postchemotherapysurgeryforgermcelltumors...

Genitourinary Cancer: Renal, Bladder, and Testicular

Postchemotherapy Surgery for Germ Cell Tumors—What HaveWe

Learned in 35 Years?STEPHEN B. RIGGS,a,b EARL F. BURGESS,a KRIS E. GASTON,a,b CAROLINE A. MERWARTH,a DEREK RAGHAVANaaLevine Cancer Institute and bMcKay Department of Urology, Carolinas Healthcare System, Charlotte, North Carolina, USADisclosures of potential conflicts of interest may be found at the end of this article.

Key Words. Retroperitoneal lymph node dissection x Testicular cancer x Postchemotherapy retroperitoneal lymph node dissection x

Seminoma x Nonseminoma x Germ cell tumor

ABSTRACT

Postchemotherapy surgery for advanced testicular cancer hasevolved over the last couple of decades. Patients withnonseminomatous germ cell tumors and residual retroperito-neal mass $1 cm should undergo postchemotherapy retro-peritoneal lymph node dissection (RPLND). For seminoma,RPLND is considered in those patientswithmasses$3 cm thatare also positron emission tomography positive. Masses thatoccur outside of the retroperitoneum should be completely

resected with the possible exception of bilateral lung masseswhen resection of the first mass shows necrosis. The role ofsurgery in patients with extragonadal germ cell tumors ismostvital in those with primary mediastinal nonseminomatousgerm cell tumors. Importantly, patient selection, surgicalplanning, and consideration of referral to centers with thisexpertise are important to optimize success. The Oncologist2014;19:498–506

Implications for Practice: Patients with advanced testicular cancer will often be considered for surgical consolidation followingchemotherapy. This review article focuses on the evaluation and role of surgery in treatment of these complex patients. Itunderscores the selection of patients, vital role of surgery, as well as providing guidance in the use of surveillance as opposed tosurgical extirpation.

INTRODUCTION

The role of surgery following primary chemotherapy fortesticular cancer has evolved over the past 3 to 4 decades.Since the 1970s, there has been exploration of salvage surgeryfor those who do not achieve complete response tochemotherapy and even to consolidate successful chemother-apy by removing occult residual foci of germ cellmalignancy orteratoma. Furthermore, it has becomeapparent that germ celltumor can have transformation (either as a side effect oftreatmentordue tobenignevolution) tomatureteratomathatis inherently chemotherapy-resistant [1].

Our senior author and colleagues reported from the RoyalPrince Alfred Hospital group its experience from 1977 to 1980involving 21 patients (mix of stage II and III) who failed toachieveaclinical or radiological response (CR), ofwhom14hadretroperitoneal node dissections, 5 had biopsy only, and 2 hadthoracotomies for residual disease outside the retroperito-neum [2]. Several important observations were evident fromthis early series: first, the surgery was complex, requiring anaverage of 7 hours and at times requiring resection of adjacentorgans. Second, thosepatientswith tumormarkers elevatedatdiagnosis and after primary chemotherapy either relapsed orhad viable carcinoma at the time of surgery. Next, thosepatients with positive prechemotherapy tumor markers who

subsequently normalized had a low probability of eitherrelapse or viable carcinoma following surgery. In addition,multiple residual sites (e.g., lung, supraclavicular node, andretroperitoneum) did not necessarily have concordant pathol-ogy (i.e., one site could have necrosis and the other site viablegerm cell tumor or teratoma) [2]. Other early series confirmedthe prognostic importance of a good response to chemother-apy, marker status after induction chemotherapy, and tissuetype in resected specimen. Finally, those with residual viablediseasehave thepotential foradverseoutcomesandshouldbeconsidered for further chemotherapy [3–5]. It is our intent inthis article to update the oncologist regarding the role ofsurgery after chemotherapy for advanced germ cell tumors.

IMAGING AFTER CHEMOTHERAPY

In nonseminomatous germ cell tumors (NSGCTs), the imagingof choice is usually computed tomography (CT), withfludeoxyglucose (FDG) positron emission tomography (PET)reserved for residual masses in seminomatous patients only.One complicating factor surrounding the use of FDG PET forevaluation inpatientswithNSGCTs is due to thepossibility thatany residual mass could contain viable tumor, teratoma, orfibrosis/necrosis/inflammation/fluid.Therefore, apositivePET

Correspondence: StephenB. Riggs,M.D.,McKayDepartment ofUrology, Levine Cancer Institute, CarolinasHealthcare System, 1021MoreheadMedicalDrive,Suite6100,Charlotte,NorthCarolina28204,USA.Telephone:980-442-6410;E-Mail:[email protected] ReceivedOctober1,2013; accepted for publication January 23, 2014; first published online in TheOncologist Express on April 9, 2014.©AlphaMed Press 1083-7159/2014/$20.00/0 http://dx.doi.org/10.1634/theoncologist.2013-0379

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scan in this population could represent viable germ cell orbenign inflammation; fibrosis/necrosis and mature teratomado not have affinity for the radiolabeled tracer unless theycontain pockets of tissue fluid that allow passive absorptionand retention of tracer. However, after chemotherapy forseminomatous tumors, there is only binary choice for thehistology of the remaining mass: viable germ cell cancer orfibrosis, of which the latter appears to be much less “PET-active” [6].

The use of FDG PET in those patients with pure seminomaand especiallymasses.3 cm appears to have utility. De Santiset al. published a multicenter study involving 51 patients inwhom19 had residualmasses.3 cmwith amedian follow-upof 34 months [7]. The positive predictive value and negativepredictive value of FDG PET, irrespective of tumor size, were100%and96%, respectively.The two falsenegativeswere seenin tumors#3cm in size. Size.3cmor#3cmwasconfirmed tobe apredictor of residual disease, as it has been in other series,with a cancer rate of 37% and 8%, respectively [7–10]. Thisseries was followed up 1 year later and reported an additionalfalse negative (3 of 11) in tumors ,3 cm but maintained itsperfect positive predictive value for a final sensitivity andspecificity of 80% and 100%, respectively [11]. Therefore, allpostchemotherapy masses .3 cm in size in patients withprimary seminoma do not necessarily need treatment. Apositive PETscan strongly suggests tumor (requiring additionaltherapy); therefore, we recommend the use of PET CT in thissetting. Finally, it is worth mentioning that the timing of FDGPET after chemotherapy should be between 4 and 12 weeks,but noearlier becauseof thepotential for inflammation-basedfalse-positive results [7].

