With or Without a Scalpel

Cutting-Edge Treatments in Prostate, Breast and Blood Cancer

While the eradication of cancer is still a dream, new treatments – some that involve a scalpel but many that do not – provide hope for a longer life expectancy coupled with a higher quality of life. Maryland Physician Magazine spoke with three Maryland cancer experts – Jonathan J. Hwang, M.D., Theodore N. Tsangaris, M.D. and Maria R. Baer, M.D. – to learn about the latest developments in the fight against prostate, breast and blood cancers.

Prostate Cancer: Good News on Multiple Fronts

Dr. Hwang, M.D., director, Robotic Surgery Program, Washington Hospital Center, is clearly buoyed by the many exciting developments in prostate cancer treatment and the increasingly early detection of this second-most prevalent male cancer. “In the past five years, when the cancer is caught early, we’ve had a growing array of treatment options,” he exults. “Which are right for a given patient depends not only on PSA and Gleason scores, but also on life expectancy, the patient’s risk tolerance and other factors.”

Prognostic Nomograms

Sophisticated software tools are helping permit more nuanced treatment decisions. A prognostic tool developed by Memorial Sloan-Kettering Cancer Center analyzes PSA values, biopsy pathology data, hormone and radiation information to predict the disease course, and the likelihood of indolent versus aggressive prostate cancer.

Robotic Surgery Cuts Morbidity

Dr. Hwang observes, “A 2010 New England Journal of Medicine article concluded that, when patients have less than a 15-year life expectancy, we can use surveillance unless the cancer is aggressive. However, there’s an ongoing debate about the best treatment for younger men with aggressive disease but no significant co-morbidity. Most urologists believe that surgery offers the best chance of a cure.”

Increasing expertise in robotic-assisted prostatectomies is thankfully cutting the risk of life-altering side effects such as incontinence and impotence. Dr. Hwang notes, “The risk of severe incontinence is less than 1% at centers proficient in robotic procedures, compared to 10% with open procedures. Our center also has been able to reduce erectile dysfunction (ED) rates to about 15%, vs. 50% with an open procedure. It’s not the approach per se, but the doctor’s and the center’s experience. I believe robotic surgery will provide more consistent results.”

More Targeted Radiotherapies

Radiotherapy has also witnessed tremendous advances. “Proton beam, IMRT and cyberknife all decrease the amount of radiation scatter and the effects on surrounding tissue, providing highly precise radiotargeting,” comments Dr. Hwang. “Brachytherapy is also effective for early stage cancer, with a low risk of incontinence but a 15 to 20% risk of ED. Also, we’re now trying focal cryotherapy, targeting only sections that demonstrated cancer on biopsy. Preliminary results show that this therapy is effective for patients with early stage cancer, but we don’t yet have long term data.”

Pharmacotherapy Options Exploding

Pharmaceutical options to treat prostate cancer or its side effects have recently exploded, including:

• Provenge, an autologous cellular immunotherapy, used when cancer spreads beyond the prostate and hormone therapy is ineffective.
• Jevtana, which treats patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with docetaxel.
• Zytiga, which inhibits the CYP17 enzyme to decrease testosterone production and prevent bone damage.
• Xgeva, which delays the spread to bones and reduces fracture risk.
• Cabozantinib, an experimental drug that may eradicate bone metastases.

“We’re in an exciting phase where we have new options,” exclaims Dr. Hwang. “It appears that we can increase life expectancy by up to a year; however, the best sequence of medications has not yet been determined.” Not surprisingly, these therapies can cost up to $100k for a course of treatment.

Breast Cancer: More Complex Diagnosis and Treatment Options

Theodore Tsangaris, M.D., chief of Breast Surgery and director of the Johns Hopkins Comprehensive Breast Center, also expresses optimism when discussing breast cancer diagnosis and treatment advances.

Diagnostics More Complex

The key to early detection is still a screening mammogram,” he says. “All women aged 40 and older should still get them each year.”

Dr. Tsangaris adds, “Breast MRI can lengthen the diagnosis period and make it more complex, but it provides better outcomes for women in appropriate situations. And the days of finding breast cancer through an excisional biopsy are over. A core biopsy done by a breast imager is the right thing to do. As a result, I now see most of my patients after they’ve been diagnosed. Faster is not always better.”

Mastectomies Resurging

A lumpectomy repeatedly has been proven to be the right approach for most women with breast cancer. When combined with radiation therapy, it’s comparable to a mastectomy except in two situations – where the cancer is too large relative to the size of the breast and when multiple lesions exist.

“Nonetheless, mastectomies are making a bit of a comeback,” Dr. Tsangaris observes. “As long as the woman has thought about it carefully, I support her decision. However, if she opts to have a mastectomy, I often encourage her to get reconstruction. A 50 year old woman likely will live at least another 25 years, and an artificial prosthesis impacts many activities, not just her sexuality.”

