Chemo day 2 - run baby run

Everyone stressed that I should drink as much as I could in the first 72 hours following chemo.  You don't want that cisplatin staying in the kidneys any longer than necessary.  So in addition to the two or three liters of fluid in the IV's that I received yesterday, I slugged back 4 liters of Powerade Zero.  Fortunately my bladder has mostly recovered from the second TURBT, and it doesn't hurt as much to expand or squeeze, because I am giving it a real workout, including in the middle of the night.  Given the choice between getting up every 2 hours and having undamaged kidneys, I choose to stand up for my body. 

I wonder if chemo interferes with REM sleep.  Usually I recall my dreams, but not last night.  All my cells (not just the cancer cells) are fighting off the drug-induced inability to reproduce, so maybe they didn't go into full sleep mode.  In any event, I woke up at about 5 am and could not go back to sleep.  I lounged in the hot tub and watched the sun rise while nursing another liter of Powerade, then decided if I should do some work while I can. 

The anti-nausea drugs appear to be working.  I occasionally feel a slight rolling in my GI tract, but nothing threatens to make an unwelcome appearance.  A friend brought over a wonderful meal last night, so I enjoyed a dinner with my family and had a healthy appetite.  Enjoy it while it lasts, I tell myself.  After my cancer diagnosis I stopped my diet (right before Thanksgiving), and I have added more than 10 pounds during the holiday feasting.  I rationalized that I'll be rid of it soon enough.

I do have a quandry, however.  I have been told that I might have to avoid my favorite foods during chemo, because the association of those foods while feeling nauseated might create a permanent aversion to those foods.  So, should I force myself to each fresh baked, warm, gooey chocolate chip cookies during chemo, and thereafter be forever sickened at the sight?  As those cookies are my primary drug of choice, I suspect it might be a good thing to do.  But it would be a huge sacrifice.  I'm not sure if I can do it. 

First day of chemo

First day of chemo.  Jennifer drove me to the GW Cancer Center. It's a busy place, where patients hurry up and wait. 9:05 am: Check in, wait. 9:20: Vitals, wait. 9:40: Blood draw, wait.  9:55: Get called back to see the oncologist, wait.  10:20: Oncologist arrives; we talk about the treatment plan (more below), then go back out to reception and wait.  10:55: Get called back to the chemo delivery area, wait. 11:35:  the nurse hooks me up to a saline pump for hydration.  No drugs yet.  12:05:  I start the anti-nausea meds (Emend, 150 mg 5 mL; Aloxi 250 mcg; Dexamethasone 12 mg).  Come on, hurry up and poison me. I'm an impatient patient.

During all of this waiting, Jennifer finds the social worker and makes a new friend.  Jennifer is planning on getting her Master's in Social Work this fall, and finds this stuff very interesting.  I'm less of the touchy-feely sort, but acknowledge that social work and emotional support can provide a crucial component to a recovery plan.  I like to think that I am relatively well-equipped with tools and techniques to handle this process, but at times I know that I am a stranger on a solitary journey through what for me is an uncharted land.  I appreciate the guidance of those who have gone before, but know that each person's terrain varies according to their disease, predisposition, attitude, and emotional state.  Their journey is not mine, and the maps of others are of limited use, for they can only provide suggestions of what I might encounter. I am forging my own path with this disease, not willingly, but so it is with life.

 Anyway, Dr. Aragon-Ching told us that she was going to modify the the treatment plan. Although the standard GemCis regimen calls for 3 weeks of chemo, followed by one week off, she said that in her experience, almost no one is able to tolerate the third week of chemo. (Her actual words were, "I've never had a patient be able to do the third week."). Instead of having people set up expectations then be thrown off, she said that I should plan on having chemo on days 1 and 8, then have my third week off, then repeat 4 times. This means that I might be done with chemo by late April instead of later May. It also means that my surgery could be in May instead of June.  All of this remains subject to change - if there is anything that I have heard in the past weeks as I prepare for chemo, it is flexibility. 

Today I am starting off with a trio of anti-nausea drugs, followed by a steroid, then the gemcitabine (Gemzar), followed by the cisplatin.  The cisplatin is the hardest on the system, and is responsible for most of the side effects, such as nausea, changes of taste, weariness, as well as risks of kidney damage or nerve damage. While the side effect rate is relatively low (1% or so), it is serious enough that they carefully monitor for it.  The list of side effects for both drugs is 8 pages of fine print. I wonder how many people actually read it.

At 1:10 pm, I finally start the main event:  Gemcitabine (2380 mg) for 30 minutes, followed by 60 minutes to infuse the Cisplatin (160 mg), which is mixed in with magnesium sulf 50% (1000 mg) and Mannitol 25% (12500 mg).  The chest port seems to be working just fine -- unlike an IV in the arm, I have zero discomfort or sensation of the drugs entering my body. The pump has a repetitive rhythm as it slowly pushes the life giving poison into my veins. I lean back in the easy chair, flip up the leg rest, pull the blanket around me, put on my noise canceling headphones, crank up Clapton on my iPhone, and close my eyes.  I'll enjoy it while I can. 

