node dissection may be beneficial in those with 2 or more high risk features, or clinical stage IIa disease.
Abstract Objectives To characterize the incidence, presentation, management, and relapse of a large population of bilateral testicular germ cell tumors (TGCT) from a single institution. Methods We ...identified bilateral TGCT diagnosed between 1/1989 and 2/2014. We categorized synchronous and metachronous TGCT, noting time between 1st and 2nd TGCT, histology seminoma vs. nonseminoma (NSGCT), stage and treatments. Kaplan Meier survival estimates characterized relapse. Results Of 5,132 TGCT patients, 128 (2.5%) had bilateral TGCT. Bilateral TGCT increased over time–1.7% in 1989-1994 up to 3.8% in 2010-2/2014. The 35 (27%) synchronous TGCT had 20 (57%) concordant seminoma, 5 (14%) concordant NSGCT, and 10 (29%) discordant. The 93 (73%) metachronous cases had median time interval to 2nd TGCT of 73 months (range 5 months to 28.6 years). Compared to 1st TGCT, 39 (42%) had discordant histology, 29 (31%) concordant seminoma, and 25 (27%) concordant NSGCT. Stage at 1st tumor was statistically similar to second TGCT (2nd stage I/II/II in 69%/22%/10%). Increasing duration between 1st and 2nd TGCT was not associated with higher stage (II/III) at second TGCT (p=0.09). Treatment at 1st tumor was not associated with stage at 2nd tumor. Relapse following bilateral diagnosis was 16.8% (95%CI 10.5-26.2%) at 5 years. Conclusions Incidence of bilateral TGCT increased with >25% of metachronous TGCT presenting ≥10 years after 1st TGCT; possible causes include increased survivorship and/or referral bias. Stage was statistically similar at 1st and 2nd tumor; stage at 2nd tumor was not associated with time interval between tumors or prior treatment modality at 1st tumor.
Modified template retroperitoneal lymph node dissections (RPLND) have become increasing applied in the postchemotherapy (PC) setting. We evaluated our experience with PC-RPLND to determine the ...incidence of disease extending outside the boundaries of a modified PC-RPLND.
From 1989 through 2003, a total of 532 men underwent PC-RPLND for metastatic nonseminomatous germ cell tumor (NSGCT). Of these, 269 (51%) had either viable germ cell tumor (GCT) or teratoma present in the RPLND specimen. After Institutional Review Board approval, clinical and pathologic data were obtained from our prospective surgical database. The incidence of retroperitoneal disease outside the boundaries of five modified templates was reported for the presence of viable GCT or teratoma.
Of the 269 patients with viable GCT or teratoma, 20 to 86 (7% to 32%) patients had evidence of extratemplate retroperitoneal disease, depending on the boundaries of the modified template. There was no difference in the histologic distribution for patients with disease confined to or outside of the modified templates. Despite the absence of preoperative radiographic evidence of disease outside the boundaries of the Testicular Tumor Study Group template, the incidence of extratemplate metastasis for men with residual retroperitoneal masses less than 1, 1 to 2, 2 to 5, and more than 5 cm was two of 24 (8%), seven of 38 (18%), 27 of 92 (29%), and 14 of 55 (25%), respectively.
Our data suggest a bilateral RPLND is a prudent approach for the management of men with metastatic NSGCT after chemotherapy, given that at least 7% to 32% of men will have teratoma or viable GCT outside the boundaries of a modified template.
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