Breast reconstruction techniques have improved dramatically. In addition to the traditional implants, new approaches include tissue taken from the midriff, back or inner thigh. Breast surgeons can now set up the plastic surgeon by doing a friendly mastectomy that can include skin sparing and even nipple sparing approaches. “Believe it or not, we can make the breast look as good, if not better, than before,” says Dr. Tsangaris. “However, we can’t preserve breast sensation, which is important to many women.”

Dr. Tsangaris is a supporter of the sentinel lymph node procedure in women with early stage breast cancer. Even when the sentinel lymph nodes are positive, new data suggests that the remaining lymph nodes do not have to be removed.

Adjuvant Therapies Undergoing Dramatic Change

The many new developments in chemotherapy and radiation therapy make this an exciting field. In radiation therapy, the standard regimen of six weeks of radiation to the whole breast, followed by radiation targeted to the cancer site, is changing. Doctors are exploring options that include:

• Radiation targeting only the lesion
• Cutting radiation to three weeks or even one week
• Avoiding external beam radiation

Dr. Tsangaris concludes, “The good news is that we’re having a more positive impact on the disease but less of a negative impact on patients’ lives. Nonetheless, selecting the right treatment option is more complex; we need to avoid rushing into a specific treatment plan until we’ve thoroughly assessed all of a patient’s options.”

Blood Cancers: Molecular Advances Stratify Treatment

Major breakthroughs also abound in the treatment of leukemias and other blood cancers. Maria Baer, M.D., director of Hematologic Malignancies at the University of Maryland Greenebaum Cancer Center, describes the progress being made in Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome and Myeloproliferative Neoplasms (MPNs). “We are now using both chromosome and molecular analysis to stratify treatment and develop targeted therapies,” she notes.

ALL and AML – Inhibiting Metabolic Abnormalities Improves Outcomes

“Doctors have long known how to detect chromosome abnormalities, but with our newer ability to detect molecular abnormalities, we can better predict how patients will respond to chemotherapy and who will benefit from bone marrow transplants. We can also incorporate targeted therapies,” says Dr. Baer. “For example, adults with ALL typically have responded less well to treatment than children, but the addition of Bcr-Abl inhibitors such as Gleevec, originally developed for chronic myelogenous leukemia (CML), to chemotherapy regimens significantly improves outcomes for patients with Philadelphia chromosome-positive ALL.”

Likewise, there is new hope for the 30% of AML patients who have a mutation of the FLT3 gene. These patients have typically responded poorly to therapy, but an ongoing international clinical trial is testing a FLT3 inhibitor in conjunction with chemotherapy. “Some patients had normal chromosomes in their leukemia cells, but still didn’t respond well to treatment,” observes Dr. Baer. “Now, we can detect molecular abnormalities in these patients’ leukemia cells and use the information to better tailor our treatment.”

She continues, “Older patients typically don’t respond as well to treatment and don’t stay in remission as long as younger patients. Using chromosome and molecular data, we can better identify patients who will do better with treatment using new approaches, without a lengthy hospital stay, while others may benefit from chemotherapy and a reduced intensity transplant approach. We are also testing a vaccine against a protein expressed in most patients’ AML cells.”

Myelodysplastic Syndromes (MDS)

Until the past decade, there were no treatments to prevent 25% of patients with MDS from progressing to AML. Since that time, several efficacious, FDA-approved treatments have become available, including the demethylating agents azacitidine and decitabine. They can significantly increase response rates, improve quality of life, reduce risk of leukemic transformation, and improve survival. Current clinical trials are testing several new drugs and drug combinations to further improve outcomes.

Myeloproliferative Neoplasms (MPN)

These diseases include myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET). Doctors recently discovered that these patients’ cells often have a mutation of the JAK2 gene, causing the abnormal proliferation. Several different JAK2 inhibitors are in clinical trials. In MF, these have been effective in shrinking the spleen and improving patient well-being; newer JAK2 inhibitors may also improve anemia.

Dr. Baer ends by noting, ‘There has been a quantum leap in treating these diseases. The tremendous discoveries with regard to their molecular pathogenesis are being translated into new treatments. CML used to be lethal unless a bone marrow transplant could be performed, but since the advent of Gleevec and other BCR-ABL inhibitors, it is now the model of success in modern oncology.”

Jonathan J. Hwang, M.D., a national expert in robotic surgery, is the director of the new Robotic Surgery Program at Washington Hospital Center.

Maria R. Baer, M.D., is professor of Medicine and Molecular Medicine at the University of Maryland School of Medicine and director, Hematologic Malignancies.

Theodore N. Tsangaris, M.D., F.A.C.S., is associate professor of Surgery, chief of Breast Surgery, Division of Surgical Oncology and director, Johns Hopkins Comprehensive Breast Center

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