Fifteen minutes later, a piercing shriek jolts me awake.  The fire alarm is going off, and a disembodied voice is advising everyone to evacuate the building via the stairs ("do NOT use the elevator!"). I begin to contemplate how long the batteries on the IV pump will last, and whether to carry the bags or carry the pole down the stairs, until the nurses walk around and tell us to stay put.  They advise, "most of the time it's a false alarm." I don't know if I should be reassured or not, but push up the volume on Slow Hand and try to close my eyes, although the flashing strobe intrudes on my attempt to rest. After about 10 minutes, the alarm is silenced, and I'm back to the low growling of the IV pump. 

By 2:40, all the cisplatin is in my body.  The nurse hangs another bag of saline and tells me that I need more fluids.  Drink as much as you can, she says.  You don't want any of this stuff in your kidneys any longer than necessary.  The more fluids you push through your system, the better.  Maybe I'll be done by 3:30 or 4 pm. I don't think I'll go into the office today.

I'm glad that my bladder has mostly recovered from the second TURBT - it was badly scarred with the removal of a chunk of muscle around the site of the tumor base, as well as 10 other scars created by the removal of those smaller tumors.  It didn't want to expand as much as it used to, leading me to conclude that the effect of the two surgeries was to change the gender of my bladder.  My capacity dropped from a gallon to a thimble.  Welcome to our world, said Jennifer, and every other mother who heard this report.  But that's not all.  For several weeks after, contracting the bladder during urination would cause a sharp pain as the muscle protested. I dreaded having to urinate, and wondered if this was a way of my bladder telling me that it was ok with my decision to get rid of it.  What a vengeful organ.  But more recently it's been less painful.   The relationship between my bladder and me may be like other aspects of life, perhaps: the initial idea of ending a long-standing relationship can be marked by sharp pain and acute discomfort, but as time passes, you get more acclimated to the idea.  I'm now at peace with the idea that my bladder will be removed in a few months. I understand that I have a highly aggressive cancer laced throughout the structure of that organ, and keeping it is like having a ticking time bomb in my body. The chemo that I am having is intended to attack all of the cancer wherever it might be, but it is not the primary treatment for this cancer - it is adjuvant to the proven treatment of removing the diseased organ, as well as the surrounding organs and tissue that are likely to hold the carcinoma. Begone, you diseased organ, you specter of death, you foul imposter, you useless thing. 

Humm, maybe the drugs are affecting me more than I realize . . . .   

I get home at about 5 pm, and as I take off my outer shirt, my new iPhone 4S slips out and drops on the tile floor of my kitchen and shatters the glass.   What a pain.  Fortunately, AmEx's purchase assurance will cover the cost, and I can either have Verizon replace it or Apple repair it.  If this is the worst thing that happens during chemo, then I can survive this.  But if this is a harbinger of things to come, then I'm not going to be a happy camper. 

Chemo port placement

This morning I went to GW hospital and had a port placed in my chest, which will make the delivery of chemotherapy much easier and far fewer blown veins and looking like a drug user.  See Wikipedia for details.  Unlike my TURBTs where I was totally sedated, for this I had "twilight sedation" - no intubation, but I'd be feeling no pain.  Sure enough, as soon as they turned up the drip, I could hear the voices talking, but had no sense of time, and really didn't care what was happening to my body.  After a few minutes, the drip stopped, and I asked how long it had been - it was more than an hour!  The nurse told me that I should "not make any legal decisions today, or even send work emails."  Sounded like CYA to me.  I decided I'd listen to my body, and felt pretty good as I left the hospital.  I walked to my office, had two conference calls and two meetings, and of course sent dozens of emails.  Yes, I was tired when I got home, but I'm that kind of patient.

How to help

In response to multiple inquiries from family and friends on how they can best help, I shared the following:

1.  A family meal delivered each Monday afternoon/evening (I'll be getting chemotherapy each Monday, and a chemo session can take hours.  Jennifer will be with me, and not having to worry about a meal that evening would be most appreciated).  We're being told that my meals should be high in protein and with lots of fruits and vegetables; capable of being eaten in smaller portions as my appetite will come and go depending on my nausea and how much damage the chemo does to the lining of my stomach; the meals should avoid spicy foods, red meats, processed sugar, or high carbs. 

2.  In the event of heavy snow, having people to come as help the boys shovel, as I likely will be rather weak for the next few months. 

3.  I will be at increased risk of infection while having chemo.  I don't know how it will be possible, but it would help if people at church would be even more vigilant of good hygiene, e.g., frequent washing of hands, use of hand sanitizer (maybe have some sanitizer bottles available in the foyers, classrooms, etc.).  We're doing this at home, and will be encouraging visitors likewise to be mindful. 