RETROPERITONEAL LYMPH NODE DISSECTION

Retroperitoneal lymphnodedissection (RPLND) (Fig. 1)was firstperformed in the 1950s using knowledge from lymphaticdrainagestudiesderivedmanyyearsearlier.Theprimary landingzoneswere furtherelucidatedanddeterminedtobepredictablein subsequent studies [12–14]. In general, as evidenced fromearly studies involving RPLND in patients without priortreatment, right-sided tumors metastasize to the interaorto-caval lymph nodes first (just below the left renal vein), followedby theprecaval andparacaval lymphnodes. Left-sided testiculartumors metastasize to the para- and preaortic areas. Contralat-eral involvement is more frequent in right-sided tumors as wellas in bulky retroperitoneal disease [12, 15].The involvement ofsuprahilar zones is infrequent in patients with minimal tomoderate retroperitoneal disease (old staging B1; currentstaging IIA), but this incidence increases with increasingretroperitoneal volume (old staging B1, B2; current staging IIB,IIC). Furthermore, ipsilateral or contralateral disease below thebifurcation of the internal iliac vessels seems to be present onlyin the setting of more bulky retroperitoneal adenopathy (stageIIB, IIC) [12]. Enthusiasm for a modified template in primarytreatmentforstages Iand IIAwasreinforcedinsubsequentyearswith reaffirmation of the predictable drainage patterns intesticular cancer. In addition, the hypothesis that the drainagefollows that of the testicular veins (on either side) to a so-called“lymphatic epicenter”was refuted [14].

Ultimately, an attempt to achieve sympathetic preserva-tion and antegrade ejaculation has resulted in greater use of

eithermodified templatesornerve-sparingRPLND.The formeris accomplished by staying above the inferior mesentericarteries (based on the distribution of nodal disease referred toabove), whereas a prospective nerve-sparing RPLND involvesidentificationandpreservationofsympatheticnerves fromtheT12–L3 thoracolumbar spinal cord in addition to thehypogastric plexus [15]. Nerve-sparing templates may evenbe applicable to postchemotherapy RPLNDs, whereas modi-fied templates have, historically, been advocated for primarysurgery [16], but its use in the postchemotherapy setting isevolving. Long-term follow-up studies that prove the absenceof late relapse will be needed before suchmodified templatescan be viewed as standard of care, and it seems unlikely thatthe hypothesis would ever be tested in a randomized trial.

INDICATIONS FOR POSTCHEMOTHERAPY RPLND IN

SEMINOMA GERM CELL TUMORS

Postchemotherapy residual masses in patients with advancedseminoma warrant a different approach to that given toresidual masses after chemotherapy in patients with non-seminoma. In general, the chance for malignancy is low if thetumor size is,3 cm and, therefore, observation is warranted.However, it increases to approximately 30% for residualmasses $3 cm [9, 10]. Patients with pure seminoma andresidual tumors .3 cm after chemotherapy should besubmitted for PET CT as described above. If the PET scan ispositive, then biopsy or surgery is indicated. Of importance,seminoma appears to remain sensitive to radiation afterchemotherapy and, therefore, this approach, in addition to

Figure 1. Retroperitoneal lymph node dissection. (A): Aorta. (B):Vena cava. (C): Left renal vein.

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surgery, should be considered [9]. There appears to be anincreased rate of perioperative morbidity after RPLND forseminoma. For reasons that are not clear, the residual massesafter advanced seminoma treated with cisplatin-basedchemotherapy are associated with much more extensivefibrosis and, thus, constitute a much more complex surgicalchallenge. Albeit retrospective, one study evaluating out-comes in patients submitted for RPLND with seminomasuggested a higher rate (38%) of additional operativeprocedures (e.g., nephrectomy, inferior vena cava resection,arterial grafting, or bowel resection) as compared with thoseundergoing the sameprocedure for nonseminoma (26.8%). Asexpected, the rate of postoperative complications was alsogreater in the seminoma group (24.7% vs. 20.3%) [17].

Thereappears tobean increased rateofperioperativemorbidityafterRPLNDforseminoma.For reasonsthatare not clear, the residual masses after advancedseminoma treated with cisplatin-based chemother-apy are associated withmuchmore extensive fibrosisand, thus, constitute a much more complex surgicalchallenge.

INDICATIONS FOR POSTCHEMOTHERAPY RPLND IN

NONSEMINOMA GERM CELL TUMORS

Debate continues regarding which patients should be sub-mitted for PC RPLND, most specifically around subcentimeterresidual masses. Two divergent views are centered on theuncertainty and unpredictability regarding the biologicbehavior of residual microscopic teratoma as well as thepossibility of viable cancer. Furthermore, there remainsvariation among institutions as to what constitutes a radio-graphically normal retroperitoneum. The proponents ofRPLND (Table 1) cite several observations, including a Norwe-gian study demonstrating 33% (29 of 87) of tumors#2 cm ashaving viable germ cell or teratoma, of which 55% (16 of 29)were#1 cm [18]. Furthermore, Carver et al., from MemorialSloan-Kettering Cancer Institute, reported on 532 patientswho underwent RPLND after chemotherapy: 154 patients hadresidual tumors#1cm,ofwhich28%hadeither teratomaand/or viable germ cell (the majority were teratoma) [19]. Onmultivariate analysis, teratoma within the primary specimenas well as relative change in nodal size predicted teratomawithin the retroperitoneum [19].

In contrast, the group from IndianaUniversity (Table 2) hasadvocated surveillance of subcentimeter residual massesbased on review of their experience. In 2009, Ehrlich et al.

reported on 141 patients determined to have a CR afterchemotherapy, defined as normalization of tumor markers aswell as radiographicdisease,1cm[20].Median follow-upwas15.5years, and12 (9%)patients experienced relapse,with four(3%) deaths attributed to germ cell tumor (GCT). Only six sitesof relapse were in the retroperitoneum, suggesting that onehalf of the patients with relapse had the potential to benefitfrom PC RPLND. International Germ Cell Consensus Classifica-tion (IGCCC) predicted outcome with good-risk diseaseenjoying a 99% cause-specific survival versus 73% if diseaseriskwas intermediate to poor. However, only 32 (29%)patientsof theentire cohortwereclassified as intermediate topoor risk[20, 21]. Another retrospective study (Table 2) in support ofsurveillance was reported in 2008, evaluating 276 patientsfromboth theBritish Columbia Cancer Agency and theOregonTestis Cancer Program [22]. Like the series from IndianaUniversity, 161underwent surveillance for CR (same criteria asabove); however, the median follow-up was much shorter(only 40 months), lending uncertainty to the potential forfurther late relapses.Ten patients (6%) relapsed at amedian of52 months, all of whom were salvaged and continuously inremission after amedian follow-up of 64months. Interestingly,all but two of the relapses were considered to have pristinepostchemotherapyscans (i.e.,noradiographic residualdisease),and all but one of the relapses were in the retroperitoneum.Salvage therapy consisted of nine RPLNDs (one after additionalchemotherapy) and one received only systemic chemotherapy.These two surveillance studies illustrate that the most likelyrecurrence site for patients who do not undergo immediatepostchemotherapy RPLND is the retroperitoneum [23].

