SALVAGE SURGERY FOR BULKY LOCAL RECURRENCE OF PROSTATECANCER FOLLOWING RADICAL PROSTATECTOMY

DAN LEIBOVICI,* LANCE PAGLIARO, CHARLES J. ROSSER AND LOUIS L. PISTERS†,‡From the Departments of Urology and Genitourinary Medical Oncology (LP), University of Texas M. D. Anderson Cancer Center,

Houston, Texas

ABSTRACT

Purpose: We report our experience with salvage radical surgery as palliative treatment inpatients with bulky recurrence of prostate cancer following radical prostatectomy (RP).Materials and Methods: From files at the department of urology we identified 5 patients who

had biopsy confirmed, bulky recurrence of prostate cancer after initial RP and subsequentsalvage radiation therapy (4), prior to presentation at our cancer center. Positive surgicalmargins were present in all 5 patients. All received androgen ablation and 4 also receivedsystemic chemotherapy. Due to persistent bulky tumors in the 5 patients and debilitatingunrelenting symptoms, including refractory hematuria, obstructive uropathy and pelvic pain in4, salvage radical surgery was performed. Total pelvic exenteration was done in 4 patients andwide tumor resection with continent urinary diversion was done in 1.Results: Four patients were permanently relieved of local symptoms following surgery and

another had entero-urethral fistula formation. Revision of a continent urinary diversion wasnecessary in another patient who was otherwise free of cancer and of local pelvic symptoms.Long-term symptom-free survival was achieved in 2 patients following surgery at 26 and 56months, respectively. One patient died of metastatic disease 3.5 months after surgery but he hadbeen rendered free of local symptoms by surgery. The other 2 patients are currently free of localsymptoms 5 and 7 months following surgery, respectively. Wound infection, delirium and pro-longed ileus occurred in 1 patient each. Otherwise surgery was well tolerated.Conclusions: Salvage radical surgery is feasible and it provides effective palliation in patients

with bulky local recurrence following RP.KEY WORDS: prostate, prostatic neoplasms, prostatectomy, salvage therapy, radiation therapy, pelvic exenteration,

palliation, radiotherapy

Although radical prostatectomy (RP) consists of completeremoval of the prostate and seminal vesicles encompassingall malignant tissue, there is a risk of recurrent disease,especially with high Gleason scores and when there are pos-itive surgical margins.1–3 Patients with local tumor recur-rence following RP are at an increased risk for progression tometastasis and, in addition, they are prone to severe symp-toms, including hematuria, urinary frequency, incontinence,pelvic pain, bladder outlet obstruction and obstructive renalfailure. Such symptoms can significantly affect patienthealth and general well-being for an extended period.Salvage treatment options for local recurrence of prostate

cancer following RP include androgen ablation and irradia-tion. Although it is well tolerated by most patients, androgenablation is not curative and its ability to control localizedsymptoms is of limited duration. Conversely salvage radia-tion therapy performed in the presence of a low tumor burdencan be curative and provide effective local control.4, 5 How-ever, radiation may induce local symptoms of chronic cystitisor proctitis as well as an increased risk of urinary inconti-nence in patients who have previously undergone RP.6 When

salvage radiation therapy fails to achieve cure, most patientseventually experience systemic progression with poor out-come. However, local control and palliation remain funda-mental needs. In this study we describe the feasibility andefficacy of salvage radical surgery for bulky local recurrenceof prostate cancer following previous RP.

MATERIALS AND METHODS

From the patient files at the department of urology weidentified 5 patients who presented to our cancer centerbetween 1999 and 2004 for the treatment of local recurrenceof prostate cancer following RP and salvage treatments per-formed elsewhere. All patients had positive surgical marginsand negative lymph nodes, and 2 had seminal vesicle involve-ment. Due to prostate specific antigen (PSA) progressionfollowing RP all patients were started on androgen ablation,4 were treated with external beam (EB) radiation therapy (60to 65 cGy) and 1 of them also received brachytherapy. Atpresentation to our institution 4 patients had androgen in-dependent prostate cancer and they were given systemicchemotherapy. Prior to proceeding with salvage surgery allpatients underwent pelvic examination under anesthesia. Afixed mass adherent to the pelvic sidewall was considered acriterion of inoperability.Total pelvic exenteration with fecal and urinary diversion

was performed in 4 patients. The other patient underwent enbloc resection of the tumor with vesicourethral anastomosis,bladder neck closure and creation of a continent urinarydiversion. Outcome end points were local symptom control,biochemical progression-free survival and disease specificsurvival measured from the time of salvage surgery.

