Surveillance For Clinical Stage Research Articles

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.

Utility of annual screening serum testosterone level in men on surveillance for clinical stage I testicular cancer.

144 Background: Testicular cancer occurs in young men and is usually cured leaving survivors with many life years at risk from long term treatment effects. Risks increase with treatment intensity and include cardiovascular disease associated with the metabolic syndrome (Haugnes 2012, de Haas 2013). Testosterone deficiency (TD) is associated with metabolic syndrome &amp; reduced QoL (Huddart 2005). Serum testosterone levels (STLs) are also influenced by underlying testicular dysgenesis &amp; the effects of ageing (Skakkebaek 2001, Oldenburg 2016). We added annual screening STL to our surveillance protocols in 2013 &amp; reviewed the value of this practice. Methods: Men followed in our Testicular Surveillance Clinic from 01 Jan 2006 to 31 Dec 2015 were identified electronically &amp; data extracted retrospectively. Men eligible for this analysis had clinical stage I (CS I) testicular cancer treated with unilateral orchiectomy alone. Outcomes of interest were STLs, Endocrinology referral (Endo) &amp; treatment with androgen replacement therapy (ART). TD was defined by 3 cutoffs of most recent screening STL: &lt; 8.6 nmol/L [age 20-49] (or &lt; 6.7 nmol/L [age &gt; 50]) (local laboratory), &lt; 10.1 nmol/L (Huddart 2005), or &lt; 12.1 nmol/L (EAA &amp; EAU). Results: 77 eligible men were identified: median age 34 years (range, 15-65), seminoma/nonseminoma/mixed/other (45/27/4/1). By the 3 STL cutoffs, TD was present in 13 (16.9% [95%CI, 9.3-27.1%), 22 (28.6% [18.8-40.0%] &amp; 37 (48.1% [36.5-59.7%]); respectively. Nine men (11.4%) were referred to Endo, 1 had morning STL pending &amp; 1 was using OTC ART. Of 8 men assessed by Endo, 5 (6.5%) were prescribed ART. Six men had no screening STL done (3 nonadherent, 1 prostate cancer &amp; 2 unknown). Two men were discharged from clinic with unequivocal low STL. Conclusions: Annual screening STL appears to be useful and may be necessary. 15 CS I men (19.5%) in our clinic had unequivocal TD &amp;/or were referred to an Endo. An additional 20 men (26%) had STLs in a range associated with reduced QoL. Almost half had STLs considered suitable for ART in the presence of symptoms. Two men (2.6%) were discharged with low STLs unaddressed. Guidelines for the optimal assessment and management of men with positive screening for TD are needed.

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer

BackgroundPatients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. ObjectiveTo determine cRR in CSI testicular cancer. Design, setting, and participantsWe reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. Outcome measurements and statistical analysiscRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. Results and limitationsAt orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size <3cm, respectively. However, for patients without relapse within the first 2 yr of follow-up, the corresponding risk of relapse within the next 5 yr in the groups was 0.0%, 1.0% (95% confidence interval [CI] 0.3–1.7%), 5.6% (95% CI 3.1–8.2%), and 3.9% (95% CI 1.4–6.4%). Over time, cRR decreased (p≤0.021) in all models. Limitations include changes to surveillance protocols over time and few late relapses. ConclusionsAfter 2 yr, the risk of relapse on surveillance for CSI testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Patient summaryOur study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time.

Outcomes of progression on surveillance for clinical stage I nonseminomatous germ cell tumours (NSGCT).