The German Testicular Group analyzed the pathologicaloutcomes of patients undergoing postchemotherapy RPLNDfor any size tumor [24]. Size correlatedwith potential findings:those with tumors ,1 cm had a 9.4% and 21% chance ofharboring either viable cancer or mature teratoma, respec-tively. These findings elevated to 21% and 25% for post-chemotherapy tumors 1–1.5 cm and, ultimately, to 36% and42%for thosetumorsgreater.1.5cminsize [21,24].Theusualhistologic findings after PC RPLND have been reported as40%–50% fibrosis/necrosis, 35%–40% teratoma, and approx-imately 10% viable germ cell tumor; of importance, a higherproportion of viable cancer was noted in the early series, priorto the implementation of predictive algorithms that matchedaggression of chemotherapy to anticipated prognosis. There-fore, based on the considerations above, one’s ability topredict (to some degree) the histology of a postchemotherapymass is based on the size of the mass after primarychemotherapy [21, 23, 24]. Several groups have evaluatedpredictive models in an attempt to determine retroperitonealpathology [25–29]; unfortunately, all had variable success.

Table 1. Postchemotherapy pathology for patients with residual masses#2 cm and#1 cm

Studyn (£2 cm [18]or <2 cm [19]) T and/or GCT n (£1 cm) T and/or GCT

Norwegian Radium Hospital [18] 87 29 (33%) (23 T; 6 GCT) 54 16 (29%) (11 T; 5 GCT)

Memorial Sloan-Kettering CancerCenter [19]

237 75 (31.6%) (62 T; 11 GC;2 mixed)

154 43 (27.9%) (33 T; 8 GCT;2 mixed)

Abbreviations: GCT, germ cell tumor; T, teratoma.

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It appears that patients who achieve a complete radio-graphic response (normalization of tumor markers andradiographic disease #1 cm) after primary chemotherapyusually do not require postchemotherapy surgery [23]. Ofcourse, these patients must be followed carefully as somewillrequire salvage RPLND and consideration of further chemo-therapy depending on the histologic results. Of note, westrongly advocate review of images by a highly experiencedsurgeon, oncologist, and radiologist to make this determina-tion. Any residual tumor $1 cm in size should be removedbecause of the increasing probability of either viable tumor orteratoma [18, 21, 23, 24].

Finally, historical data have suggested that the morbiditywas asmuchas twofold greater (20.7%) in patients undergoingpostchemotherapy RPLND as compared with primary RPLND[15, 30]. Often this was secondary to pulmonary toxicity (adultrespiratory distress syndrome or prolonged ventilation) frombulky retroperitoneal disease and bleomycin-induced pulmo-nary toxicity. However, current literature suggests that themorbidity afterpostchemotherapyRPLND ismorecomparableto that seen after primary RPLNDwith the exception of greaterblood loss and operative time in addition to a reduced chancetomaintain antegrade ejaculations [31].This shift ismost likelydue to surgical experience, collaboration with other surgicaldisciplines (i.e., aqualifiedandexperiencedvascular surgeon isvital), and improvedchemotherapy thathas resulted in smallerresidual volumes of tumor. All of the above underscores theneed to have this surgery performed at centers with consider-able expertise as well as appropriate ancillary services.

CHEMOTHERAPY AFTER POSTCHEMOTHERAPY RPLNDCurrent treatment paradigms predominantly involve second-line chemotherapy after the finding of viable GCT followingpostchemotherapy surgery (including RPLND and metastasec-tomy). Fizazi et al., in a retrospective analysis, evaluated theoutcomes of 238 patients, all of whom had normal tumormarkers before resection and residual viable NSGCT (so-called“surgical complete response”) removed following initial in-duction chemotherapy [32]. Seventy percent of their cohortreceived various postsurgery (second-line) chemotherapyregimens. Patientswere stratified to oneof three groups basedon three identified risk factors: complete resection, ,10% ofviablemalignantcells, andgood-risk IGCCC.Thosewithall threefactorswere consideredgoodrisk, thosewithoutoneof the riskfactors were considered intermediate risk, and those withouttwo or three were considered poor risk. Patients in thefavorable grouphad a 100%overall survival (OS) rate at 5 yearsirrespective of postoperative chemotherapy. After adjustmentfor tumor volume, risk status, and status of resection,postoperative chemotherapy was associated with a signifi-cantly better progression-free survival (PFS) (p, .001) but not

overall survival [32]. A follow-up validation study wasperformed in 2008 across 12 institutions [33]. Ninety percentof patients underwent first-line chemotherapy with cisplatin.Median follow-upwas 65months and, similar to the first study,5-year PFS for the entire cohort was 65%, with 5-year OS being72%.The indices of complete resection,,10% viable germ celland IGCCC risk status, were together highly predictive of bothPFS (p5 .0008) and OS (p5 .003). However, as with the firststudy, there was no evidence of a survival benefit withpostsurgery chemotherapy; thus, the index above doesprognosticate butdoes not predict response to treatment [33].

This does bring into question the need for second-linechemotherapy in all patients with viable GCT after surgery inthe postchemotherapy setting, especially for those patientswho have undergone complete resection. However, the twostudies above were retrospective, analyzing a cohort amongmultiple institutions and overmany years, thusweakening theinterpretation of the data.We currently consider observationversus several cycles of adjuvant cisplatin-based chemother-apy for those patients with residual viable GCT who havereceived induction chemotherapy only [34], with the durationof chemotherapy predicated on apparent response andtoxicity; however, we favor the concept that this would bea fertile area for a multicenter collaborative trial to identifya truly optimal approach.

POSTCHEMOTHERAPY SURGERY FOR SITES OUTSIDE

THE RETROPERITONEUM

Theconcordancebetween retroperitonealmasses andmassesoutside the retroperitoneum is incomplete, with outcomesdictated by the ability to resect all residual masses in additionto tumor marker status and whether viable GCT remains. Infact, the histologic discordance between sites is reported to bebetween 25%and 47% [35, 36]. Interestingly, the concordancebetweenpatientswithbilateral residual lungmasseswhohavepure necrosis in the first lung appears very good, with 19 of 20(95%) also having this finding in the second lung [37].Therefore, careful consideration to observation regardingacontralateral lungmassafter the findingofnecrosis in the firstcan be given; however, this does not hold true for mediastinalmasses. Our view is that, in general, all masses should beconsidered for simultaneous resection if technically feasible.