4.  Continued ward support of my family.  Individual meaningful invitations to Garrett, Kirsten, and Spencer to spend some one-on-one time with peers or mentors, and giving them an opportunity to express themselves without pushing.  Also, occasional thoughtful cards or other expressions of love and concern to each family member are appreciated.  Those tender mercies can make amazing differences in our moments of sorrow. 

5.  Most importantly, fervent prayer and faith, for it is the Lord who is preserving me from day to day, by lending me breath, that I may live and move and do according to my own will, and even supporting me from moment to moment.

Defining the course of treatment

Since my second surgery on Jan. 5, we have been actively consulting with doctors at three different hospitals to determine the best course of treatment.  Today Jennifer and I spent the day at Hopkins; in the past couple of weeks we have had numerous consultations with doctors from Hopkins, Mass General, and GW.  I have been most impressed with the professionalism of all of these doctors, as they have checked their egos and collaborated to determine what is the best treatment for me. 

I have learned that my case is highly uncommon for a number of reasons:  (1) fewer than 5% of bladder cancer cases occur in patients under age 50; (2) only 24% of all bladder cancers are muscle-invasive; (3) fewer than 7% of muscle-invasive cancers have the micro-papillary features (a particularly nasty form of transitional cell carcinoma) that the pathologists have found in my case; and (4) fewer than 1% of bladder cancer patients present with as many different tumors occurring at the same time - I had the one major tumor that was removed on 12/1/11, and 10 other smaller ones removed on 1/5/12. One of my consulting doctors from Mass General - a national authority with 45 years experience with treating bladder cancer - said he could not recall another case that was like mine. While I'm not convinced this is a good thing, it was enough to get his attention and very helpful and in-depth consultation of him and his team (without asking for any insurance information!). 

The upshot is that the doctors at Mass General, Hopkins, and GW all agree that my bladder is badly compromised by the cancer, and should be removed. The doctors also agree that I should first have several courses of intravenous systemic chemotherapy with gemcitabine and cisplatin.  This chemo regimen will involve 3 or 4 courses, and each course will last for 28 days (chemo on days 1, 8, and 15, then a week off to recover).  They also agree that I should not have radiation therapy at this time, but instead wait and see how I respond to the chemo, and to see what the pathology reveals after the surgery.  They also agree that having chemo at GW is fine, both because the oncologist there is very well regarded in this field, and because there is unanimous agreement on the chemo regimen.

Thus, I am scheduled to start chemo next Monday, Jan. 30; I will have an IV port placed in my chest on Friday, Jan. 27. I am told that there is a wide variation on how patients tolerate this type of chemo. While the first week of each regimen is the hardest, some patients are able to work relatively normal schedules during the other weeks, while others feel crappy the whole time.  Some patients lose their hair; others do not.  Most patients lose weight, but some do not, and a few gain weight because the stomach stops talking to the brain (something that apparently happened to me years ago . . .).  The doctors stress flexibility and to not overcommit - advice I fully intend to follow.

Assuming I am able to tolerate the full 4 courses of chemo, I would complete it in mid-May. I would have several weeks to recover, then likely will have surgery in mid-June to remove the bladder, prostate, and surrounding lymph nodes.  I also will have a neobladder created from other tissue (there are several options on what tissue is used to construct it; Google neobladder if you want to know more).  The intent of the neobladder is to create an alternative reservoir to hold the urine and otherwise use all the original plumbing. I'm told that I’ll have to learn to use some different muscles and techniques to empty the neobladder.  Recovery from that surgery is about 2 months, plus I can look forward to several additional months of physical (peesical?) therapy.

Thereafter, I will be closely followed to see if there is any hint of metastasis. This type of cancer loves to spread, and if it does, it's very bad. About 25% of patients with stage 2 TCC eventually have it spread, despite the chemotherapy. More optimistically, there is a 75% chance that I will have a full recovery. While it will be a long slog this year, I have confidence that I'm getting the best care possible and am in the best position to beat this thing.

Thank you once again for your ongoing support, faith, and prayers. It is in circumstances such as this that the true character of people are revealed, and I am gratified that my family, friends, and colleagues have shown themselves to be true mensches. 

Acceptance

My friends have asked how I am coping with my cancer.  I have told them that, based upon some experiences with my son and his battles with drugs and alcohol (he's currently clean and sober), I learned to accept the things I cannot control, and cancer is something I cannot control.  I can control my reaction to it, and the choice of doctors, and what treatments I choose to do.  But it is what it is. No anguish or grief here - just acceptance of what I can't control and courage to face what is. Better to find joy than sorrow with whatever time we have.

Catheter out!

I do not like living with a catheter.  I usually fall asleep on my stomach, but it's very difficult to do that comfortably with a catheter connected to a long nighttime bag.  Fortunately, I requested that I get a smaller catheter before I left the hospital, so the #24 was replaced by a #16, which was far more tolerable.  But still, It's better to not have one that have one . . .