Submitted for publication May 6, 2004.Supported by Cancer Center Core Grant CA16672 from the Na-

tional Cancer Institute and a grant from the American Foundation ofUrologic Disease.* Recipient of Fellowship from the American Physician Fellowship

Organization in Israel.† Correspondence and requests for reprints: Department of Urology,

University of Texas M. D. Anderson Cancer Center, 1515 HolcombeBlvd., Unit 446, Houston, Texas 77030 (telephone: 713-792-3250; FAX:713-794-4824; e-mail: lpisters@mdanderson.org).‡ Financial interest and/or other relationship with Abbott.

0022-5347/05/1733-0781/0 Vol. 173, 781–783, March 2005THE JOURNAL OF UROLOGY® Printed in U.S.A.Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000152394.32858.14

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RESULTS

Table 1 lists the clinical and pathological characteristics ofthe study subjects. The time between initial RP and salvagesurgery in the 5 patients was 1.9, 6.2, 7.8, 8.9 and 13.4 years,respectively.Local symptoms disappeared in 4 patients after surgery

and did not recur during followup. In another patientsurgery did not achieve effective palliation and an entero-urethral fistula developed 6 weeks postoperatively. Beforesalvage surgery 4 of the patients required urinary tractdrainage and were chronically dependent on nephrosto-mies, ureteral stents and catheters. Following surgerynone of the patients required any long-term tubing. Bio-chemical failure, defined as the first of 2 consecutive PSAincreases, occurred in 3 patients 7, 26 and 32 monthsfollowing salvage surgery, whereas in 2 PSA remainedundetectable for 2 and 4 months following surgery, respec-tively.Two patients experienced long-term survival after salvage

surgery. One lived for 26 months but eventually died ofmetastatic disease. The other patient was still alive 55months after salvage surgery. Another patient died of meta-static disease 3.5 months following salvage surgery. Theother 2 patients were alive 5 and 7 months following salvagesurgery, respectively.Average hospital stay was 12 days (range 7 to 17) and the

average number of blood units given during surgery was 5(range 4 to 7). There were no perioperative deaths or any lifethreatening complications (table 2). Additional surgery wasnecessary in the patient in whom a continent urinary diver-sion was performed due to stomal stenosis. However, thepatient remained free of any cancer related local symptoms.

DISCUSSION

Although RP offers favorable cancer-free survival and ex-cellent local control in patients with organ confined disease,recurrence in the anastomotic region may develop with highGleason score and positive surgical margins.7, 8 Radiationtherapy in an adjuvant or salvage setting may improve localcontrol in these patients.9, 10 However, bulky local recurrencethat develops following RP alone or RP and salvage radiationtherapy represents a major urological problem. Such tumorshave the propensity to invade into adjacent organs, includingthe bladder and rectum, and become the source of debilitat-ing symptoms and significant morbidity. Although palliationbecomes a vital need in these circumstances, the availabletreatment options are limited. Systemic hormone treatmentand chemotherapy may provide temporary palliation but fulland long-term local control is often not achieved. Additionalradiation therapy (external beam or brachytherapy) couldput the patient at excessive risk for toxicity and it is lesslikely to provide effective local control due to the bulkiness ofthe tumor. Salvage radical surgery is technically challengingdue to the obliteration of anatomical plains resulting fromprevious surgery and radiation therapy. However, salvagesurgery has the potential of removing the tumor and elimi-nating associated symptoms.Salvage surgery following initial RP alone or following RP

and subsequent radiation therapy is a technical challenge tothe surgeon and a major procedure for the patient. Althoughin this series salvage surgery was associated with some post-operative complications and blood loss, no death or lifethreatening complications occurred. This provides prelimi-nary evidence that salvage surgery in the setting of previousRP is technically feasible and tolerable. In addition, resection