The use of surgery for either relapse or in the primarysetting in patientswithmetastatic germcell tumor to thebrainremains a topic of debate. Prospective trials are lacking andalmost certainly will not be conducted as this constitutes lessthan 10% of patients with advanced germ cell tumors and lessthan 1% of all germ cell tumor patients [38]. NationalComprehensive Cancer Network guidelines recommendradiation for patients with brain metastasis following chemo-therapy, with surgery reserved for consideration in those in

Table2. Outcomeofsurveillance forpatientswithcomplete response (#1 retroperitonealmass; normalized tumormarkers)after

first-line chemotherapy

Study Patients, n Median follow-up (yr) Relapse Relapse in retroperitoneum

Oregon/British Columbia Cancer Agency [22] 161 3.3 10 (6%) 9 (5.6%)

Indiana [20] 141 15.5 12 (9%) 6 (4.3%)



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whom it appears feasible (solitary metastasis) [39]. However,the evidence basis for this recommendation is not particularlystrong. In the presence of significant elements of choriocar-cinoma (predicted by the histology of the primary tumor or ofmetastases at other sites or very high circulating humanchorionic gonadotropin), we believe that initial surgicalresectionof isolatedbrainmetastasesmaybe safer (if feasible)to avoid life-threatening intracranial hemorrhage afterchemotherapy or radiotherapy.

Bone metastasis is also rare, constituting less than 1% ofmetastasis at the time of primary diagnosis or relapse [40].However, it has been shown in patients specifically with poor-risk disease to constitute up to 9% [41]. In this study, Oechsleetal. retrospectivelyreviewed40patientswithbonemetastasesfrom a cohort of 434 patients with poor-risk disease [41]. Allpatients underwent primary high-dose cisplatin-based che-motherapy with peripheral blood stem cell reinfusion. Fourpatients (10%) underwent surgical consolidation, all of whomhad the finding of necrosis at the time of surgery [41]. As withdisease of the brain, the ultimate timing and role of surgery forbone metastasis remain uncertain.

EXTRAGONADAL GERM CELL TUMORS

Extragonadal germ cell tumors represent less than 5% of alladult germ cell malignancies. Most of these are located in theanterior mediastinum followed by the retroperitoneum andvery rarely in the pineal gland or presacral area [42]. Thosecontaining seminoma are considered good or intermediateIGCCC risk and are recommended to undergo chemotherapy,usually with very good outcomes irrespective of location.Unfortunately, primary mediastinal nonseminomatous germcell tumors (PMNSGCTs) are considered IGCCC poor risk andcarry only a 40%–50% rate of survival after combinationtreatment with cisplatin-based chemotherapy and surgery[42, 43]. This is inferior to those occurring in the retroper-itoneum, which are considered IGCCC good or intermediateclassificationdependingon tumormarker status. Surgeryplaysa vital role in the management of PMNSGCTs as there is a highrate of viable tumor at the time of resection after chemother-apy [44, 45]. In general, we advocate that patients withPMNSGCTs are treated initially with VP-16, etopside orvinblastine plus ifosfamide and cisplatin, or another poor-riskcisplatin-based regimen (to avoid bleomycin and its potentialpulmonary toxicity) followed by thoracotomy and resection(residual mass is usually present). It is important that thiscomplex surgery is undertaken by an experienced thoracicsurgeon who has done this type of surgery, assuming thedisease is deemed potentially resectable [45]. Because of thelack of effective salvage therapy, resection should beconsidered even in the face of elevated tumormarkers as wellas at the time of any recurrence [42, 45].

SURGERYAFTER SALVAGE OR SECOND-LINE CHEMOTHERAPY

It should be mentioned that the paradigm for aggressivesurgical resectionafter salvageorsecond-line chemotherapy isto some degree different. In general, these are patients whoprogressed after first-line chemotherapy or who remain withunresectable disease. Residual masses after second-linechemotherapy have been associated with a much higherchanceof residualGCT [10,35], andsurgery isoftenconsidered

even in the faceofelevatedtumormarkerstatusbecauseof thepaucity of effective, alternative options.

However, Eggener et al., in a review of 71 patients aftermultiple chemotherapy regimens in 2007 (90% receivedsecond-line chemotherapy only), suggested that there wasdeclining incidence of viable GCT in the retroperitonealresidual mass (ultimately paralleling that seen after primarychemotherapy) [46]. Overall, the rate of viable GCT was 28%;however, when analyzing the subset of patients who receivedtaxane therapy, this rate dropped from 42% to 14%. Finally,with this reduction came higher rates of fibrosis (63% vs. 39%)with a relatively stable distribution of teratoma (31% vs. 33%).Of note, the rate of viableGCTor teratoma if locatedoutside ofthe retroperitoneum was 31%. The 10-year disease-specificsurvival (DSS) was 70%, but was most favorable for those witha finding of only fibrosis (87%), as compared with teratoma(47%)or viableGCT (47%).Onmultivariate analysis, tumor size$5 cm aswell as the presence of GCTpredictedDSS [46]. All ofthe above supports the vital roleof postchemotherapy surgeryafter second-line chemotherapy while at the same timesuggesting that second-line taxane (paclitaxel, ifosfamide, andcisplatin or paclitaxel and ifosfamide followed by carboplatinand etoposide plus peripheral blood stem) therapy hasimproved the outcome and shifted histopathological distribu-tionsimilar to that seenafter first-lineplatinum-basedtherapy.