Follow-up from second TURBT

A quick update on my cancer:  Last Thursday, I had a another TURBT procedure at GW to remove the bladder muscle that was located under the tumor that was removed on December 1.  In addition, the doctor also removed a number of smaller nodules of less invasive cancer that were scattered elsewhere in the bladder.  The tissue was sent to the pathologist for testing.  Today, Jennifer, Chelsea and I met with the urologist, who had the pathology results.  The pathology confirmed the earlier diagnosis of high grade invasive urothelial carcinoma.  For the scattered carcinoma in-situ, the pathology found that there was invasion into the lamina propria, but not into the bladder muscle (e.g., T1+Tis). The pathology under the tumor base found that the principal tumor had invaded into the bladder muscle (muscularis propria, or Detrusor muscle).  This was the key missing piece of information from the first procedure, and indicates that the primary cancer had deeply invaded the muscle (Stage 2b).  This means that my cancer has been definitively staged at pT2b+ T1+Tis, N0, M0.

What this means from here has yet to be determined, however.  Apparently the entire field of urology is in the middle of a sea change.  The traditional treatment for this type of muscle invasive bladder cancer is to remove the bladder, prostrate, and surrounding lymph nodes (radical cystectomy), and also have systemic chemotherapy and radiation therapy.  As recently as two years ago, this was the standard of care.  The downside of radical cystectomy is the loss of the bladder, and about a third of all patients are left impotent.  In the past 18 months, however, more than a half-dozen studies have suggested that improvements in chemotherapy suggest that radical cystectomy is unnecessary.  Instead, those studies suggest that, after the tumor has been removed, immediate (pre-adjuvant) chemotherapy and radiation, combined with careful follow-up, can be just as effective as radical cystectomy, without any of the debilitating side effects.  Because these studies are so new, however, there is some controversy, especially among long-time urologists who have been trained to cut everything out that might have cancer.  (As the chief urologist at Hopkins told me two weeks ago, "when your only tool is a hammer, everything looks like a nail.")

My urologist has acknowledged all of this recent information, and recommended that I meet with GW's oncologists and radiologists, and also seek a full-blown second opinion from the Hopkins team.  He also suggested that I consider talking to Sloan-Kettering or the Cleveland Clinic.  In response to Jennifer's questions of, if this were your bladder, what would you do?", he said that the most important thing was to select a team that will coordinate and direct my treatment.  He said that the leading cancer centers such as Hopkins, Cleveland Clinic, or Sloan-Kettering, were very good about adopting a multi-disciplinary team approach.  In what I thought was a candid admission, he tacitly acknowledged that most other places, including GW, were not that good at managing cases on a team approach.  He also said that, based upon the recent advances, the oncologist, and not the urologist, likely would be the key person directing the team. 

By all accounts, the next treatment likely will be pre-adjuvant systemic chemotherapy.  Apparently the type of chemo has been evolving as well; MVAC is now less favored than GC, and recent studies of paclitaxel with GC suggest that it can be even more effective.  When I met with GW's oncologist a couple of weeks ago (who just wrote a chapter of chemo for bladder cancer), she noted that very recent studies have suggested that some cancers can be sequenced and designer chemotherapies can be developed that best target the specific type of disease.  I'm meeting with her again tomorrow, and I'm also going to have another consult with the team at Hopkins, then we'll take it from there.  Stay tuned! 

Once again, thank you for your ongoing expressions of support, faith, and prayers.  I draw considerable strength knowing that there are so many people out there who are pulling for me.  I am grateful to all of you for your ongoing care.  I am grateful that I can count on the support of my family, friends, employer, and church, and am comforted that I don't have to bear this burden by myself.  This experience has reaffirmed the importance of strong human relationships, the power of compassion, and the inner peace that is grounded upon faith in God. 

Detailed research on treatment options

Here’s a long list of questions and research that I have compiled this weekend.  My goal is to have these questions answers in the next couple of weeks, so I can know what is the best course of treatment.  

Treatment options:

1.     Radical cystectomy: pros & cons

a.     Prognosis

b.     Is RC still the standard of care?  Or is the standard evolving?

c.      Prostate cancer research: too much unnecessary surgery; standard of care recently has changed.  Why is bladder cancer different?

d.     Therapeutic interventions targeting organ preservation in muscle-invasive bladder cancer: a review, Clin Transl Oncol. 2011 May;13(5):315-21. (“Nowadays in modern oncology there is a tendency towards therapies that target organ preservation. Organ preservation protocols have become standard in the treatment of laryngeal carcinoma, oesophageal cancer, breast carcinoma and soft tissue sarcomas. The three-combined therapy consisting of a transurethral resection of the bladder tumour followed by concomitant chemoradiotherapy has been shown to be an attractive alternative for bladder preservation in selected patients with muscle-invasive bladder cancer. In order to evaluate the organ preservation approaches in muscle-invasive bladder cancer we have conducted a comprehensive literature review. Data reported from the studies have shown that bladder preservation therapy with a trimodality approach is safe and effective. Moreover, such an approach provides patients with the opportunity to maintain an intact and functional bladder with a survival rate similar to that of radical cystectomy.”) www.ncbi.nlm.nih.gov/pubmed/21596659

 e.     Why remove bladder, prostate, and lymph nodes?

 f.      If T0 is confirmed via TURBT, then why RC?

 g.     Is it true that 50%+ of recurrence is in distant locations?  So RC has zero effect in those cases? 

h.     Why no double-blind clinical trials comparing RC to bladder preservation?  Are there any currently underway?

i.       Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder, Int J Radiat Oncol Biol Phys. 2011 Oct 20.  (“A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significant difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. . . . Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.”)