377 Background: Active surveillance (AS) is universally accepted for clinical stage (CS) IA and favoured by most centers for CSIB. Patients progressing on AS are typically treated with chemotherapy, but there is no consensus. We describe patterns and mode of detection of progression and treatment of progression in our NSGCT AS cohort. Methods: From Dec 1980 to Aug 2011, 466 CSI NSGCT patients were managed with AS and 133 (28%) had disease progression while on AS. Treatment upon progression was physician choice but based on site of progression (e.g. retroperitoneum vs. extra-retroperitoneal), size or multifocality, and markers (S0 or stable, low level S1 vs. ≥ S1). Mode of detection of progression, characteristics at progression and primary treatment of progression (chemotherapy vs. retroperitoneal lymphadenectomy (RPLND)) were explored. Multivariate logistic regression was used to explore factors associated with receipt of more than one therapy in treatment of progression after surveillance. Results: Median time to progression was 7.3 months and detected by routine imaging (47%), routine serum tumour markers (37%), or both (12%). Progression most frequently occurred in the retroperitoneum (67%). Following progression, first-line treatment was chemotherapy for 71 (53%), RPLND for 51 (38%) and 11 (8.3%) underwent other therapy. In 59%, only one modality of treatment was required: chemotherapy only in 42/71 (59%); RPLND only in 36/51 (71%). For those treated with chemotherapy, pure embryonal carcinoma in the orchiectomy pathology (OR 0.11; p=0.05) was inversely associated with requiring further therapy. For those treated with RPLND, elevated markers pre-RPLND (OR 7.31; p=0.01) was associated with requiring further therapy. Overall, a second relapse occurred in 25/133 (19%) patients. With a median follow-up of 8.2 years, there were 5 deaths from testis cancer (3.8% of AS progressors; only 1.1% of overall AS cohort). Conclusions: The majority of patients progressing on surveillance do so in the retroperitoneum and within the first year. Of those that progress, most will achieve complete response with single modality treatment. In particular, RPLND can be utilized as monotherapy in select cases.

Cutting Back on Computed Tomography Scan Frequency in Curative Oncology: Get the Picture

Cutting Back on Computed Tomography Scan Frequency in Curative Oncology: Get the Picture

Carboplatin for Stage I Seminoma and the Sword of Damocles

Damocles lived on the island of Sicily approximately 400 BC and served in the court of Dionysius II of Syracuse. As told by Cicero in the Tusculan disputations, Damocles was extremely effusive of the tyrant Dionysius and continuously told him how fortunate he was to have great power and riches. Growing weary of these comments, Dionysius one day asked Damocles if he would like to sample his lifestyle. Damocles happily agreed and was subsequently treated to a bountiful banquet that included the finest foods, wines, flowers, and music. At the end of the meal he glanced up and saw a sharp sword dangling by a single horsehair above his head. Damocles quickly left the banquet, suddenly quite content with his former life. “The Sword of Damocles” has grown to describe the feeling of impending doom. In this issue of the Journal of Clinical Oncology, Aparicio et al have used this metaphor for the stress of the long follow-up experienced by patients during surveillance for clinical stage I seminoma. In their article, the authors report their well-conducted phase II study of a so-called riskadapted strategy in which patients with clinical stage I (a tumor that is apparently confined to the testicle, with normal serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein and normal computed tomography of the chest, abdomen, and pelvis) seminoma were assigned to either surveillance or chemotherapy with carboplatin. Recently, the management of clinical stage I seminoma has become controversial. Is the stress of long follow-up and good compliance eliminated by this approach? In our opinion, the answer is no, as relapses still occur at a rate that may be worse than that observed with standard radiation therapy (RT) and at sites that are different. RT has been the standard primary treatment for clinical stage I seminoma for several decades. After approximately 20 to 25 Gy administered to the retroperitoneal and ipsilateral pelvic lymph nodes (the so-called dog-leg port), the overall recurrence rate is approximately 3% to 5%, and virtually all relapses occur outside the RT portal. The 5-year overall survival rate for patients with stage I seminoma after RT is nearly 100%. Late complications from RT, such as nontesticular second malignancies and cardiovascular disease, have been well described. In the past two decades, surveillance alone has been studied as an alternative approach to the management of patients with clinical stage I seminoma. The relapse rate after orchiectomy alone is approximately 15% to 20%. Investigators at the Princess Margaret Hospital (Toronto, Canada) led the efforts. In a series of 471 patients seen between 1981 and 1994, relapses occurred in 37 patients (16%) on surveillance and in 14 patients (5.7%) treated with RT, with a 5-year actuarial survival rate of 97% and a cause-specific survival rate of 99.8% for those managed with RT (n 245) or surveillance (n 226), respectively. Because most patients on surveillance experienced relapse in the retroperitoneum and received therapeutic RT, only 13 patients (5.7%) on surveillance and 10 patients receiving prophylactic RT required subsequent chemotherapy. Hence all of the patients who experienced relapse were cured with either subsequent RT or chemotherapy. With the success of chemotherapy in patients with disseminated germ cell tumors (GCTs), the role of systemic chemotherapy has been studied in seminomas. Noting that seminoma may be more chemotherapy sensitive than its nonseminomatous counterpart, some investigators have advocated single-agent carboplatin over combination therapy. The report by Aparicio et al from the Spanish Germ Cell Cancer Cooperative Group is one such study. An interesting feature of this article is the investigation of not only the assignment of two cycles of carboplatin as adjuvant therapy for a high-risk and surveillance for a lowrisk group of patients with clinical stage I seminoma, but also the prospective use of a risk algorithm to assign highrisk or low-risk status to this patient population. These risk JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 34 DECEMBER 1 2005