TEMPLATE

Controversy regarding the anatomical extent of RPLND afterchemotherapycontinues. Patients in the 1970s and1980softenhad high-volume residual disease necessitating full bilateralretroperitoneal dissection including suprahilar dissection.However, current chemotherapy regimens tend to leaveremainingdiseaseburdenvery lowandrestrictedtotheprimarylanding zones with contralateral crossover currently less likely[21, 47]. Some have advocated use of intraoperative frozensections to guide extent of surgery. Herr et al. evaluated 62patients, ofwhom37underwent limited lymphnodedissectionbased on the finding of necrosis on frozen section [48]. Theremaining patients underwent bilateral full template dissectionof the retroperitoneum after frozen section revealed viablegerm cell or teratoma. Fourteen patients had relapse, of whomonly 1 had germ cell or teratoma in the retroperitoneum afterlimited dissection. Interestingly, there were six surgicalcomplications, five of which occurred after bilateral dissection[48]. Others have suggested that a template RPLND isappropriate in those patients presenting with low-volumeretroperitoneum disease (,5cm, stage IIA or IIB). Beck et al.evaluated100patients submitted formodified templateRPLND(for postchemotherapy residual disease) after primary chemo-therapy, of which there were only four recurrences in theretroperitoneum after 32 months of follow-up [47]. Interest-ingly, the locations of all recurrences were deemed to also beoutside theboundariesofa full bilateraldissection. In this highlyselect population (98% had good-risk disease and 94% werestage IIA or B), a modified template did not appear to affectoutcome [47].

Another 152 patients with postchemotherapy residualmasses were retrospectively reviewed by Heidenreich et al.from two tertiary referral centers, of whom 98 underwentmodified template resection if the mass was located in the



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primary landing zone and,5 cm [49]. Mean length of surgerywas significantly longer (90minutes) in the full bilateral groupascompared with the modified group. Antegrade ejaculation waspreserved in 85% of patients undergoing modified template(averagemass size of 4.5 cm) but only 25% in those undergoingfull bilateral dissection (averagemass size 11 cm). For the entireanalyzed cohort, there were nine recurrences (three aftermodified dissection [3%] and six after full template dissection[12%]),with only one recurrenceoccurringwithin the boundaryof a modified template dissection and all others occurringoutside the boundaries of a full template dissection. In-terestingly, all recurrences within the modified group wereoutside of the retroperitoneum; however, three in the fullbilateral groupwere suprahilar in location [49].Obviously, thereis some selection bias with the average size for patientsundergoingmodified templatebeing4.5cmversus11cmfor fullbilateral dissection. Also, 30% and 15% were IGCCC poor-riskclassification for the full andmodified groups, respectively [49].

What we take away from this, in contrast to earlier series[50], is that patients with postchemotherapy residual massesneed to be carefully considered for a surgical plan. Also, withthe advancement of systemic therapy, the current tumorburden of residual disease does not parallel that seen 20 yearsago and, thus, the primary landing zones are more likely to bethe only site of disease.Therefore, in patients with stage IIB orlower with a postchemotherapy residual mass within theprimaryknownlandingsite,thesurgeoncanconsider templatedissection. High-volume tumors (i.e., stage IIC) and those witheither pre- or postchemotherapy masses outside of thepredicted lymphatic drainage should be submitted for fullbilateral template as well as consideration for suprahilar andiliac dissection. Ultimately, however, there is little substitutefor surgeon experience and judgment; therefore, we find thisto be paramount in deciding the extent of dissection. It shouldalso be emphasized that this type of surgery should not beundertaken solo by a surgeon who is inexperienced in thenuances of postchemotherapy germ cell cancer surgery.

LAPAROSCOPYThe use of laparoscopy in postchemotherapy RPLND appearstechnically feasible but uncertainwith regards to its long-termoutcome [51, 52]. Most of the current experience is in theprimary setting as opposed to after chemotherapy. In general,the total lymph nodes removed in series evaluating laparo-scopic RPLNDhavebeen considerably less than those reportedforopenseries [53–55].Understandingtheutmost importanceof “controlling the retroperitoneum,” we have not advocatedlaparoscopy in the postchemotherapy setting. Currently, thegold standard for postchemotherapy RPLND remains an opensurgical approach.

“REDO” RPLNDAs mentioned above, it is of utmost importance to achievecomplete resection at the time of initial surgery. Hendry et al.reported on 442 patients undergoing RPLND for radiographicmasses$1 cm, ofwhom112 received their surgery in a salvagefashion [56]. The salvage group consisted of a referredpopulation who had recurrent disease after observation ofa known para-aortic mass. Also, they were submitted forreinduction chemotherapyprior to surgery. Complete resection

wasaccomplishedin87%oftheprimarygroupversus72%ofthesalvagegroup, and lackofcomplete resectionwaselucidatedonmultivariate analysis as a predictor for OS. The need forconcurrent nephrectomy was statistically twice as high in thesalvage group, with an operative mortality 1.8% as comparedwith 0.9% in the primary group. Finally, overall survival wasimprovedbyan absolute differenceof 33% in theprimary (89%)as compared with the salvage (56%) group [56]. Incompletecontrol of the retroperitoneum after primary RPLND has beenshown by others to be associated with an increased complica-tion rate as compared with primary RPLND [57]. This at timesrequires coordination from additional surgical subspecialties(e.g., vascular surgery). McKernion et al. evaluated 34 patientswho underwent primary PC RPLND who subsequently weresubmitted for reoperation [58]. Teratoma was the mostcommon histologic finding at PC RPLND and at the time ofreoperation.Notably, at amedian follow-upof 29.5months, thedisease-specific survival rate for patients undergoing a secondRPLND following PC RPLND was 56% [58]. Sonneveld et al.evaluated 51 patients with residual teratoma after postchemo-therapy RPLND, of whom 15.7% (8) were deemed by thesurgeon to be “incomplete” resections. Of these 8 patients, 4relapsedwith disease in the retroperitoneum, emphasizing theimportance of complete resection [59]. Another more recentstudyevaluated theoutcomesof 18patientsundergoing repeatRPLND, of whom 3 (16.7%) were deemed “out-of-field”recurrence, leaving the remaining83%as“in-field” recurrences.Most recurrences were located in the interaortocaval, para-aortic, and suprahilar locations, with 10 patients (63%) havingresidual teratoma or GCT. Adjunctive procedures such asthoracotomy or vessel resection and grafting were required55%ofthetime,andtheoverallpostoperativecomplicationratewas 38.8% [57]. This increased rate of perioperative complica-tions as well as location of recurrence have been supported byothers [58,60].The locationoftherecurrencesmayberelatedtoincomplete surgery with respect to the renoaortic junction andthe need to control (and dissect) all major tributaries beforeaddressing any retroperitoneal mass. Of note, patients withteratomaafterprimaryorpostchemotherapyRPLNDoftenhaveteratomaon repeat RPLND (as evidencedby12 of 15patients inone series [58]).