 2.     Bladder preservation: pros & cons

 a.     Prognosis

b.     Do recent studies suggest prognosis is about the same? 

 c.      Chemoradiotherapy for muscle-invasive cancer: Methods, surveillance and results. An update from the committee of cancer from the French National Association of Urology. Prog Urol. 2012 Jan; 22(1):13-6. Epub 2011 Nov 9 (“Radical cystectomy is the treatment of choice for non-metastatic, muscle infiltrating bladder cancer. However, bladder-sparing approaches can be discussed in carefully selected patients. Bladder-preservation protocols aim to guaranty local control and survival with a functional bladder and a good quality of life. The ideal candidate for bladder-preservation therapy is a patient with a small tumor, stage T2, in whom a complete trans-urethral resection of the bladder tumor is achievable, who has no associated carcinoma in situ or hydronephrosis, and who is medically fit to receive chemotherapy. The 5- and 10-year survival rates for muscle-invasive tumors are approximately 50% and 35%, comparable to the results achievable with cystectomy. Approximately 80% of long-term survivors will preserve a native bladder, and approximately 75% of them will have a normal-functioning bladder.”) http://www.ncbi.nlm.nih.gov/pubmed/22196000

 d.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“Bladder preservation may be accomplished in appropriately selected patients with muscle-invasive UCB without compromising outcomes using a trimodality approach with maximal transurethral resection (TUR) followed by concurrent chemotherapy and radiation therapy. Optimal application of this approach requires close coordination among the urologist, medical oncologist, and radiation oncologist. Appropriate candidates have T2-4a and clinically node-negative disease, primary tumors amenable to complete or near complete TUR, no hydronephrosis and adequate renal function to tolerate cisplatin. Salvage cystectomy is required for persistent or recurrent disease at repeat cystoscopy, either during or after chemoradiotherapy (CRT), and is typically necessary in approximately one-third of patients [39]. The largest single-institution series from the University of Erlangen (415 patients) showed that early tumor stage and a complete TUR are the most important factors predicting CR and survival [40]. Chemotherapy alone is not an appropriate treatment for muscle-invasive UCB being treated for cure. . . . In appropriately selected patients, bladder preservation with TUR, chemotherapy, and radiation are feasible and produces high rates of CR with acceptable disease control and OS with intact bladders. Concurrent cisplatin-based radiation has the most supporting data, but newer agents are being evaluated. The value of induction chemotherapy has not been established, and the value of postradiation adjuvant therapy, while conceptually attractive, lacks sufficient data for definitive conclusions. Careful, continued surveillance with cystoscopy both during and after CRT is mandatory.”) www.ncbi.nlm.nih.gov/pmc/articles/PMC3217602/

 e.     Long-Term Outcomes of Selective Bladder Preservation by Combined-Modality Therapy for Invasive Bladder Cancer: The MGH Experience, Eur Urol. 2011 Nov 12. www.ncbi.nlm.nih.gov/pubmed/22101114

BACKGROUND:

Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown.

OBJECTIVE:

Report long-term outcomes of patients with muscle-invasive BCa treated by CMT. 

DESIGN, SETTING, AND PARTICIPANTS:

We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2-4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr.

INTERVENTIONS:

Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC-60 for less than CR and 42 for recurrent invasive tumors.

MEASUREMENTS:

Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method.

RESULTS AND LIMITATIONS:

Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2=74%, 67%, and 63%; T3-4=53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3-4=41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p<0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity.

CONCLUSIONS:

CMT achieves a CR and preserves the native bladder in >70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients.

 

f.      Primary cT2 bladder cancer: a good candidate for radiotherapy combined with cisplatin for bladder preservation, Jpn J Clin Oncol. 2011 Jul;41(7):902-7. Epub 2011 May 25. http://www.ncbi.nlm.nih.gov/pubmed/21616918

BACKGROUND:

Bladder preservation therapy (BPT) has been attempted for patients with localized muscle-invasive bladder cancer. However, the indication for BPT has not yet been established. To identify patients who are good candidates for BPT, we evaluated our long-term experience with chemoradiation therapy (CRT) for bladder preservation.

METHODS:

Between 1994 and 2009, 82 patients with bladder cancer (clinical stage T2-N0M0) without concurrent upper urinary tract urothelial cancer were treated with CRT. Before CRT, the patients had a biopsy or resection of the tumor by transurethral resection (TUR). The response to CRT was evaluated by TUR, urine cytology and computed tomography.