TABLE 1. Study subject clinical and pathological characteristics

Age at salvage surgery 60 53 66 71 66Yrs since RP 7 2 8 13 9RP Gleason score 9 6 6 7 9At diagnosis:PSA (ng/ml) 18.4 4.2 4.6 Not available Not availableClinical T stage T4a Not available T3b T3a T3a

Salvage radiation Adjuvant EB None Adjuvant EB Adjuvant EB, salvagebrachytherapy

Adjuvant EB

Chemotherapy Ketoconazole, doxorubi-cin, vinblastine,estramustine

Estramustine,ketoconazole

Taxotere, estramus-tine, carboplatin

None Ketoconazole, doxoru-bicin, vinblastine,estramustine

Presalvage surgery symptoms Hematuria, bladder out-let obstruction, renalfailure, bilat percuta-neous nephrostomies

None Hematuria, renalfailure, urinaryretention, perma-nent catheter �ureteral stents

Hematuria, rectalpain

Vesicorectal fistula,pelvic pain

Tumor size at surgery (cm) 8 � 8 � 10 3.8 � 2.5 � 2 4 � 3 � 2.5 Poorly defined* 8 � 6 � 8Involved organs Bladder, rectum Bladder, rectum,

uretersBladder, urethra Bladder, rectum Bladder, rectum

All 5 patients had positive initial RP surgical margins.* Tumor was part of poorly defined pelvic abscess and could not be measured.

TABLE 2. Clinical course in 5 patients with salvage surgery after initial RP

Salvage Type Hospital Stay(days) Complications Local Symptom

RecurrenceRehospitalization

(days)

Total pelvic exenteration, ilealconduit � end colostomy

17 Prolonged ileus None None

Anastomotic area resection* 8 Urinary tract infection, urinarydiversion incontinence

None† 7, stomal revision

Total pelvic exenteration, ilealconduit � end colostomy

12 Delirium Pelvic pain, fecaluria 26

Total pelvic exenteration, ilealconduit � end colostomy

16 None None None

Total pelvic exenteration, ilealconduit � end colostomy

13 None None None

* Due to recurrent tumor at vesicourethral anastomosis with no rectal involvement anastomotic area and bladder neck cuff were resected, bladder neck wasclosed and continent diversion was constructed.† Revision of the catheterizable stoma was necessary due to stomal stenosis but patient remained free of any local symptoms directly related to prostate

cancer.

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of the cancerous mass with the contiguous involved organsprovided effective palliation in all patients. Although theimpact of salvage surgery on survival is not clear, consideringour 2 patients who have experienced long-term survival gen-erates the hypothesis that achieving local control may pro-long survival, although it may not cure.Potential candidates who may benefit from salvage surgery

following initial RP include patients with symptomatic bulkylocal recurrence, especially when cancer recurred despiteadjuvant or salvage radiation therapy. Occasional patientsmay experience symptomatic local cancer recurrence follow-ing initial RP with or without subsequent radiation therapy.When the associated symptoms have a negative impact onpatient quality of life and the patients are sturdy enough towithstand an extended surgical procedure, the possibility of asalvage surgical procedure may be considered and a finaldecision may be reached individually following discussionwith the patient. To our knowledge the actual proportion ofpatients who might benefit from salvage surgery in the entirepopulation of patients with local cancer recurrence after RPis unknown but it is expected to be low.Our results are preliminary and further studies in larger

samples are necessary to address the impact of salvage sur-gery on palliation and disease specific survival in patients inwhom RP has failed with or without salvage irradiation. Inconclusion, our results provide preliminary evidence thatsalvage surgery performed in patients who have bulky localrecurrence of prostate cancer after previous RP is feasibleand safe, and it provides effective palliation.

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