Our own experience and review of the above literature giveus some insight into how toapproach those patients presentingwith residual masses in the retroperitoneum after primaryRPLND who are also marker-negative. First, patients with theappearance of teratoma on imaging (cystic masses) would bebest servedwithupfront repeat surgery.Teratomaonlyon initialRPLND (whether it be primary or after chemotherapy) oftenpredicts teratoma in the residual retroperitoneum mass, andthese patients also should be submitted for repeat surgery. It isreasonable to use percutaneous biopsy to attempt to identifypatients who may have only necrosis/fibrosis. This would bemost appropriate in those patients with negative tumormarkers, no teratomatouselementsat the timeof initialRPLND,and no radiographic features suggesting teratoma. It is quiteevident that salvage chemotherapy cannot salvage inadequatesurgical resection, and complete surgical resection of anyresidualmasses is imperative, as thismaybetheonly prognosticfactor that we can actually control. Moreover, it is obvious that



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these complex surgeries need to be planned and coordinatedappropriately to optimize surgical outcomes and success.

It is quite evident that salvage chemotherapy cannotsalvage inadequate surgical resection, and completesurgical resection of any residual masses is impera-tive, as this may be the only prognostic factor that wecanactually control.Moreover, it is obvious that thesecomplex surgeries need to be planned and coordi-nated appropriately to optimize surgical outcomesand success.

“DESPERATION” POSTCHEMOTHERAPY RPLNDTheuse of “desperation”PCRPLNDhas been coined to refer tothe use of surgery in patients with increased serum tumormarkers after chemotherapy [21, 61]. At the time ofdesperation surgery, the incidence of viable GCT ranges from40% to 81%, considerably higher than that seen after first-linechemotherapy and normalized tumormarkers [61]. Beck et al.reported on 114 patients withmetastatic germ cell tumor andelevated tumor markers after first- or second-line chemother-apy [62]. Retroperitoneal pathology was GCT in 53.5% (28%after first-line chemotherapy; 75.8% after second-line chemo-therapy), teratoma in 34.2%, and fibrosis in 12.3%. There wasa54%5-yearoverall survival for theentirecohort. Predictorsofadverseoutcomes in the inductiongroupwere retroperitonealhistology (finding of cancer was least favorable), whereasincreasing beta-human chorionic gonadotropin, elevatedalpha-feto protein (continuous variable), redo RPLND, andGCT histology predicted adverse outcome in the salvagechemotherapy group [62]. Literature review on the concept ofdesperation RPLND suggests that results are more favorableamong those with stable or declining tumor markers asopposed to elevated ones. Also, in general, 50% of patientswith elevated tumor markers at the time of surgery will havemature teratoma or fibrosis/necrosis, with a long-termdisease-free interval in one third of patients with viable GCT[61–63]. It should be underscored that the use of RPLND in theface of rising tumormarkers and the appearance of resectabledisease constitutes an infrequent clinical condition. Generalguidelines for considering surgery include declining or plateau

serum tumor markers after chemotherapy, slowly increasingtumor markers after an initial complete response to chemo-therapy (primaryor secondary), resectabledisease (one to twosites), increasing markers, and apparently resectable diseaseafter all systemic options have been used [62].

CONCLUSIONImprovement in systemic therapy has, to a large degree, nowrelegated surgery for advancedGCTs to thepostchemotherapysetting. Its use within the armamentarium for treatment ofadvanced GCTs remains vital.We have learned much over thepast several decades. Masses outside the retroperitoneumshould be completely resected with the possible exception ofbilateral residual lungmasses when resection of the first massshows necrosis. For seminoma, postchemotherapy RPLND orbiopsy and radiation should be considered for masses.3 cmthat are also PET-positive. For NSCGT, postchemotherapyRPLND should be performed for tumors $1 cm and normalmarkers, thosewith plateauing tumormarkers, and thosewithresidual in-field masses and negative markers after priorRPLND. Additional indications include normal markers orplateauing markers after salvage chemotherapy, and in thedesperation setting if the tumor appears resectable. It remainsvitally important to “control the retroperitoneum” by re-section of all disease the first time, thus avoiding the potentialdisturbing consequences associated with redo RPLND. Al-though our understanding regarding its use has evolved, itremains a complex procedurewith the potential for significantcomplications; therefore, it is paramount to consider referralto facilities with this expertise.

AUTHOR CONTRIBUTIONSConception/design: Stephen B. Riggs, Earl F. Burgess, Kris E. Gaston, DerekRaghavan

Provision of study material or patients: Stephen B. RiggsCollection and/or assembly of data: Stephen B. Riggs, Caroline A. MerwarthManuscript writing: Stephen B. Riggs, Derek RaghavanFinal approval of manuscript: Stephen B. Riggs, Earl F. Burgess, Kris E. Gaston,Caroline A. Merwarth, Derek Raghavan

DISCLOSURES

DerekRaghavan: Sanofi Aventis (C/A).The other authors indicatednofinancial relationships.(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert

testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/

inventor/patent holder; (SAB) Scientific advisory board

REFERENCES

1. Hong WK, Wittes RE, Hajdu ST et al. Theevolution of mature teratoma from malignanttesticular tumors. Cancer 1977;40:2987–2992.

2. Reddel RR, Thompson JF, Raghavan D et al.Surgery in patients with advanced germ cellmalignancy following a clinical partial response tochemotherapy. J Surg Oncol 1983;23:223–227.

3. Donohue JP, Einhorn LH, Williams SD. Cytor-eductive surgery for metastatic testis cancer:Considerations of timing and extent. J Urol 1980;123:876–880.

4. Hendry WF, Goldstraw P, Husband JE et al.Elective delayed excision of bulky para-aortic lymphnode metastases in advanced non-seminomagerm cell tumours of testis. Br J Urol 1981;53:648–653.

5.Vugrin D, Whitmore WF Jr., Sogani PC et al.Combined chemotherapy and surgery in treatmentof advanced germ-cell tumors. Cancer 1981;47:2228–2231.

6. Becherer A. PET in testicular cancer. MethodsMol Biol 2011;727:225–241.

7. De Santis M, Becherer A, Bokemeyer C et al. 2-18fluoro-deoxy-D-glucose positron emission to-mography is a reliable predictor for viable tumor inpostchemotherapy seminoma: An update of theprospective multicentric SEMPET trial. J Clin Oncol2004;22:1034–1039.

8.Motzer R, Bosl G, Heelan R et al. Residual mass:An indication for further therapy in patients withadvanced seminoma following systemic chemo-therapy. J Clin Oncol 1987;5:1064–1070.

9. Puc HS, Heelan R, Mazumdar M et al. Manage-ment of residual mass in advanced seminoma:Results and recommendations from the MemorialSloan-KetteringCancer Center. J ClinOncol 1996;14:454–460.

10. Herr HW, Sheinfeld J, Puc HS et al. Surgery fora post-chemotherapy residual mass in seminoma. JUrol 1997;157:860–862.