RESULTS:

Thirty-two cases (39.0%) had a pathological complete response (pCR) that was defined as no microscopic residual tumor in the bladder. After TUR, 69 cases (84.0%) achieved local control of the cancer, which was considered as a clinical complete response (cCR). There was no significant association between achievement of pCR and examined parameters. The long-term results of CRT were evaluated in cCR cases. The median follow-up was 42.8 months (range, 4.1-155.1). The 5-year overall survival rate was 77.7% and 5-year progression-free survival rate was 64.5%. Clinical T stage and type of tumor (primary or recurrence) were predictive factors for overall survival as well as progression-free survival. In addition, primary cT2 cases had significantly better prognosis than cT3-4 and recurrent cases in overall survival and progression-free survival (P= 0.008 and P= 0.046, respectively).

CONCLUSION:

Cases with a primary cT2 tumor could be good candidates for BPT with radiation combined with cisplatin.

g.     Significantly fewer side effects?

h.     Current management of muscle-invasive bladder cancer, Clin Transl Oncol. 2011 Dec;13(12):855-61 (“Management of muscle-invasive bladder cancer (MIBC) has changed little in the last twenty years. The gold standard treatment is still cystectomy, but it has a significant negative impact on quality of life. Bladder-preservation strategies can be used in some cases but patient selection for this approach remains unclear. New chemotherapy and biologic agents in combination with surgery or radiotherapy could improve results and these possibilities are currently under investigation.”) http://www.ncbi.nlm.nih.gov/pubmed/22126728

 

i.       Selective organ preservation in muscle-invasive bladder cancer: Review of the literature, Surg Oncol. 2011 Nov 14.  (“The standard of care for transitional-cell carcinoma of the bladder with invasion to the muscularis propria is radical cystectomy with bilateral pelvic lymph node dissection. However, currently there is a tendency for organ preservation in selected cases of muscle-invasive bladder cancer. Trimodality treatment, including transurethral resection of the bladder tumor (TURBT), radiation therapy and chemotherapy, has been shown to produce 5-year and 10-year overall survival rates comparable to those of radical cystectomy. The current 5-year overall survival rates range from 50 to 67% with trimodality treatment, and approximately 75% of the surviving patients maintains their bladder. After trimodality treatment complete response is obtained in more than 70% of patients with muscle-invasive bladder cancer. Clinical criteria helpful in determining patients for bladder preservation include such variables as small tumor size (<2cm), early tumor stage (T2-T3 disease), a visibly and microscopically complete TURBT, absence of ureteral obstruction, no evidence of pelvic lymph node metastases, and absence of carcinoma in situ (Tis). The close collaboration of urologists, radiation oncologists and medical oncologists is of paramount importance in succeeding in bladder preservation.”) www.ncbi.nlm.nih.gov/pubmed/22088598

 j.       Why not seek to keep bladder, than do salvage RC if needed?

 3.     Partial cystectomy: pros & cons

a.     Prognosis

b.     Why generally not favored?

 4.     Pre-adjuvant therapy

 a.     Must RC decision be made first?

 b.     What does pre-adjuvant therapy typically include?

 c.      Chemo (see below) 

 d.     Pre-adjuvant radiation

                                               i.     Pros & cons

                                              ii.     Does it preclude neobladder option?

                                             iii.     Image-guided radiation therapy for muscle-invasive bladder cancer, Nat Rev Urol. 2011 Nov 8;9(1):23-9. doi: 10.1038/nrurol.2011.173. “(Organ preservation protocols that incorporate chemoradiotherapy have shown good efficacy in bladder cancer. Owing to changes in rectal filling, urinary inflow and subsequent bladder volume with bladder wall deformations, irradiation must take into account interfractional and intrafractional internal target motion. Growing evidence suggests that image guidance during irradiation is essential in order to appropriately treat bladder cancer in this way. We performed a literature search on the imaging techniques and margins used for radiation therapy planning in the context of whole-bladder and partial-bladder irradiation. The most common image-guided radiation therapy (IGRT) method was based on cone-beam CT using anisotropic margins. The role of cine-MRI for the prediction of intraindividual bladder changes, in association with cone-beam CT or ultrasonography, is promising. Drinking protocols, diet and laxatives were used in most cases to minimize large variations in bladder size and shape. IGRT is crucial for avoiding tumor undercoverage and undue toxicity during radiation therapy for bladder cancer. IGRT-based adaptive radiation therapy can be performed using cone-beam CT or ultrasonography: modeling of bladder changes with cine-MRI or other imaging techniques might also be useful for facilitating adaptive radiation therapy with personalized margins.”) www.ncbi.nlm.nih.gov/pubmed/22064641

 e.     BCG

                                               i.     Does it ever make sense to use BCG with MIBC? 

                                              ii.     Why not BCG, then chemo?