Cost- and risk-benefit considerations in the management of clinical stage I nonseminomatous testicular tumors.

The high curability of clinical stage I nonseminomatous germ cell tumors (NSGCTs) and the availability of equally effective management options (retroperitoneal lymph node dissection [RPLND] and surveillance) allows for treatment decisions based on secondary end points, including sort- and long-term toxicity and cost relative to benefit. The purpose of this study was to perform cost-benefit and risk-benefit analyses of management options in clinical stage I NSGCT using data from the literature and Indiana University. The overall costs for 100 patients undergoing a primary RPLND were compared with the total costs of 100 patients managed by surveillance for clinical stage I disease. These two options were then analyzed in terms of survival, late relapse, acute and chronic toxicity (including fertility), and perioperative morbidity. The overall costs of these two approaches were essentially identical. The two options were similar in terms of survival, although RPLND demonstrated superiority in terms of fertility, toxicity, and late relapse. The choice of nerve-sparing RPLND or surveillance in clinical stage I NSGCT patient cannot be made on the basis of cost as a discriminator. Instead, the decision should be made based on patient desires, physician expertise, biological predictors, and short- and long-term toxicity.

Surveillance for clinical stage I nonseminomatous testis carcinoma: rationale and results.

Surveillance protocols for clinical stage I nonseminomatous germ cell tumors of the testis have demonstrated that using current staging methods, approximately 75% of clinical stage I patients can be cured with orchiectomy alone. With treatment of patients who relapse, the overall outcome with surveillance is similar to that of standard therapy. Retrospective analysis of clinical and pathologic parameters appears to identify a subgroup of patients with a very low risk of relapse. If confirmed in prospective studies, this low-risk group will be well suited for orchiectomy with subsequent observation. The remainder of patients have an intermediate (40-60%) risk of relapse. How these remaining patients are best managed is a subject of controversy. The resolution of this controversy will likely require substantial improvement in the methods for predicting relapse, or substantial reductions in the patient burden of surgical and chemotherapeutic treatment.

Selecting initial therapy. Seminoma and nonseminoma.

About 80% of seminoma presents as low-stage disease. If clinical studies are negative, the usual initial therapy is "prophylactic" radiotherapy to the retroperitoneal zone. If clinical Stage II disease is evident, radiotherapy versus primary chemotherapy is being studied. Primary chemotherapy is treatment of choice for clinical Stage III disease. Postchemotherapy radiographic lesions are safe to follow without surgical extirpation as they are usually necrotic. Surveillance for clinical Stage I disease is another option. For nonseminoma, clinical Stage I disease has been managed with staging RPLND. But 70% of such cases will have negative nodes. Hence, primary surveillance studies are under way, with chemotherapy reserved for those who relapse clinically (estimated 95% survival). Sadly, surveillance has not been effective when applied on an ad hoc basis at the community level. Problems are compliance, delayed detection of relapse, nonreporting of failures. Clinical Stage II disease is managed with RPLND. Adjuvant, limited postoperative chemotherapy is an option versus no postoperative chemotherapy followed by full chemotherapy for those who relapse as Stage III disease later. Another option under study for Stage II disease is primary chemotherapy with RPLND surgery reserved for those who achieve only a partial remission.