11. BechererA, DeSantisM, KaranikasGet al. FDGPET is superior to CT in the prediction of viabletumour in post-chemotherapy seminoma residuals.Eur J Radiol 2005;54:284–288.

12. Donohue JP, Zachary JM, Maynard BR.Distribution of nodal metastases in nonsemi-nomatous testis cancer. J Urol 1982;128:315–320.



CME



Dow

nloaded from


13. Ehrlich Y, Yossepowitch O, Kedar D et al.Distribution of nodal metastases after chemother-apy in nonseminomatous testis cancer: A possibleindication for limited dissection. BJU Int 2006;97:1221–1224.

14.Weissbach L, Boedefeld EA. Localization ofsolitary and multiple metastases in stage II non-seminomatous testis tumor as basis for a modifiedstaging lymphnodedissection in stage I. J Urol 1987;138:77–82.

15.Tarin T, Carver B, Sheinfeld J. The role oflymphadenectomyfor testicularcancer: Indications,controversies, and complications. Urol Clin NorthAm 2011;38:439–449, vi [vi.].

16. Pettus JA, Carver BS, Masterson T et al.Preservation of ejaculation in patients undergoingnerve-sparing postchemotherapy retroperitoneallymph node dissection for metastatic testicularcancer. Urology 2009;73:328–331; discussion331–322.

17.Mosharafa AA, Foster RS, Leibovich BC et al. Ispost-chemotherapy resection of seminomatouselements associated with higher acute morbidity?J Urol 2003;169:2126–2128.

18. Oldenburg J, Alfsen GC, Lien HH et al. Post-chemotherapy retroperitoneal surgery remainsnecessary in patients with nonseminomatous tes-ticular cancer andminimal residual tumormasses. JClin Oncol 2003;21:3310–3317.

19. Carver BS, Bianco FJ Jr., Shayegan B et al.Predicting teratoma in the retroperitoneum in menundergoing post-chemotherapy retroperitoneallymph node dissection. J Urol 2006;176:100–103;discussion 103–104.

20. Ehrlich Y, BramesMJ, Beck SDet al. Long-termfollow-up of cisplatin combination chemotherapyin patients with disseminated nonseminomatousgerm cell tumors: Is a postchemotherapy retro-peritoneal lymph node dissection needed aftercomplete remission? J Clin Oncol 2010;28:531–536.

21. Heidenreich A, Pfister D. Retroperitoneallymphadenectomy and resection for testicularcancer: An update on best practice. Ther Adv Urol2012;4:187–205.

22. Kollmannsberger C, Daneshmand S, So A et al.Management of disseminated nonseminomatousgerm cell tumors with risk-based chemotherapyfollowed by response-guided postchemotherapysurgery. J Clin Oncol 2010;28:537–542.

23. Osanto S, Richie J. Testicular cancer. In:International Consultation on Testicular Cancer.Shanghai, China: Societe Internationale d’Urologie.2011:112–117.

24. Pfister D, Busch J, Winter C et al. Pathohisto-logical findings in patients with nonseminomatousgerm cell tumors (NSGCT) who undergo postche-motherapy retroperitoneal lymph node dissection(PC-RPLND) for small tumours. J Clin Oncol 2011;29(suppl 7):244a.

25. Debono DJ, Heilman DK, Einhorn LH et al.Decision analysis for avoiding postchemotherapysurgery in patients with disseminated nonsemi-nomatous germ cell tumors. J Clin Oncol 1997;15:1455–1464.

26. Donohue JP, Rowland RG, Kopecky K et al.Correlation of computerized tomographic changesandhistological findings in80patientshavingradicalretroperitoneal lymph node dissection after che-motherapy for testis cancer. J Urol 1987;137:1176–1179.

27.Vergouwe Y, Steyerberg EW, Foster RS et al.Validation of a prediction model and its predictorsfor the histology of residual masses in nonsemi-nomatous testicular cancer. J Urol 2001;165:84–88;discussion 88.

28. Albers P,Weissbach L, Krege S et al. Predictionof necrosis after chemotherapy of advanced germcell tumors: Results of a prospective multicentertrial of the German Testicular Cancer Study Group. JUrol 2004;171:1835–1838.

29. Steyerberg EW, Keizer HJ, Fossa SD et al.Prediction of residual retroperitoneal mass histol-ogy after chemotherapy for metastatic nonsemi-nomatous germ cell tumor: Multivariate analysis ofindividual patient data from six study groups. J ClinOncol 1995;13:1177–1187.

30. Baniel J, Foster RS, Rowland RG et al. Compli-cations of post-chemotherapy retroperitoneallymph node dissection. J Urol 1995;153:976–980.

31. Subramanian VS, Nguyen CT, Stephenson AJet al. Complications of open primary and post-chemotherapy retroperitoneal lymph node dissec-tion for testicular cancer. Urol Oncol 2010;28:504–509.

32. Fizazi K, Tjulandin S, Salvioni R et al. Viablemalignant cells after primary chemotherapy fordisseminated nonseminomatous germ cell tumors:Prognostic factors and role of postsurgery chemo-therapy—Results from an international studygroup. J Clin Oncol 2001;19:2647–2657.

33. Fizazi K, Oldenburg J, Dunant A et al. Assess-ing prognosis and optimizing treatment inpatients with postchemotherapy viable nonsemi-nomatous germ-cell tumors (NSGCT): Results ofthe sCR2 international study. Ann Oncol 2008;19:259–264.

34. Fox EP, Weathers TD, Williams SD et al. Out-come analysis for patients with persistent non-teratomatousgermcell tumor inpostchemotherapyretroperitoneal lymphnodedissections. J ClinOncol1993;11:1294–1299.

35. Hartmann JT, Schmoll HJ, Kuczyk MA et al.Postchemotherapy resections of residual massesfrommetastatic non-seminomatous testicular germcell tumors. Ann Oncol 1997;8:531–538.

36. Brenner PC, Herr HW, Morse MJ et al. Simul-taneous retroperitoneal, thoracic, and cervicalresection of postchemotherapy residual masses inpatients with metastatic nonseminomatous germcell tumors of the testis. J Clin Oncol 1996;14:1765–1769.

37. Besse B, Grunenwald D, Flechon A et al.Nonseminomatous germ cell tumors: Assessingthe need for postchemotherapy contralateral pul-monary resection in patients with ipsilateral com-plete necrosis. J Thorac Cardiovasc Surg 2009;137:448–452.