                                            iii.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“Given the experience in nonmuscle-invasive UCB with BCG and interferon, there has been interest in the application of immunotherapy to more advanced bladder cancer as well. Ongoing trials are evaluating a human chorionic gonadotropin-β vaccine (Celldex Therapeutics, CDX1307-03, NCT01094496), and the anticytotoxic T-lymphocyte-associated antigen 4 antibody ipilimumab (NCT00462930), both in the neoadjuvant setting.”) www.ncbi.nlm.nih.gov/pmc/articles/PMC3217602

 f.      Interferon

 5.     Chemo: how to decide which type?

 a.     Molecular markers?  How to assess, measure, and design treatment?

                                               i.     HER2/neu overexpression

                                              ii.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“Her2/neu is variably expressed on urothelial carcinomas and has been evaluated as a possible therapeutic target. One study screened 109 patients with advanced UCB and found that Her2-positive patients (52%) had more metastatic sites and higher rates of visceral disease than Her2-negative patients [85]. Forty-four patients were treated with trastuzumab, paclitaxel, carboplatin, and gemcitabine with an overall response rate of 70% with 57% confirmed responses. Median survival was 14.1 months. Toxicities included 93% grade 3-4 myelosuppression, 14% grade 3 sensory neuropathy, 22.7% grade 1–3 of cardiotoxicity (4.5% grade 3), and 3 therapy-related deaths.”) www.ncbi.nlm.nih.gov/pmc/articles/PMC3217602

                                             iii.     Targeted therapy for locally advanced and/or metastatic bladder cancer, Prog Urol. 2008 Jul;18(7):407-17. Epub 2008 Jun 26. (“Due to their molecular heterogeneity, optimal targeted therapy of bladder cancers will require the combined use of several molecules. Modulation of signalling pathways by these new molecules can restore chemosensitivity to cytotoxic drugs, which can then be associated with targeted therapy.”) http://www.ncbi.nlm.nih.gov/pubmed/18602599

                                             iv.     HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder, British Journal of Cancer (2003) 89, 1305–1309, 30 September 2003 (“Anti-HER2/neu therapy might be of use in the treatment of TCC.”) http://www.nature.com/bjc/journal/v89/n7/full/6601245a.html

                                              v.     Prognostic impact of HER2/neu protein in urothelial bladder cancer. Survival analysis of 80 cases and an overview of almost 20 years' research, J BUON. 2009 Jul-Sep;14(3):457-62. (“Conclusion: HER2 overexpression represents a prognostic factor for adverse disease outcome.”) http://www.ncbi.nlm.nih.gov/pubmed/19810139

 b.     Epidermal growth factor receptor (EGFR) expression http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217602/table/tab2 (“Table 2 summarizes the ongoing clinical trials with targeted agents in urothelial carcinoma. Epidermal growth factor receptor (EGFR) expression has been demonstrated on 50% of bladder tumors [86], and trials are ongoing with cetuximab. Vascular endothelial growth factor (VEGF) receptors are another potential target. Trials are evaluating the use of bevacizumab both in the metastatic and neoadjuvant setting as well as other anti-VEGF agents. However, a recent phase II experience with sunitinib in advanced UCB was disappointing, with only 4 responses in 77 patients [87].”)

 c.      Vascular endothelial growth factor (VEGF) receptors http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217602/table/tab2

 d.     Polysomy 17

 e.     Steve Jobs’ had his pancreatic cancer sequenced, which assisted his treatment.  Can same be done here?

 6.     Chemo delivery options

 a.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“UCB is considered a chemotherapy-sensitive disease with response rates in fit patients approaching 50%. Systemic chemotherapy remains the standard of care for patients with metastatic UCB. The principle challenge in this context is the high frequency of impaired performance status, renal dysfunction, and other comorbidities.”)

 b.     Intravesical

                                               i.     What type of drugs?

 c.      Systemic

                                               i.     IV

                                              ii.     oral 

 d.     Why not both intravesical and systemic?

 e.     Possible new option: balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation. Neoadjuvant and adjuvant chemotherapy for locally advanced bladder carcinoma: Development of novel bladder preservation approach, Osaka Medical College regimen.   Int J Urol. 2012 Jan;19(1):26-38. doi: 10.1111/j.1442-2042.2011.02856.x. Epub 2011 Nov 13 (“Cisplatin-based chemotherapy has been widely used in a neoadjuvant as well as adjuvant setting. Furthermore, trimodal approaches including complete transurethral resection of the bladder tumor followed by combined chemotherapy and radiation have generally been performed as bladder preservation therapy. However, none of the protocols have achieved a 5-year survival rate of more than 70%. Additionally, the toxicity of chemotherapy and/or a decreased quality of life due to urinary diversion cannot be ignored, as most patients with bladder cancer are elderly. We therefore newly developed the novel trimodal approach of "combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects ("Osaka Medical College regimen" referred to as the OMC regimen). We initially applied the OMC regimen as neoadjuvant chemotherapy for locally advanced bladder cancer. However, since more than 85% of patients with histologically-proven urothelial cancer achieved complete response with no evidence of recurrence after a mean follow-up of 170 (range 21-814) weeks, we have been applying the OMC-regimen as a new approach for bladder sparing therapy. We summarize the advantage and/or disadvantage of chemotherapy in neoadjuvant as well as adjuvant settings, and show the details of our newly developed bladder sparing approach OMC regimen in this review.”) www.ncbi.nlm.nih.gov/pubmed/22077821