38. Oechsle K, Bokemeyer C. Treatment of brainmetastases from germ cell tumors. Hematol OncolClin North Am 2011;25:605–613, ix [ix.].

39. NCCN Clinical Practice Guidelines in Oncology.Testicular Cancer. Version 1, 2011. Available athttp://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed January 4, 2014.

40. Jamal-Hanjani M, Karpathakis A, Kwan A et al.Bone metastases in germ cell tumours: Lessonslearnt froma large retrospective study.BJU Int 2013;112:176–181.

41. Oechsle K, Bokemeyer C, Kollmannsberger Cet al. Bonemetastases in germ cell tumor patients. JCancer Res Clin Oncol 2012;138:947–952.

42. Albany C, Einhorn LH. Extragonadal germ celltumors: Clinical presentation and management.Curr Opin Oncol 2013;25:261–265.

43. Bokemeyer C, Nichols CR, Droz JP et al.Extragonadal germ cell tumors of the mediastinumand retroperitoneum: Results froman internationalanalysis. J Clin Oncol 2002;20:1864–1873.

44.Vuky J, Bains M, Bacik J et al. Role ofpostchemotherapy adjunctive surgery in the man-agement of patients with nonseminoma arisingfrom the mediastinum. J Clin Oncol 2001;19:682–688.

45. Kesler KA, Rieger KM, Hammoud ZT et al. A25-year single institution experience with sur-gery for primary mediastinal nonseminomatousgerm cell tumors. Ann Thorac Surg 2008;85:371–378.

46. Eggener SE, Carver BS, Loeb S et al. Pathologicfindings and clinical outcome of patients undergo-ing retroperitoneal lymph node dissection aftermultiple chemotherapy regimens for metastatictesticular germ cell tumors. Cancer 2007;109:528–535.

47. Beck SD, Foster RS, Bihrle Ret al. Is full bilateralretroperitoneal lymph node dissection alwaysnecessary for postchemotherapy residual tumor?Cancer 2007;110:1235–1240.

48. Herr HW. Does necrosis on frozen-sectionanalysis of a mass after chemotherapy justifya limited retroperitoneal resection in patientswithadvanced testis cancer? Br J Urol 1997;80:653–657.

49. Heidenreich A, Pfister D, Witthuhn R et al.Postchemotherapy retroperitoneal lymph nodedissection in advanced testicular cancer: Radical ormodified template resection. Eur Urol 2009;55:217–224.

50.Wood DP Jr., Herr HW, Heller G et al. Distribu-tion of retroperitoneal metastases after chemo-therapy in patients with nonseminomatous germcell tumors. J Urol 1992;148:1812–1815; discussion1815–1816.

51. Steiner H, Zangerl F, Stohr B et al. Results ofbilateral nerve sparing laparoscopic retroperito-neal lymph node dissection for testicular cancer. JUrol 2008;180:1348–1352; discussion 1352–1343.

52. Kimura Y, Nakamura T, Kawauchi A et al. Post-chemotherapy nerve-sparing laparoscopic retro-peritoneal lymph node dissection in stage IIBtesticular cancer. Int J Urol 2013;20:837–841.

53.Thompson RH, Carver BS, Bosl GJ et al.Contemporary lymph node counts during primaryretroperitoneal lymph node dissection. Urology2011;77:368–372.

54.Thompson RH, Carver BS, Bosl GJ et al.Evaluation of lymph node counts in primaryretroperitoneal lymph node dissection. Cancer2010;116:5243–5250.

55. Rassweiler JJ, Scheitlin W, Heidenreich A et al.Laparoscopic retroperitoneal lymph node dissec-tion: Does it still have a role in the management ofclinical stage I nonseminomatous testis cancer? AEuropean perspective. Eur Urol 2008;54:1004–1015.

56. Hendry WF, Norman AR, Dearnaley DP et al.Metastatic nonseminomatous germ cell tumors ofthe testis: Results of elective and salvage surgery forpatients with residual retroperitoneal masses.Cancer 2002;94:1668–1676.

57. Heidenreich A, Ohlmann C, Hegele A et al.Repeat retroperitoneal lymphadenectomy in



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http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

http://www.nccn.org/professionals/physician_gls/f_guidelines.asp



advanced testicular cancer. Eur Urol 2005;47:64–71.

58.McKiernan JM, Motzer RJ, Bajorin DF et al.Reoperative retroperitoneal surgery for nonsemi-nomatous germ cell tumor: Clinical presentation,patterns of recurrence, andoutcome.Urology2003;62:732–736.

59. Sonneveld DJ, Sleijfer DT, Koops HS et al.Mature teratoma identified after postchemother-apy surgery in patients with disseminated

nonseminomatous testicular germ cell tumors: Aplea for an aggressive surgical approach. Cancer1998;82:1343–1351.

60. Sexton WJ, Wood CG, Kim R et al. Repeatretroperitoneal lymph node dissection formetastatic testis cancer. J Urol 2003;169:1353–1356.

61. Beck SD, Foster RS, Bihrle R et al. Pathologicfindings and therapeutic outcome of desperationpost-chemotherapy retroperitoneal lymph node

dissection in advanced germ cell cancer. Urol Oncol2005;23:423–430.

62. Beck SD, Foster RS, Bihrle R et al. Outcomeanalysis for patients with elevated serum tumormarkers at postchemotherapy retroperitoneallymph node dissection. J Clin Oncol 2005;23:6149–6156.

63. Daneshmand S, Albers P, Fossa SD et al.Contemporary management of postchemotherapytestis cancer. Eur Urol 2012;62:867–876.

CME This article is available for continuing medical education credit at CME.TheOncologist.com.

EDITOR’S NOTE: For further reading on germ cell tumors, watch for the forthcoming commentary by Sara J. Stoneham et al.,“Adolescents and Young Adults with a “Rare” Cancer: Getting Past Semantics to Optimal Care for Patients with Germ CellTumors.”

Germ cell tumors are the third most common cancer diagnosis in adolescent and young adult (AYA) patients aged 15–24.Many cancers that arise in AYA patients, including germ cell tumors, are defined as “rare” because they are relativelyinfrequent during early childhood and older adulthood. Consequently, the clinical care, clinical trials, and biological studyof these cancers have not progressed synchronously with common childhood or adult cancers and gains in overall survivalfor this age group are only half those in either younger or older patients. The authors reflect on how to address this lack ofprogress, usingas their lens, theirownexperience increatingan international, cross-discipline remodelingof theclinical trialdevelopment of GCT to overcome the barriers created by the structure of conventional medical practice.

Forthcoming in the July 2014 issue.



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