 7.     Drug choices: how to decide, pros & cons

 a.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“Gemcitabine and cisplatin is the current standard of care for first-line treatment in fit patients with metastatic disease. Optimal second-line therapy remains undefined, and targeted agents are under investigation. Clinical trial participation should be encouraged in patients with urothelial carcinoma of the bladder to help improve treatment regimens and outcomes.”) http://www.ncbi.nlm.nih.gov/pubmed/22125450

 b.     MVAC

                                               i.     Methotrexate

                                              ii.     Vinblastine

                                            iii.     Doxorubine

                                            iv.     Cisplatin

                                              v.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“Historically, the standard first-line therapy for fit patients in the combination chemotherapy era has been MVAC. MVAC has been compared to both cisplatin alone and a combination of cisplatin, cyclophosphamide, and doxorubicin (CISCA) with superior response rates and OS [53, 54], with median survival of 12.5 months [53]. However, MVAC is associated with significant toxicity including myelosuppression, neutropenic fever and sepsis, mucositis, nausea, vomiting, and a 3-4% toxic death rate [53, 55]. These side effects and the complex schedule often limit its use.”) http://www.ncbi.nlm.nih.gov/pubmed/22125450

 c.      GemCis

                                               i.     Gemcitabene

                                              ii.     Cisplatin

                                            iii.     Update on chemotherapy in the treatment of urothelial carcinoma, ScientificWorldJournal. 2011;11:1981-94. Epub 2011 Oct 26. (“Due to significant toxicities with MVAC, other regimens have been investigated in the first-line metastatic setting. A phase III trial of 220 patients demonstrated that MVAC was more effective than docetaxel and cisplatin with improved response rates, time to progression, and median survival [57]. After encouraging phase II data [58–60], gemcitabine and cisplatin (GC) were compared to MVAC in a randomized phase III trial with 405 patients [61]. While the study was not powered to show equivalency, overall response rate, time to progression, and median survival were similar for both regimens, with less grade 3-4 neutropenia, neutropenic fever, sepsis, mucositis and alopecia in the GC arm. The toxic death rate was 3% with MVAC and 1% with GC. Long-term followup after 5 years demonstrated continued similar survival between the two arms [62]. Based on these results, GC is now considered the standard-of-care first-line therapy for fit patients with metastatic bladder cancer. . . Based on the data from the metastatic setting where gemcitabine and cisplatin (GC) has replaced MVAC as preferred treatment due to similar response rates and reduced toxicity, GC has been studied in the neoadjuvant setting in small, nonrandomized trials. Herchenhorn et al. reported a single institution study with 3 cycles of neoadjuvant GC in 22 patients with T2-T4 disease and found a combined partial and complete radiographic response in 70% of patients [23]. Pathologic CR was found in 26.7% (4/15) of the patients who went onto surgery. Treatment was well tolerated with no deaths attributed to chemotherapy. With 26 month followup, the estimated median OS was 36 months. In a retrospective review from the Memorial Sloan-Kettering Cancer Center, 42 patients were treated with 4 cycles of neoadjuvant GC, with downstaging to pT0 in 26% of patients and to no residual muscle-invasive disease (<pT2) in 36% [24]. All the patients achieving <pT2 remained disease-free at the median followup of 30 months. However, despite widespread adoption, neoadjuvant GC has not been validated in prospective, randomized studies.”) http://www.ncbi.nlm.nih.gov/pubmed/22125450

 d.     GemCis+Paclitaxel.  “Attempts to improve upon this regimen have included adding a third drug to GC. The SOGUG found the combination of paclitaxel, gemcitabine, and cisplatin (PGC) to be feasible with an overall response rate of 77.6% (with 28% CRs) in 61 patients [63]. To more fully evaluate this tactic, the EORTC 30987/Intergroup Study randomized 627 patients to either PGC or GC with a primary endpoint of OS [64]. The first report in abstract form demonstrated an improved response rate with PGC (57% versus 46%) but only a trend in favor of OS (15.7 versus 12.8 month, P = 0.10). Of note, the study was powered to detect a 4-month difference in survival. There was more thrombocytopenia on the GC arm, while PGC was associated with increased leukopenia, neutropenia, and febrile neutropenia.”  Id.

 e.     CMV

Second TURBT

Here's an email to family that I tapped out on my iPhone while in post-op:

I'm in post-op now.  I am told that the surgery went well. They removed all the superficial lesions, and scooped out the muscle around the site of the original tumor. The pathology will be done on Monday or so. They are going to hold me overnight for observation. Ugh. I will have the catheter through Monday at least. Ugh again. We'll know the staging next week. Until then, it's just a waiting game. Thank you for all your support, faith and prayers.